Temozolomide: a milestone in neuro-oncology and beyond?

Temozolomide (Temodal, Temodar), an imidazol derivative, is a second-generation alkylating agent. The orally available prodrug with the capacity of crossing the blood-brain barrier received accelerated US FDA approval in 1999. Three pivotal Phase II trials showed modest activity in the treatment of recurrent anaplastic astrocytoma glioblastoma. In 2005, the FDA and the European Agency for the Evaluation of Medicinal Products approved temozolomide for use in newly diagnosed glioblastoma, in conjunction with radiotherapy, based on an European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Phase III trial. The adverse events associated with temozolomide are mild-to-moderate and generally predictable; the most serious are noncumulative and reversible myelosuppression and, in particular, thrombocytopenia, which occurs in less than 5% of patients. Continuous temozolomide administration is associated with profound CD4-selective lymphocytopenia. Molecular studies have suggested that the benefit of temozolomide chemotherapy is restricted to patients whose tumors have a methylated methylguanine methyltransferase gene promotor and are thus unable to repair some of the chemotherapy-induced DNA damage. Temozolomide is under investigation for other disease entities, in particular lower-grade glioma, brain metastases and melanoma.

V&B celebrate building milestone

The firm celebrates the construction of new headquarters.

Stereoscopic imaging of an Earth-impacting solar coronal mass ejection: a major milestone for the STEREO mission

We present stereoscopic images of an Earth-impacting Coronal Mass Ejection (CME). The CME was imaged by the Heliospheric Imagers onboard the twin STEREO spacecraft during December 2008. The apparent acceleration of the CME is used to provide independent estimates of its speed and direction from the two spacecraft. Three distinct signatures within the CME were all found to be closely Earth-directed. At the time that the CME was predicted to pass the ACE spacecraft, in-situ observations contained a typical CME signature. At Earth, ground-based magnetometer observations showed a small but widespread sudden response to the compression of the geomagnetic cavity at CME impact. In this case, STEREO could have given warning of CME impact at least 24 hours in advance. These stereoscopic observations represent a significant milestone for the STEREO mission and have significant potential for improving operational space weather forecasting.

Comparative Analysis of Existing Guidelines for Gender-Fair Language within the ITN LCG Network. ITN-LCG, Workpackage B: Report on Milestone 1

Guidelines for a gender-fair use of the languages represented in the ITN LCG network were analyzed comparatively for specific criteria. All institutional or governmental guidelines aim at attenuating male-biased representations that are brought about by certain grammatical structures of the respective language. These guidelines primarily focus on the use of masculine forms as generics because they reduce the visibility of women in language. The comparison shows that guidelines for English, a language without grammatical gender, emphasize neutralization as a means of referring to both sexes. This differs from grammatical gender languages, such as German and Italian, in which feminine-masculine word-pairs are recommended in order to avoid the masculine bias. The guidelines all aim to promote the formulation of comprehensive and readable texts that are free of discrimination.

Assessing the effectiveness of milestone budgeting.

Item 1005-C

Systemic monocyte activation levels and developmental milestone attainment in HIV-infected infants initiating antiretroviral therapy

Thesis (Master's)--University of Washington, 2016-06

Grounded theory, a kvalitatív kutatás klasszikus mérföldköve (Grounded theory, the classic milestone of qualitative research)

A grounded theory olyan kutatási módszer, ahol az elmélet az empirikus adatokból fejlődik ki és abban gyökerezik (Glaser - Strauss, 1967). Annak ellenére, hogy a módszer nemzetközileg rendkívül népszerű, a grounded theory nem igazán vert gyökeret a hazai menedzsment- és marketingkutatás talajában. A cikk célja a grounded theory kulcsfontosságú mozzanatainak bemutatása és a módszer népszerűsítése. / === / Grounded theory is a research method in which theory emerges from the data and is grounded in it (Glaser - Strauss, 1967). Despite the international popularity of the method, the grounded theory unfortunately hasn't taken roots in the Hungarian management and marketing research fields. The purpose of this article is to highlight some features and key points of the method and to popularize it among researchers.

CIL 5.8045 – Milestone

Photographs and notes by A.E. Gordon

CIL 3.5992 – Milestone

Photograph and translation