Effects of Long-Term Temozolomide Treatment on Glioblastoma and Astrocytoma WHO Grade 4 Stem-like Cells

Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse.     

The machine breakdown paradox: How random shifts in the production rate may increase company profits

The causes and effects of machine breakdowns have frequently been investigated in the past. One popular stream of research studies technical errors in production and analyzes their impact on the inventory policy of the company. In this paper, we show that random shifts in the production rate of a machine, which may occur, for example, due to technical defects, may lead to a reduction in total cost and therewith to an increase in profit. This obvious paradox may lead to situations where it is economically rational for the company to sustain a technically inefficient situation, or even to take measures to intentionally induce a shift in the production rate, for example by damaging the machine on purpose. In this paper, we illustrate this paradox by referring to an existing inventory model, and trace it back to common assumptions made in the literature.     

Gesundheitsinformationen im Internet

Electronic Health (E-Health) increasingly strives to provide health information and services to healthcare stakeholders (e.g., insurances, physicians, hospital and patient alliances, self-help groups) via the Internet, and to actively involve patients in their care. One major chance for these participatory healthcare and patient-oriented approaches that integrate patients in healthcare are the phenomena and ideas associated with providing information and healthcare on the Internet. This paper examines the existing body of knowledge on online health information and explores the current state of research through a review of literature by classifying articles published between the last two decades in IS, BISE, and health domain-specific journals as well as a review of past and current BMBF-, DFG-, and EU-funded research projects in this field. The fundamental categories of the analysis represent the stakeholders in the healthcare sector, the connecting information flows, the information-transferring technological applications, as well as the categories of the TEMPEST model. Amongst others, the results show that most of the analyzed papers discuss conventional, transactional E-Health applications. Within the TEMPEST model the technological category has the largest share of all categories. Based on these findings, causes and future research fields are discussed.     

On the relationship between lateralized brain function and orienting asymmetries: Correction to Teufel et al. (2010).

Reports an error in On the relationship between lateralized brain function and orienting asymmetries by Christoph Teufel, Asif A. Ghazanfar and Julia Fischer (Behavioral Neuroscience, 2010[Aug], Vol 124[4], 437-445). In the article, we wrote that “the likelihood of obtaining at least one significant result at p n. The probability of obtaining at least one significant result is therefore 1 — (1— α)n. (The following abstract of the original article appeared in record 2010-16138-001.) Hemispheric specializations for language perception constitute one of the classic topic in cognitive neuroscience. Evidence has accumulated to suggest that lateralized acoustic processing is not restricted to humans but is also found in numerous animal species. One of the methods used to track such lateralization is the orienting-asymmetry paradigm, a simple, noninvasive means to study lateralization that has been applied to a range of different species ranging from harpy eagles to humans. Here we summarize and compare the results of studies employing the orienting-asymmetry paradigm, showing that these studies yield largely inconsistent results. We critically discuss the methodology's implicit assumptions and conclude that the empirical inconsistencies produced by the orienting-asymmetry paradigm, and the lack of sufficient evidence supporting the paradigm's underlying assumptions, warrant serious caution when interpreting results obtained by the method. Nontrivial interpretations of orienting-asymmetry results will require a much better understanding of how lateralized brain functions interact with overt behaviors. (PsycINFO Database Record (c) 2011 APA, all rights reserved)