Die neogene Entwicklung des zentralen Tien Schan, Kasachstan. Erste Ergebnisse von Apatit-Spaltspurdatierungen und morphotektonischer Analyse von Satellitendaten

Der Tien Schan ist ein etwa E–W erstrecktes, rund 2500km langes und bis 250km breites Gebirge in Zentralasien. Einzelne Gipfel sind über 7000m hoch. Obwohl durch die Kollision Indiens mit Asien entstanden, ist der Tien Schan ein Intraplatten-Orogen, dessen Hebung lange nach dem Beginn der Kollision vor 50Ma und weit nördlich der Sutur einsetzte (Sobel & Dumitru 1997). Von Tibet ist der Tien Schan durch das kaum deformierte Tarim-Becken getrennt. Hohe und schroffe Topographie, starke Seismizität (Molnar & Ghose 2000) und GPS-Daten zeigen, dass das Orogen auch heute sehr aktiv ist (Abdrakhmatov et al. 1996, Reigber et al. 2001). Der Tien Schan nimmt gegenwärtig etwa 40% der Gesamtkonvergenz Indiens mit Asien auf. Die Struktur des Tien Schan wird dominiert von E–Wstreichenden, nach N und S gerichteten Überschiebungen (Avouac et al. 1993, Yin et al. 1998), die sich meist deutlich in der Morphologie äußern. Auffallend ist die großräumige Gliederung des Orogens durch NW–SE-streichende dextrale Blattverschiebungen, die auch in das nördliche Vorland reichen (Tapponnier & Molnar 1979). Den Unterbau des Tien Schan bildet ein paläozoisches Akkretionsorogen (Zonenshajn et al. 1990). Im Mesozoikum entstand eine ausgedehnte Fastebene. In der späten Kreide oder dem frühen Tertiär setzte die Ablagerung kontinentaler Serien ein, die im jüngeren Känozoikum sehr mächtig werden. Die synorogenen Sedimente liegen manchmal konkordant, oft aber auch deutlich winkeldiskordant auf dem paläozoischen Sockel. In beiden Fällen bilden sie häufig asymmetrische Falten, die oft mit Störungen verknüpft sind. Geländestufen und ein starker Einfluss auf die Entwicklung des Entwässerungsnetzes weisen viele Störungen als gegenwärtig aktiv aus. Unser Untersuchungsgebiet liegt im Südosten Kasachstans. Es umfasst die Nordflanke des Tien Schan und seinen zentralen Teil mit den höchsten Erhebungen. Im Untersuchungsgebiet liegt das nach E propagierende Ende eines seismisch aktiven Störungssystems, das weiter westlich die nördliche Randstörung des Gebirges bildet, wo es unter der Millionenstadt Almaty (Alma- Ata) verläuft und eine ernste Bedrohung darstellt. Die Entwicklung dieses Störungssystems soll über verschiedene Zeitskalen mit verschiedenen Methoden untersucht werden...conferenc

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Why do family doctors prescribe potentially inappropriate medication to elderly patients?

Background Based on changes in pharmacokinetics and –dynamics in elderly patients, there are potentially inappropriate medications (PIM) that should be avoided in patients aged ≥ 65 years. Current studies showed prescription rates of PIM between 22.5 and 28.4 % in the primary care setting. The evidence concerning reasons for PIM prescription by FPs is limited. Methods This mixed method study consisted of three research parts: 1) semi-standardized content analysis of patients’ records, 2) qualitative interviews with FPs using a) open questions and b) selected patient-specific case vignettes and 3) qualitative interviews with FPs’ medical assistants. The integration of qualitative interviews was used to explain the quantitative results (triangulation design). PIM were identified according to the German PRISCUS list. Descriptive and multivariate statistical analysis was done using SPSS 22.0. Qualitative content analysis of interviews was used to classify the content of the interviews for indicating pertinent categories. All data were pseudonymously recorded and analyzed. Results Content analysis of 1846 patients’ records and interviews with 7 related FPs were conducted. Elderly patients [n = 1241, mean age: 76, females: 56.6 %] were characterized in average by 8.3 documented chronic diagnosis. 23.9 % of elderly patients received at least one PIM prescription. Sedatives/hypnotics were the most frequent prescribed PIM-drugs (13.7 %). Mental disorders, gender and number of long-term medication were detected as predictors for the probability of a PIM prescription. Common reported reasons for PIM prescription by FPs concerned limited knowledge regarding PIM, limited applicability of PIM lists in daily practice, lack of time, having no alternatives in medication, stronger patient-related factors than age that influence prescription, own bad experiences regarding changes of medication or refusal of following prescriptions of sedative/hypnotics. Conclusions It is essential to see FPs in a complex decision making situation with several influencing factors on their prescribing, including: patient-oriented prioritization, FPs’ experiences in daily practice, FPs’ knowledge regarding existing recommendations and their trust in it and organizational characteristics of FPs’ daily medical practice. These pros and cons of PIM prescription in elderly patients should be considered in FPs’ advanced training

