Diels-Alder-Reaktionen fluorierter Dienophile und Diene und ihr Einsatz in Synthesen fluorierter Steroidanaloga und Cantharidine

An der Synthese von fluororganischen Verbindungen besteht ein großes Interesse, seitdem man erkannt hat, daß die biologische Aktivität von Wirkstoffen durch die Einführung eines Fluorsubstituenten verändert und in vielen Fällen deutlich gesteigert werden kann. Im ersten Teil der Arbeit werden Diels-Alder-Reaktionen a-Fluor-a, ß-ungesättigter Carbonylverbindungen mit Cyclopentadien unter verschiedenen Reaktionsbedingungen systematisch untersucht und mit den Reaktionen der fluorfreien Stammverbindungen verglichen. Anschließend werden Synthesen verschiedener fluorierter Steroid-Analoga bzw. von Bausteinen hierfür beschrieben. Bisherige Wege basierten auf der Einführung von Fluor in das fertige Steroidgerüst. In dieser Arbeit wird ausgehend von fluorierten Synthesbausteinen das Steroidgerüst durch Diels-Alder-Reaktionen als Schlüsselschritt aufgebaut. Der dritte Teil der Arbeit befaßt sich mit der Darstellung fluorierter Cantharidin-Analoga. Cantharadin ist ein natürlich vorkommendes Toxin mit vielfältiger biologischer, u.a. antitumoraler Aktivität. Diels-Alder-Reaktionen führen auch hier zu den Zielmolekülen

Monitoring daily physical activity of upper extremity in young and adolescent boys with Duchenne muscular dystrophy:A pilot study

Introduction Accelerometry of the upper extremity (UE) potentially provides information on the extent of activities in daily life in patients with Duchenne muscular dystrophy (DMD). The objective of this study is to evaluate the validity of home measurements of UE accelerometry. Methods This was a cross-sectional study in 16 patients with DMD (aged 7-17 years). Patients were monitored for 1 to 3 days with two accelerometers on the UE and one accelerometer on the wheelchair. Results The mean intensity of activity and the mean frequency of transfers of arm elevation from low to middle were approximately twofold higher in patients with a Brooke scale score of 1 or 2 than in patients with a Brooke scale score of 3 or 4. Correlations with the Performance of Upper Limb scale score were high for intensity and for the total frequency of arm elevations per hour. Discussion Intensity, percentage of time in middle orientation, and frequency of transfers of the upper arm correlated well with functional measurements

Of autoregressive continuous time model parameters estimation

This article revisits a sequential approach to the estimation of the parameter in a first-order autoregressive model (AR(1)) with continuous time. There is provided a numerical study to get a results of sequential estimations of the parameter in first-order autoregressive model with continuous time and is computed a stopping rule and the optimal time of observations. Also there is provided a comparing analysis of estimation results with using the sequential approach both the optimal time of observations

PND44 Eliciting Patients’ Preferences for Epilepsy Diagnostics: A Discrete Choice Experiment

Background: Diagnosing epilepsy is a lengthy and burdensome process for patients and their family. Although the need for a more patient-centered approach in clinical practice is widely acknowledged, empirical evidence regarding patient preferences for diagnostic modalities in epilepsy is missing. The objectives of this study were 1) to identify to what extent important attributes of diagnostic procedures in epilepsy affect preferences for a procedure, 2) to determine the relative importance of these attributes, and 3) to calculate overall utility scores for routine electroencephalography (EEG) and magnetoencephalography (MEG) recordings. Methods: A discrete choice experiment was performed to determine patients' preferences, which involved presentation of pairwise choice tasks regarding hypothetical scenarios. Scenarios varied along six attributes: "way of measuring brain activity", "duration", "freedom of movement", "travel time", "type of additional examination", and "chance of additional examination". Choice tasks were constructed using a statistically efficient design, and the questionnaire contained 15 unique unlabeled choice tasks. Mixed multinomial logistic regression was used to estimate patients' preferences. Results: A total of 289 questionnaires were included in the analysis. McFadden's pseudo R-2 showed a model fit of 0.28, and all attributes were statistically significant. Heterogeneity in preferences was present for all attributes. "Freedom of movement" and "Chance of additional examination" were perceived as the most important attributes. Overall utility scores did not substantially differ between routine EEG and MEG. Conclusion: This study suggests that the identified attributes are important in determining patients' preference for epilepsy diagnostics. It can be concluded that MEG is not necessarily more patient-friendly than a routine EEG in primary diagnostics and, regarding additional diagnostics, patients have a strong preference for long-term 24-h EEG over EEG after sleep deprivation. Furthermore, barring substantial heterogeneity within the parameters in mind, our study suggests that it is important to take individual preferences into account in medical decision-making. (C) 2013 Elsevier Inc. All rights reserved

