Von der RAG zum Staatsministerium für Landesentwicklung und Umweltfragen: Kontinuitäten und Diskontinuitäten der Landesplanung in Bayern

Als der Zweite Weltkrieg im Mai 1945 zu Ende ging, gab es keine "Stunde Null", auch in der bayerischen Landesplanung nicht, obwohl lange Zeit das Narrativ gepflegt wurde, ihre Geschichte beginne erst mit den organisatorisch-administrativen Neuregelungen nach dem Untergang des "Dritten Reichs". Weiter zurückreichende Wurzeln und Traditionen blieben damit ausgeklammert, die NS-Planungsgeschichte in Bayern brauchte man nicht zu thematisieren. In diesem Beitrag werden die Kontinuitäten ebenso kritisch betrachtet wie die Diskontinuitäten; die Zäsur des Jahres 1945 wird historisiert. Untersucht werden Rechtsgrundlagen und Personal der Landesplanung im Freistaat, danach folgt eine Skizze ihrer Aufgaben im Wandel der Zeit. Von besonderem Interesse ist dabei die Frage nach den Umständen, die in den 1960er-Jahren zu umfassenden und langfristig angelegten Plänen führten, zu denen es nur wenige Vorarbeiten gab. Dennoch zeigen sich bei genauerem Hinsehen auch hier deutliche Kontinuitätslinien etwa auf dem Feld der Energie- und Verkehrspolitik, die eine Brücke schlagen zwischen den späten 1930er-Jahren und der Planungseuphorie des ausgehenden "Wirtschaftswunders".When the Second World War came to an end in May 1945 there was no 'zero hour', not even in Bavarian state planning, despite the long-lived narrative that its history began with the reorganisation of the administration after the demise of the 'Third Reich'. Deeper roots and traditions were thus excluded and there was apparently no need to discuss National Socialist planning history in Bavaria. This article critically considers both continuities and discontinuities, the turning point of 1945 is historicised. The legal foundations and personnel of Bavarian state planning are investigated and their changing tasks outlined. Of particular interest are the conditions that in the 1960s led to the development of comprehensive and long-term plans for which there were few precursors. Nonetheless, a closer look reveals clear continuities even here, for instance in the field of energy and transport policy. These continuities create a link between the late 1930s and the planning euphoria at the end of the 'economic miracle'

Analyzing Longitudinal wb-MRI Data and Clinical Course in a Cohort of Former Smoldering Multiple Myeloma Patients: Connections between MRI Findings and Clinical Progression Patterns

The purpose of this study was to analyze size and growth dynamics of focal lesions (FL) as well as to quantify diffuse infiltration (DI) in untreated smoldering multiple myeloma (SMM) patients and correlate those MRI features with timepoint and cause of progression. We investigated 199 whole-body magnetic resonance imaging (wb-MRI) scans originating from longitudinal imaging of 60 SMM patients and 39 computed tomography (CT) scans for corresponding osteolytic lesions (OL) in 17 patients. All FLs >5 mm were manually segmented to quantify volume and growth dynamics, and DI was scored, rating four compartments separately in T1- and fat-saturated T2-weighted images. The majority of patients with at least two FLs showed substantial spatial heterogeneity in growth dynamics. The volume of the largest FL (p = 0.001, c-index 0.72), the speed of growth of the fastest growing FL (p = 0.003, c-index 0.75), the DI score (DIS, p = 0.014, c-index 0.67), and its dynamic over time (DIS dynamic, p < 0.001, c-index 0.67) all significantly correlated with the time to progression. Size and growth dynamics of FLs correlated significantly with presence/appearance of OL in CT within 2 years after the respective MRI assessment (p = 0.016 and p = 0.022). DIS correlated with decrease of hemoglobin (p < 0.001). In conclusion, size and growth dynamics of FLs correlate with prognosis and local bone destruction. Connections between MRI findings and progression patterns (fast growing FL—OL; DIS—hemoglobin decrease) might enable more precise diagnostic and therapeutic approaches for SMM patients in the future

Protocol of the IntenSify-Trial:An open-label phase I trial of the CYP3A inhibitor cobicistat and the cytostatics gemcitabine and nab-paclitaxel in patients with advanced stage or metastatic pancreatic ductal adenocarcinoma to evaluate the combination's pharmacokinetics, safety, and efficacy

Expression of CYP3A5 protein is a basal and acquired resistance mechanism of pancreatic ductal adenocarcinoma cells conferring protection against the CYP3A and CYP2C8 substrate paclitaxel through metabolic degradation. Inhibition of CYP3A isozymes restores the cells sensitivity to paclitaxel. The combination of gemcitabine and nab-paclitaxel is an established regimen for the treatment of metastasized or locally advanced inoperable pancreatic cancer. Cobicistat is a CYP3A inhibitor developed for the pharmacoenhancement of protease inhibitors. The addition of cobicistat to gemcitabine and nab-paclitaxel may increase the antitumor effect. We will conduct a phase I dose escalation trial with a classical 3 + 3 design to investigate the safety, tolerability, and pharmacokinetics (PKs) of gemcitabine, nab-paclitaxel, and cobicistat. Although the doses of gemcitabine (1000 mg/m2) and cobicistat (150 mg) are fixed, three dose levels of nab-paclitaxel (75, 100, and 125 mg/m2) will be explored to account for a potential PK drug interaction. After the dose escalation phase, we will set the recommended dose for expansion (RDE) and treat up to nine patients in an expansion part of the trial. The trial is registered under the following identifiers EudraCT-Nr. 2019-001439-29, drks.de: DRKS00029409, and ct.gov: NCT05494866. Overcoming resistance to paclitaxel by CYP3A5 inhibition may lead to an increased efficacy of the gemcitabine and nab-paclitaxel regimen. Safety, efficacy, PK, and RDE data need to be acquired before investigating this combination in a large-scale clinical study.</p

The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition

Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against Mycobacterium tuberculosis. To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent