Bouleversement de la conscience historique

La situation des nouveaux Lander allemands, où la réorganisation de l’enseignement de l’histoire s’est effectuée par imposition des modèles importés de l’Allemagne de l’Ouest, présente un caractère exceptionnel en permettant une comparaison entre deux formes distinctes de structuration de l’histoire et de la conscience historique à l’intérieur d’une même nation. Il en résulte une occasion unique d’approfondir les mécanismes de constitution de cette conscience chez l’individu, et par là d’éclaircir les conditions de formation de l’histoire comme discipline

TLD-1, a novel liposomal doxorubicin, in patients with advanced solid tumors: Dose escalation and expansion part of a multicenter open-label phase I trial (SAKK 65/16).

BACKGROUND TLD-1 is a novel liposomal doxorubicin that compared favorably to conventional doxorubicin liposomal formulations in preclinical models. This phase I first-in-human study aimed to define the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary activity of TLD-1 in patients with advanced solid tumors. PATIENTS AND METHODS We recruited patients with advanced solid tumors who failed standard therapy and received up to 3 prior lines of palliative systemic chemotherapy. TLD-1 was administered intravenously every 3 weeks up to a maximum of 9 cycles (6 for patients with prior anthracyclines) from a starting dose of 10 mg/m2, according to an accelerated titration design followed by a modified continual reassessment method. RESULTS 30 patients were enrolled between November 2018 and May 2021. No dose-limiting toxicities (DLT) were observed. Maximum administered dose of TLD-1 was 45 mg/m2, RP2D was defined at 40 mg/m2. Most frequent treatment-related adverse events (TRAE) of any grade included palmar-plantar erythrodysesthesia (PPE) (50% of patients), oral mucositis (50%), fatigue (30%) and skin rash (26.7%). Most common G3 TRAE included PPE in 4 patients (13.3%) and oral mucositis in 2 (6.7%). Overall objective response rate was 10% in the whole population and 23.1% among 13 patients with breast cancer; median time-to-treatment failure was 2.7 months. TLD-1 exhibit linear pharmacokinetics, with a median terminal half-life of 95 h. CONCLUSIONS The new liposomal doxorubicin formulation TLD-1 showed a favourable safety profile and antitumor activity, particularly in breast cancer. RP2D was defined at 40 mg/m2 administered every 3 weeks. (NCT03387917)

Smart Fertilization for Tailored Valorization of Tall Wheatgrass Biomass

The perennial grass species Agropyron elongatum, commonly named "tall wheatgrass" (Poacea), has been gaining attention in recent years for its potential as a bioenergy and biorefinery feedstock. A. elongatum is native to southern Europe and Asia Minor, and was introduced to other places in the world as an energy crop, fodder and reclamation grass also marginal sandy soils. Therefore, A. elongatum is an attractive alternative to traditional energy crops such as corn and sugarcane. Improved biomass yield by targeted fertilization in sand using alternative nutrient carriers such as digestate has already been successfully demonstrated earlier and was transferred to the present investigation. One of the key benefits of using A. elongatum for energy and biorefinery applications is its high cellulose content and processability. Depending on the pre-treatment (alkaline or acidic) of the bulk, more than 75% crystalline cellulose and more than 25% lignin can be obtained. As demonstrated earlier, acid pre-treatment even allowed for a direct conversion of 25% of the cellulose into glucose without the need for enzymatic digestion