RTEL1 contributes to DNA replication and repair and telomere maintenance

Telomere maintenance and DNA repair are important processes that protect the genome against instability. mRtel1, an essential helicase, is a dominant factor setting telomere length in mice. In addition, mRtel1 is involved in DNA double-strand break repair. The role of mRtel1 in telomere maintenance and genome stability is poorly understood. Therefore we used mRtel1-deficient mouse embryonic stem cells to examine the function of mRtel1 in replication, DNA repair, recombination, and telomere maintenance. mRtel1-deficient mouse embryonic stem cells showed sensitivity to a range of DNA-damaging agents, highlighting its role in replication and genome maintenance. Deletion of mRtel1 increased the frequency of sister chromatid exchange events and suppressed gene replacement, demonstrating the involvement of the protein in homologous recombination. mRtel1 localized transiently at telomeres and is needed for efficient telomere replication. Of interest, in the absence of mRtel1, telomeres in embryonic stem cells appeared relatively stable in length, suggesting that mRtel1 is required to allow extension by telomerase. We propose that mRtel1 is a key protein for DNA replication, recombination, and repair and efficient elongation of telomeres by telomerase

Capacity building improve Malaysia's inspection and monitoring system for aquaculture and fishery products

The project aimed to help build a credible inspection and monitoring system that can guarantee safe quality products of Ministry of Health (MoH) and Department of Fisheries (DoF) by upgrading the analytical capacity of the laboratory staff directly involved in the analysis and detection of forbidden substances. Two training courses were implemented in 2011 in the Bio Security Centre in Kuantan, Malaysia. The first training course on 'Marine lipophilic toxins using LC-MS/MS has been implemented in June and the second training course on on Stilbenes and Nitroïmidazoles sample preparation and analysis with LC-MS/MS equipment was implemented in November, 2011. Through this knowledge transfer and laboratory enhancement the project contributed the laboratory's process towards getting accreditation under ISO 17025. The courses were implemented in partnership by Wageningen UR Institute of Food Safety (RIKILT) and Wageningen UR Centre for Development Innovation (CDI). Report no. CDI-12-00

Acute Community-Acquired Diarrhea Requiring Hospital Admission in Swiss Children

In order to ascertain the prevalence of agents that cause childhood diarrheal illness, stool specimens of 312 consecutive children with community-acquired diarrhea requiring admission were evaluated. Pathogens were detected in 166 (53%) of the 312 children (≥2 pathogens in 28 children): Rotavirus (n=75), Salmonella spp. (n=37), Campylobacter spp. (n=24), Shigella spp. (n=5), Giardia spp. (n=4), Yersinia spp. (n=2), Aeromonas spp. (n=15), Cryptosporidium (n=15), enteropathogenic Escherichia coli (n=13), enterotoxigenic E. coli (n=7), and enterohemorrhagic E. coli (n=5). In conclusion, acute childhood diarrheal illness pathogens, such as Aeromonas, Cryptosporidium, and diarrheagenic E. coli, account for a large proportion of patients with a microbiologically positive stool specime

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set : translation and cross-cultural adaptation into 15 languages

Introduction: The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. Methods: Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. Results: The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness. Discussion: This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures