survey among thesis supervisors at a large German university hospital

Objectives: To identify underlying causes for failure of medical thesis projects and the constantly high drop-out rate in Germany from the supervisors' perspective and to compare the results with the students' perspective. Setting: Cross-sectional survey. Online questionnaire for survey of medical thesis supervisors among the staff of Charité—Universitätsmedizin Berlin, Germany. Published, earlier longitudinal survey among students for comparison. Participants: 1069 thesis supervisors participated. Data extraction and synthesis: Data are presented using descriptive statistics, and the χ2 test served to compare the results among supervisors with the earlier data from the longitudinal survey of doctoral students. Primary and secondary outcomes: Not applicable. This survey is an observational study. Results: Of 3653 potential participants, 1069 (29.3%) supervising 3744 doctoral candidates participated in the study. Supervisors considered themselves to be highly motivated and to offer adequate supervision. On the other hand, 87% stated that they did not feel well prepared for thesis supervision. Supervisors gave lack of timeliness of doctoral students and personal differences (p=0.024 and p=0.001) as the main reasons for terminating thesis projects. Doctoral students predominantly mentioned methodological problems and difficult subjects as critical issues (p=0.001 and p<0.001). Specifically, students felt ill prepared for the statistical part of their research—49.5% stated that they never received statistical assistance, whereas 97% of supervisors claimed to help their students with statistical analysis. Conclusions: The authors found that both thesis supervisors and medical students feel ill prepared for their roles in the process of a medical dissertation. Contradictory reasons for terminating medical thesis projects based on supervisors' and students' self- assessment suggest a lack of communication and true scientific collaboration between supervisors and doctoral students as the major underlying issue that requires resolution

Sensitivity of Bunker Cave to climatic forcings highlighted through multi-annual monitoring of rain-, soil-, and dripwaters

The last two decades have seen a considerable increase in studies using speleothems as archives of past climate variability. Caves under study are now monitored for a wide range of environmental parameters and results placed in context with speleothem data. The present study investigates trends from a seven year long monitoring of Bunker Cave, northwestern Germany, in order to assess the hydraulic response and transfer time of meteoric water from the surface to the cave. Rain-, soil-, and dripwater were collected from August 2006 to August 2013 at a monthly to bimonthly resolution and their oxygen and hydrogen isotope composition was measured. Furthermore, drip rates were quantified. Due to different drip characteristics, annual mean values were calculated for the drip rates of each drip site. Correlations of the annual mean drip rate of each site with precipitation and infiltration demonstrate that the annual infiltration, and thus the annual precipitation control the inter-annual drip-rate variability for all except one site. The hydraulic response is not delayed on an annual basis. All drip sites display identical long-term trends, which suggests a draining of a common karst reservoir over these seven years of monitoring. Correlations of soil- and dripwater monthly δ18O and δD values with atmospheric temperature data reveal water transfer times of 3 months to reach a depth of 40 cm (soilwater at site BW 2) and 4 months for 70 cm depth (soilwater at site BW 1). Finally, the water reaches the cave chambers (15 to 30 m below land surface) after ca. 2.5 years. Consequently, a temporal offset of 29 to 31 months (ca. 2.5 years) between the hydraulic response time (no time lag on annual basis) and the water transfer time (time lag of 29 to 31 months) was found, which is negligible with regard to Bunker Cave speleothems because of their slow growth rates. Here, proxies recording precipitation/infiltration and temperature are registered on a decadal scale. Variations in drip rate and thus precipitation and infiltration are recorded by δ13C and Mg/Ca ratios in speleothem calcite. Speleothem δ18O values reflect both temperature and precipitation signals due to drip rate-related fractionation processes. We document that long-term patterns in temperature and precipitation are recorded in dripwater patterns of Bunker Cave and that these are linked to the North Atlantic Oscillation (NAO)

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development

12 pags., 4 figs., 3 tabs.SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome.Work at BMRZ is supported by the state of Hesse. Work in Covid19-NMR was supported by the Goethe Corona Funds, by the IWBEFRE-program 20007375 of state of Hesse, the DFG through CRC902: “Molecular Principles of RNA-based regulation.” and through infrastructure funds (project numbers: 277478796, 277479031, 392682309, 452632086, 70653611) and by European Union’s Horizon 2020 research and innovation program iNEXT-discovery under grant agreement No 871037. BY-COVID receives funding from the European Union’s Horizon Europe Research and Innovation Programme under grant agreement number 101046203. “INSPIRED” (MIS 5002550) project, implemented under the Action “Reinforcement of the Research and Innovation Infrastructure,” funded by the Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and co-financed by Greece and the EU (European Regional Development Fund) and the FP7 REGPOT CT-2011-285950—“SEE-DRUG” project (purchase of UPAT’s 700 MHz NMR equipment). The support of the CERM/CIRMMP center of Instruct-ERIC is gratefully acknowledged. This work has been funded in part by a grant of the Italian Ministry of University and Research (FISR2020IP_02112, ID-COVID) and by Fondazione CR Firenze. A.S. is supported by the Deutsche Forschungsgemeinschaft [SFB902/B16, SCHL2062/2-1] and the Johanna Quandt Young Academy at Goethe [2019/AS01]. M.H. and C.F. thank SFB902 and the Stiftung Polytechnische Gesellschaft for the Scholarship. L.L. work was supported by the French National Research Agency (ANR, NMR-SCoV2-ORF8), the Fondation de la Recherche Médicale (FRM, NMR-SCoV2-ORF8), FINOVI and the IR-RMN-THC Fr3050 CNRS. Work at UConn Health was supported by grants from the US National Institutes of Health (R01 GM135592 to B.H., P41 GM111135 and R01 GM123249 to J.C.H.) and the US National Science Foundation (DBI 2030601 to J.C.H.). Latvian Council of Science Grant No. VPP-COVID-2020/1-0014. National Science Foundation EAGER MCB-2031269. This work was supported by the grant Krebsliga KFS-4903-08-2019 and SNF-311030_192646 to J.O. P.G. (ITMP) The EOSC Future project is co-funded by the European Union Horizon Programme call INFRAEOSC-03-2020—Grant Agreement Number 101017536. Open Access funding enabled and organized by Projekt DEALPeer reviewe

Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form

Late Pleistocene cryogenic calcite spherolites from the Malachitdom Cave (NE Rhenish Slate Mountains, Germany): origin, unusual internal structure and stable C-O isotope composition

Cryogenic calcites yielded U-series ages in the range from 15.61±0.20 ka to 14.48±0.12 ka, which is the youngest age obtained so far for this type of cryogenic cave carbonates in Europe. Most of these particles of the Malachitdom Cave (NE Brilon, Sauerland, North Rhine-Westphalia) are complex spherolites usually smaller than 1 cm. They show δ13C-values between –1 and –5 ‰ VPDB and δ18O-values ranging from –7 to –16 ‰ VPDB, the δ13C-values increase and the δ18O-values decrease from centre to border. The complex spherolites are interpreted to be formed in slowly freezing pools of residual water on ice, a situation that repeatedly occurred during the change of glacial to interglacial periods in the periglacial areas of Central Europe. After the melting of the caveice, the complex spherolites make up one type of cryogenic calcite particles in the arenitic to ruditic sediment

Particle-based production of antibiotic rebeccamycin with Lechevalieria aerocolonigenes

Rebeccamycin is a promising antibiotic synthesized by the filamentous bacterium Lechevalieria aerocolonigenes. To date, the main investigations were focused on the biological effect or the structure elucidation of rebeccamycin. The aim of this study was to develop an efficient cultivation process based on shake flask experiments. The relationship between morphology and productivity and the positive effects of micro- and macroparticle enhanced cultivation on rebeccamycin production with this strain in the pellet-like morphology was investigated. The addition of talc microparticles increased the rebeccamycin concentration to 120\ua0mg\ua0L and 3-fold compared to the control without microparticles. An up to 9-fold increase in rebeccamycin concentration was achieved using surface modified talc particles. Through the addition of glass beads as macroparticles, the highest rebeccamycin concentration of approximately 120\ua0mg\ua0L was achieved by the induction of mechanical stress. Cultivation with glass beads enhanced the rebeccamycin concentration 22-fold compared to the control without macroparticles. By further increasing the diameter of the glass beads and increasing mechanical stress, the morphology was driven toward mycelial growth and the productivity was decreased. An adjusted mechanical stress, through the addition of macro-shaped glass bead particles, led to the desired increase in productivity

Health and health risk behaviour of adolescents—Differences according to family structure. Results of the German KiGGS cohort study

<div><p>Objective</p><p>This study’s aim was to investigate the association between family structure and different health-related outcomes in adolescence (self-rated health, emotional and behavioural problems, health-related quality of life, regular smoking, and heavy episodic drinking). Furthermore, we analysed the extent to which socio-economic status, family cohesion and the pre-transition health status explain family structure-related health disparities.</p><p>Methods</p><p>We used longitudinal data from the first two waves of the German KiGGS cohort study carried out by the Robert Koch Institute (baseline: 2003–2006, follow-up: 2009–2012). The sample comprised 4,692 respondents aged 11 to 17 years. Using data from both waves, effects of family structure on health status at follow-up were calculated applying linear and logistic regression models.</p><p>Results</p><p>We found that adolescents continuously living with both birth parents were in good health. Adolescents whose parents separated after the baseline survey, reported poorer health and were more likely to smoke. The transition from stepfamily to single parent family was also associated with a higher risk of regular smoking. Lower health-related quality of life as well as higher scores for emotional and behavioural problems occurred in almost all non-nuclear family structures, although not all effects were statistically significant. No significant effects of family structure on heavy episodic drinking were found. While family cohesion mediated the effects of family structure on adolescents’ health, the mediating effect of socio-economic status was small. After controlling for pre-transition health, the effects were even lower.</p><p>Conclusions</p><p>Because the direct effects of family structure on adolescents’ health were small and family cohesion was found to be an important mediator in the association between family structure and adolescents’ health, prevention programmes and interventions should be directed towards the parent–adolescent relationship rather than just the family structure, in order to minimize the psychosocial stress of adolescents during the period of family transition.</p></div