Stochastic time-concentration activity models for cytotoxicity in 3D brain cell cultures.

BACKGROUND: In vitro aggregating brain cell cultures containing all types of brain cells have been shown to be useful for neurotoxicological investigations. The cultures are used for the detection of nervous system-specific effects of compounds by measuring multiple endpoints, including changes in enzyme activities. Concentration-dependent neurotoxicity is determined at several time points. METHODS: A Markov model was set up to describe the dynamics of brain cell populations exposed to potentially neurotoxic compounds. Brain cells were assumed to be either in a healthy or stressed state, with only stressed cells being susceptible to cell death. Cells may have switched between these states or died with concentration-dependent transition rates. Since cell numbers were not directly measurable, intracellular lactate dehydrogenase (LDH) activity was used as a surrogate. Assuming that changes in cell numbers are proportional to changes in intracellular LDH activity, stochastic enzyme activity models were derived. Maximum likelihood and least squares regression techniques were applied for estimation of the transition rates. Likelihood ratio tests were performed to test hypotheses about the transition rates. Simulation studies were used to investigate the performance of the transition rate estimators and to analyze the error rates of the likelihood ratio tests. The stochastic time-concentration activity model was applied to intracellular LDH activity measurements after 7 and 14 days of continuous exposure to propofol. The model describes transitions from healthy to stressed cells and from stressed cells to death. RESULTS: The model predicted that propofol would affect stressed cells more than healthy cells. Increasing propofol concentration from 10 to 100 μM reduced the mean waiting time for transition to the stressed state by 50%, from 14 to 7 days, whereas the mean duration to cellular death reduced more dramatically from 2.7 days to 6.5 hours. CONCLUSION: The proposed stochastic modeling approach can be used to discriminate between different biological hypotheses regarding the effect of a compound on the transition rates. The effects of different compounds on the transition rate estimates can be quantitatively compared. Data can be extrapolated at late measurement time points to investigate whether costs and time-consuming long-term experiments could possibly be eliminated

Simulating and reporting frequentist operating characteristics of clinical trials that borrow external information: Towards a fair comparison in case of one‐arm and hybrid control two‐arm trials

Borrowing information from historical or external data to inform inference in a current trial is an expanding field in the era of precision medicine, where trials are often performed in small patient cohorts for practical or ethical reasons. Even though methods proposed for borrowing from external data are mainly based on Bayesian approaches that incorporate external information into the prior for the current analysis, frequentist operating characteristics of the analysis strategy are often of interest. In particular, type I error rate and power at a prespecified point alternative are the focus. We propose a procedure to investigate and report the frequentist operating characteristics in this context. The approach evaluates type I error rate of the test with borrowing from external data and calibrates the test without borrowing to this type I error rate. On this basis, a fair comparison of power between the test with and without borrowing is achieved. We show that no power gains are possible in one‐sided one‐arm and two‐arm hybrid control trials with normal endpoint, a finding proven in general before. We prove that in one‐arm fixed‐borrowing situations, unconditional power (i.e., when external data is random) is reduced. The Empirical Bayes power prior approach that dynamically borrows information according to the similarity of current and external data avoids the exorbitant type I error inflation occurring with fixed borrowing. In the hybrid control two‐arm trial we observe power reductions as compared to the test calibrated to borrowing that increase when considering unconditional power

Zur Entwicklung soziologischer Forschung

In diesem Beitrag wird untersucht, inwieweit sich einige Charakteristika der Aufsätze in der Kölner Zeitschrift für Soziologie und Sozialpsychologie sowie der Zeitschrift für Soziologie in den letzten vierzig Jahren verändert haben. Hierzu wurden die dort publizierten Beiträge für den Zeitraum von 1970 bis 2010 inhaltsanalytisch ausgewertet. Als Ergebnis lassen sich fünf Entwicklungen festhalten: Erstens zeigt sich eine klare Tendenz weg von der Alleinautorenschaft von Beiträgen und hin zu Publikationen von (kleineren) Forschungsteams. Zweitens steigt in den Fachzeitschriften der Anteil von Autorinnen langsam an. Soziologie ist drittens zumindest in den Fachjournalen immer mehr eine empirische Wissenschaft, wobei viertens qualitative Beiträge kaum eine Rolle spielen und quantitative Analysen eindeutig dominieren. Fünftens schließlich basieren diese Analysen immer mehr auf allgemein zugänglichen Datenbeständen und nicht mehr auf Primärerhebungen. Die Ergebnisse zeigen, dass die im universitären Alltag an Bedeutung gewinnenden Anreizsysteme nicht immer die richtigen Zielgrößen der Wissenschaft unterstützen.    The paper examines the extent to which some characteristics of the contributions in the leading two German sociological journals, the Kölner Zeitschrift für Soziologie und Sozialpsychologie and the Zeitschrift für Soziologie have changed over the last 40 years. Using quantitative content analyses first a clear trend is shown, that the numbers of articles written by more than one author is increasing. Secondly, the publications are no more male dominated, the proportion of female authors increases – even though slowly. Sociology is thirdly, at least in these journals more and more an empirical science. Fourthly, qualitative contributions play only a minor role, quantitative research clearly dominates. Finally, the papers use more and more publicly available data and are not based on own data collection. These results show that the universities incentive system does not always support the important targets for scientific progress.&nbsp

Mongolia image realization aspects in the Russian internet-discourse

Статья посвящена исследованию лексической репрезентации образа Монголиив Интернет-дискурсе. Данная тема особо актуальна в современном мультикультурном обществе, когда основным средством общения между людьми становится Интернет. Цель статьи: выявить структуру образа Монголии в Интернет-дискурсе. Основные методы исследования: теоретический анализ научной литературы и лингвистический анализ текстов. В начале мы исследуем новостной субдискурс, далее - специфику туристического. В результате исследования мы делаем выводы о роли глаголов в текстах новостей и прилагательных - в описаниях Монголии на сайтах туристических компаний. Currently, we live in an open multicultural society, so we have to understand each other. Due to the modern trend that our life is flowing in The Global Net, it becomes essential to perceive other languages' concepts that are widely presented in social nets and support their availability. The present article examines lexical representation of Mongolia image in the Internet-discourse. The main paper aim is to find out the structure of Mongolia image. The described methodology includes a theoretical analysis of researches and linguistic text analysis. Firstly, we study news subdiscourse in the Internet. Secondly, we found a specific of tourist subdiscourse. As a result, we make some conclusions about the verb role in news and adjective value in tourist subdiscourse