Characterization of the 9L gliosarcoma implanted in the Fischer rat: an orthotopic model for a grade IV brain tumor.

Among rodent models for brain tumors, the 9L gliosarcoma is one of the most widely used. Our 9L-European Synchrotron Radiation Facility (ESRF) model was developed from cells acquired at the Brookhaven National Laboratory (NY, USA) in 1997 and implanted in the right caudate nucleus of syngeneic Fisher rats. It has been largely used by the user community of the ESRF during the last decade, for imaging, radiotherapy, and chemotherapy, including innovative treatments based on particular irradiation techniques and/or use of new drugs. This work presents a detailed study of its characteristics, assessed by magnetic resonance imaging (MRI), histology, immunohistochemistry, and cytogenetic analysis. The data used for this work were from rats sampled in six experiments carried out over a 3-year period in our lab (total number of rats = 142). The 9L-ESRF tumors were induced by a stereotactic inoculation of 10(4) 9L cells in the right caudate nucleus of the brain. The assessment of vascular parameters was performed by MRI (blood volume fraction and vascular size index) and by immunostaining of vessels (rat endothelial cell antigen-1 and type IV collagen). Immunohistochemistry and regular histology were used to describe features such as tumor cell infiltration, necrosis area, nuclear pleomorphism, cellularity, mitotic characteristics, leukocytic infiltration, proliferation, and inflammation. Moreover, for each of the six experiments, the survival of the animals was assessed and related to the tumor growth observed by MRI or histology. Additionally, the cytogenetic status of the 9L cells used at ESRF lab was investigated by comparative genomics hybridization analysis. Finally, the response of the 9L-ESRF tumor to radiotherapy was estimated by plotting the survival curves after irradiation. The median survival time of 9L-ESRF tumor-bearing rats was highly reproducible (19-20 days). The 9L-ESRF tumors presented a quasi-exponential growth, were highly vascularized with a high cellular density and a high proliferative index, accompanied by signs of inflammatory responses. We also report an infiltrative pattern which is poorly observed on conventional 9 L tumor. The 9L-ESRF cells presented some cytogenetic specificities such as altered regions including CDK4, CDKN2A, CDKN2B, and MDM2 genes. Finally, the lifespan of 9L-ESRF tumor-bearing rats was enhanced up to 28, 35, and 45 days for single doses of 10, 20, and 2 × 20 Gy, respectively. First, this report describes an animal model that is used worldwide. Second, we describe few features typical of our model if compared to other 9L models worldwide. Altogether, the 9L-ESRF tumor model presents characteristics close to the human high-grade gliomas such as high proliferative capability, high vascularization and a high infiltrative pattern. Its response to radiotherapy demonstrates its potential as a tool for innovative radiotherapy protocols.

Habitat-dependent geographical variation in ontogenetic allometry of the shiner perch Cymatogaster aggregata Gibbons (Teleostei: Embiotocidae)

Studies of intraspecific morphological variation in fishes have traditionally focused on freshwater rather than marine species. In addition, such studies typically focus on adults, although causes and intensities of selective pressures most likely vary through an individual’s lifetime. In this study, body and head shape of a marine species, shiner perch Cymatogaster aggregata Gibbons were compared among localities along the Pacific Northwest coast of North America. Evidence was found for intraspecific variation in ontogenetic allometry, and for a closer correlation of body shape with environment rather than geographical proximity. This correlation with environment was more evident in younger fish, thereby demonstrating the importance of analysing multiple life stages. A common garden experiment suggests both environmental and genetic bases for the observed differences. Recognizing intraspecific ecomorphological complexity and its specificity to habitat and/or life stage can have important consequences for understanding the role of local adaptation and population dynamics in macroecology.

Untersuchung ob die bürgerliche Freiheit den Juden zu gestatten sei : ... Herrn Freiherrn von Werder zugeeignet

von Friedrich Traugott Hartmann

Beitrag zum Forschen nach Licht und Recht, veranlasset durch ein Schreiben an Moses Mendelssohn, unter diesem Titel

von Otto Justus Basilius Hesse

Beitrag zur Geschichte der Verfolgung der Juden im 19ten Jahrhundert durch Schriftsteller : ein Sendschreiben an die Frau Kammerherrin von der Recke, geb. Gräfin v. Medem

von David Friedländer

Discorsi Ebraici di tolleranza e felicità ; con le note del traduttore

diretti da Naftali Herz Weisel agli Ebrei diomanti ne' dominij dell' ... imperatore Guiseppe II. Trad. di Elia Morpurgo

Nachrichten von dem Leben, Schicksalen und Bekehrung Friedrich Albrecht Augusti, eines vormaligen jüdischen Rabbi, und nachherigen drei und funfzigjährigen christlichen Lehrers

aufgesetzet von Ernst Friedrich Anton Augusti

The mini-clinical evaluation exercise during medical clerkships: are learning needs and learning goals aligned?

OBJECTIVES The generation of learning goals (LGs) that are aligned with learning needs (LNs) is one of the main purposes of formative workplace-based assessment. In this study, we aimed to analyse how often trainer–student pairs identified corresponding LNs in mini-clinical evaluation exercise (mini-CEX) encounters and to what degree these LNs aligned with recorded LGs, taking into account the social environment (e.g. clinic size) in which the mini-CEX was conducted. METHODS Retrospective analyses of adapted mini-CEX forms (trainers’ and students’ assessments) completed by all Year 4 medical students during clerkships were performed. Learning needs were defined by the lowest score(s) assigned to one or more of the mini-CEX domains. Learning goals were categorised qualitatively according to their correspondence with the six mini-CEX domains (e.g. history taking, professionalism). Following descriptive analyses of LNs and LGs, multi-level logistic regression models were used to predict LGs by identified LNs and social context variables. RESULTS A total of 512 trainers and 165 students conducted 1783 mini-CEXs (98% completion rate). Concordantly, trainer–student pairs most often identified LNs in the domains of ‘clinical reasoning’ (23% of 1167 complete forms), ‘organisation/efficiency’ (20%) and ‘physical examination’ (20%). At least one ‘defined’ LG was noted on 313 student forms (18% of 1710). Of the 446 LGs noted in total, the most frequently noted were ‘physical examination’ (49%) and ‘history taking’ (21%). Corresponding LNs as well as social context factors (e.g. clinic size) were found to be predictors of these LGs. CONCLUSIONS Although trainer–student pairs often agreed in the LNs they identified, many assessments did not result in aligned LGs. The sparseness of LGs, their dependency on social context and their partial non-alignment with students’ LNs raise questions about how the full potential of the mini-CEX as not only a ‘diagnostic’ but also an ‘educational’ tool can be exploited.