Local Li cation coordination and dynamics in novel solid electrolytes

Abstract Research on solid ionic conductors for use as electrolytes in all solid state batteries still constitutes a rather vivid branch of today´s materials science. Despite enormous efforts, neither the development of a solid electrolyte fulfilling the key requirements such as mechanical stability and high ionic conductivity at ambient temperature has been successful nor has an extended understanding of the local Li coordination motifs in the often amorphous systems been obtained. In this contribution, recent progress both in the development of novel solid state electrolytes with high ionic conductivity and mechanical stability and in the characterization of the local Li coordination motifs in these electrolytes from our laboratory is presented. The work was performed as a project within the framework of the Collaborative Research Centre SFB 458 “Ionic Motion in Materials with Disordered Structures — From Elementary Steps to Macroscopic Transport”. Results will be given for polymer electrolytes based on polyethylene oxide (PEO), polyphosphazene (PPZ) and polyacrylonitrile (PAN) with various Li salts, nano-composites of these polymer electrolytes and Al2O3 as a ceramic filler, novel inorganic/organic hybrid electrolytes, in which a mixture of an ionic liquid and Li salt is confined within the pore system of a SiO2 glass, and a crystalline electrolyte, Li5La3Nb2O12. Employing a range of advanced solid state NMR methodologies including dipolar based NMR techniques and pulsed field gradient (PFG) NMR and impedance spectroscopy we were able to obtain a detailed knowledge about the local Li cation coordination motifs and the mechanism of Li transport in these electrolytes. Especially the hybrid electrolytes and the salt rich PAN based polymer electrolytes were identified as rather promising materials which combine a high ionic conductivity and mechanical stability.</jats:p

The catabolism of 3,3'-thiodipropionic acid in Variovorax paradoxus strain TBEA6: A proteomic analysis.

Variovorax paradoxus strain TBEA6 is one of the few organisms known to utilize 3,3'-thiodipropionate (TDP) as the only source of carbon and energy. It cleaves TDP to 3-mercaptopropionate (3MP), which is a direct precursor for polythioester synthesis. To establish this process in V. paradoxus TBEA6, it is crucial to unravel its TDP metabolism. Therefore, a proteomic approach with subsequent deletion of interesting genes in the bacterium was chosen. Cells were cultivated with D-gluconate, TDP or 3-sulfinopropionate as the only carbon sources. Proteins with high abundances in gels of cells cultivated with either of the organic sulfur compounds were analyzed further. Thereby, we did not only confirm parts of the already postulated TDP metabolism, but also eight new protein candidates for TDP degradation were detected. Deletions of the corresponding genes (two enoyl-CoA hydratases (Ech-20 and Ech-30), an FK506-binding protein, a putative acetolactate synthase, a carnitinyl-CoA dehydratase, and a putative crotonase family protein) were obtained. Only the deletions of both Ech-20 and Ech-30 led to a TDP negative phenotype. The deletion mutant of VPARA_05510, which encodes the putative crotonase family protein showed reduced growth with TDP. The three genes are located in one cluster with genes proven to be involved in TDP metabolism. Thermal shift assays showed an increased stability of Ech-20 with TDP-CoA but not with TDP. These results indicate that Ech-20 uses TDP-CoA as a substrate instead of TDP. Hence, we postulate a new putative pathway for TDP metabolism. Ech-30 interacts with neither TDP-CoA nor TDP but might interact with other CoA-activated intermediates of the proposed pathway. Further enzyme characterization is necessary to unravel the complete pathway from TDP to 3MP