The development and evaluation of procedures for the synthesis of phenolic ethers by Baeyer-Villiger oxidation

A novel preparative method has been discovered in our laboratories which produces hydroxy-substituted phenolic ethers in a simple one-pot process. Initially it was found that 4-hydroxyacetophenone, when oxidized in the presence of ammonium peroxydisulfate and concentrated sulfuric acid in methanol, resulted in 4- methoxyphenol as product in high yield. Being novel, no information about the method was available in the literature, and hence it was our task to study the reaction more extensively. The scope of the reaction was investigated in that different reagents and substrates, as well as alternative oxidants, catalysts and alcohols (or reagents which may be envisaged to behave similarly to alcohols) were used. The studies showed that 4- hydroxy-substituted benzaldehyde and acetophenone, vanillin, fuchsones and stilbenequinones as substrates all successfully afforded the phenolic ether. Other oxidants such as hydrogen peroxide, sodium perborate etc. also afforded the phenolic ether but were less effective. The use of other acids than sulfuric acid resulted in comparable or lower yields of the desired phenolic ether. When the use of alcohols or similar reagents was varied, it was found that methanol, ethanol, benzyl alcohol, allyl alcohol, but-3-en-1-ol, hex-5-en-1-ol and undec-10-en-1-ol all afforded the desired ethers in significant yields. In an investigation to determine how this method may be useful for industrial applications, it was observed that compounds such as 3,5-di-tert-butyl-4-hydroxysubstituted alkenyloxy phenols, having potential application as antioxidant precursors in the polymer industry, may be prepared. Results showed that the reaction became less efficient when the alkenyl chain length was increased. The use of different acids and oxidants, the change of the oxidant:substrate ratio and the addition of a potential lanthanide catalyst did not improve the yield of the desired ether. A mechanism for the reaction was proposed which involved an initial Baeyer-Villiger oxygen insertion step to afford an ester which was hydrolysed in situ to hydroquinone. The remaining oxidant was then involved in oxidizing some of the soformed hydroquinone to benzoquinone. It was then proposed that these two compounds, i.e., hydroquinone and benzoquinone, interacted with each other in solution, forming a charge-transfer complex. According to our proposal, the carbonyl group of the benzoquinone, when complexed with hydroquinone in solution, was then attacked by nucleophilic reagents such as alcohols. Etherification hence resulted as a consequence of this attack. A statistical experimental evaluation and optimization study was then performed which led to a system that produced the phenolic ether, 4-methoxyphenol, in an 86% yield. An analysis of the effects of the reaction parameters on the reaction showed that the reaction temperature and the oxidant:substrate ratio played a major role in deciding the effectiveness of the reaction, while the amount of substrate and acidic catalyst had a much smaller influence on the ether yields

Antibiotic resistance in primary care in Austria - a systematic review of scientific and grey literature

<p>Abstract</p> <p>Background</p> <p>Antibiotic resistance is an increasing challenge for health care services worldwide. While up to 90% of antibiotics are being prescribed in the outpatient sector recommendations for the treatment of community-acquired infections are usually based on resistance findings from hospitalized patients. In context of the EU-project called "APRES - the appropriateness of prescribing antibiotic in primary health care in Europe with respect to antibiotic resistance" it was our aim to gain detailed information about the resistance data from Austria in both the scientific and the grey literature.</p> <p>Methods</p> <p>A systematic review was performed including scientific and grey literature published between 2000 and 2010. Inclusion and exclusion criteria were defined and the review process followed published recommendations.</p> <p>Results</p> <p>Seventeen scientific articles and 23 grey literature documents could be found. In contrast to the grey literature, the scientific publications describe only a small part of the resistance situation in the primary health care sector in Austria. Merely half of these publications contain data from the ambulatory sector exclusively but these data are older than ten years, are very heterogeneous concerning the observed time period, the number and origin of the isolates and the kind of bacteria analysed. The grey literature yields more comprehensive and up-to-date information of the content of interest. These sources are available in German only and are not easily accessible. The resistance situation described in the grey literature can be summarized as rather stable over the last two years. For <it>Escherichia coli </it>e.g. the highest antibiotic resistance rates can be seen with fluorochiniolones (19%) and trimethoprim/sulfamethoxazole (27%).</p> <p>Conclusion</p> <p>Comprehensive and up-to-date antibiotic resistance data of different pathogens isolated from the community level in Austria are presented. They could be found mainly in the grey literature, only few are published in peer-reviewed journals. The grey literature, therefore, is a very valuable source of relevant information. It could be speculated that the situation of published literature is similar in other countries as well.</p

Evaluation of a Respiration Rate Sensor for Recording Tidal Volume in Calves under Field Conditions

In the assessment of pulmonary function in health and disease, both respiration rate (RR) and tidal volume (Vt) are fundamental parameters of spontaneous breathing. The aim of this study was to evaluate whether an RR sensor, which was previously developed for cattle, is suitable for additional measurements of Vt in calves. This new method would offer the opportunity to measure Vt continuously in freely moving animals. To measure Vt noninvasively, the application of a Lilly-type pneumotachograph implanted in the impulse oscillometry system (IOS) was used as the gold standard method. For this purpose, we applied both measuring devices in different orders successively, for 2 days on 10 healthy calves. However, the Vt equivalent (RR sensor) could not be converted into a true volume in mL or L. For a reliable recording of the Vt equivalent, a technical revision of the RR sensor excluding artifacts is required. In conclusion, converting the pressure signal of the RR sensor into a flow equivalent, and subsequently into a volume equivalent, by a comprehensive analysis, provides the basis for further improvement of the measuring system

Computational Complexity of Synchronization under Regular Constraints

Many variations of synchronization of finite automata have been studied in the previous decades. Here, we suggest studying the question if synchronizing words exist that belong to some fixed constraint language, given by some partial finite automaton called constraint automaton. We show that this synchronization problem becomes PSPACE-complete even for some constraint automata with two states and a ternary alphabet. In addition, we characterize constraint automata with arbitrarily many states for which the constrained synchronization problem is polynomial-time solvable. We classify the complexity of the constrained synchronization problem for constraint automata with two states and two or three letters completely and lift those results to larger classes of finite automata

Sprachförderung in der beruflichen Bildung nach dem Unterrichtskonzept „Berufssprache Deutsch“

Eine durchgängige Sprachbildung und die Beschulung von Neuzugewanderten an beruflichen Schulen erst in Berufsintegrationsklassen und dann in Regelklassen erfordert die Bereitstellung angemessener Unterrichtskonzepte und -materialien. Das Unterrichtsprinzip „Berufssprache Deutsch“ erfüllt diese Forderung durch einen neuen Lehrplan und ein berufsorientiertes Sprachbildungskonzept mit Musterszenarien für unterschiedliche Ausbildungsberufe. Anhand von neu entwickelten Unterrichtsmaterialien wird in diesem Beitrag die Umsetzung dieses Konzepts anhand eines Lehrwerks für Berufsintegrationsvorklassen in Bayern veranschaulicht.Integrated language training in vocational schools and the special needs of young adults with recent migration background require adequate curricula and teaching materials. This paper presents the foundations and leading principles of a new concept for both general education as well as job-specific, vocational education and on-the-job-training: Berufssprache Deutsch (German for Professional Purposes). Its implementation is illustrated on the basis of new teaching materials for A1/A2-learners attending preliminary classes at vocational schools in Bavaria

Sprachförderung in der beruflichen Bildung nach dem Unterrichtskonzept „Berufssprache Deutsch“

Eine durchgängige Sprachbildung und die Beschulung von Neuzugewanderten an beruflichen Schulen erst in Berufsintegrationsklassen und dann in Regelklassen erfordert die Bereitstellung angemessener Unterrichtskonzepte und - materialien. Das Unterrichtsprinzip „Berufssprache Deutsch“ erfüllt diese Forderung durch einen neuen Lehrplan und ein berufsorientiertes Sprachbildungskonzept mit Musterszenarien für unterschiedliche Ausbildungsberufe. Anhand von neu entwickelten Unterrichtsmaterialien wird in diesem Beitrag die Umsetzung dieses Konzepts anhand eines Lehrwerks für Berufsintegrationsvorklassen in Bayern veranschaulicht

Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy

Background Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT. Methods Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival. Results Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model. Conclusion Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy

Fire, late frost, nun moth and drought risks in Germany's forests under climate change

Ongoing climate change affects growth and increases biotic and abiotic threats to Germany's forests. We analysed how these risks develop through the mid-century under a variety of climate change scenarios using the process-based forest model 4C. This model allows the calculation of indicators for fire danger, late frost risk for beech and oak, drought stress and nun moth risk. 4C was driven by a set of 4 simulations of future climate generated with the statistical model STARS and with 10 simulations of future climate based on EURO-CORDEX model simulations for the RCP2.6, RCP4.5 and RCP8.5 pathways. A set of about 70000 forest stands (Norway spruce, Scots pine, beech, oak, birch), based on the national forest inventory describing 98.4 % of the forest in Germany, was used together with data from a digital soil map. The changes and the range of changes were analysed by comparing results of a recent time period (1971–2005) and a scenario time period (2011–2045). All indicators showed higher risks for the scenario time period compared to the recent time period, except the late frost risk indicators, if averaged over all climate scenarios. The late frost risk for beech and oaks decreased for the main forest sites. Under recent climate conditions, the highest risk with regard to all five indicators was found to be in the Southwest Uplands and the northern part of Germany. The highest climate-induced uncertainty regarding the indicators for 2011–2045 is projected for the East Central Uplands and Northeast German Plain

Molecular Phylogenetics of Phyllanthaceae: Evidence from Plastid MatK and Nuclear PHYC Sequences

Plastid matK and a fragment of the low-copy nuclear gene PHYC were sequenced for 30 genera of Phyllanthaceae to evaluate tribal and generic delimitation. Resolution and bootstrap percentages obtained with matK are higher than that of PHYC but both regions show nearly identical phylogenetic patterns. Phylogenetic relationships inferred from the independent and combined data are congruent and differ from previous, morphology-based classifications but are highly concordant with those of the plastid gene rbcL previously published. Phyllanthaceae is monophyletic and gives rise to two well-resolved clades (T and F) that could be recognized as subfamilies. DNA sequence data for Keayodendron and Zimmermanniopsis are presented for the first time. Keayodendron is misplaced in tribe Phyllantheae and belongs to the Bridelia alliance. Zimmermanniopsis is sister to Zimmermannia. Phyllanthus and Cleistanthus are paraphyletic. Savia and Phyllanthus subgenus Kirganelia are not monophyletic.Organismic and Evolutionary Biolog

Follow-up for breast cancer - the patients' view

Background: International and national guidelines (S3 guideline) for the surveillance of post-treatment breast cancer patients recommend a clinical follow-up including routine history and physical examination and regular mammograms. The practice of a clinical follow-up has been often discussed, but has been proven not to be inferior when compared to an intensified follow-up in randomized trials. Patients and Methods: The present manuscript reports the patients' view on the basis of a survey including 2000 patients with a history of breast cancer. Results: A total of 452 patients (22.6%) answered the questionnaire. The median age was 62 years (range 23-85 years). More than 80% of the patients were disease-free at the time of the survey. The need for surveillance was affirmed by the majority of patients (>95%), and one third stated that there was a need for more technical efforts during follow-up. In contrast to the follow-up guidelines, the results of the present survey indicated that most of the regularly scheduled follow-up visits were expanded using extensive laboratory and imaging procedures. Conclusion: This survey shows that the majority of physicians obviously do not accept the present follow-up guidelines. A new surveillance study investigating the efficacy of an intensified surveillance based on the improved possibilities of modern diagnostics and endocrine, immunotherapeutic, chemotherapeutic and interventional treatment options is warranted