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Andresen, Gorm Bruun ; Rasmussen, Morten Grud ; Rodriguez, Rolando A. ; Becker, Sarah ; Greiner, Martin
We introduce a top-down stylized model to analyse the impact of a transition to a European power system based only on wind and solar power. Wind and solar power generation is calculated from high-resolution weather data and based on the country specific electricity demand alone, we introduce a model of the conventional power system that facilitates simple spatio-temporal modelling of its macroscopic behavior without direct reference to the underlying technological, economical, and political development in the system. Using this model, we find that wind and solar power generation can replace conventional power generation and power capacity to a large degree if power transmission across the continent is made possible.
Die Erfahrung ist wohl jedem bekannt, der schreibt und liest, daß ein Satz dann verstanden ist, wenn man das, was er besagt, auch anders formulieren könne. Andererseits gibt es eine eigentümliche Resistenz auch verstandener Worte, ihren Gehalt einfach in neue Formen umzugießen - es gibt zumal im poetischen Text eine Verschmelzung von Evidenz und Einzigkeit, und zwar auch für den Verfasser eines solchen Textes. Nicht ohne Grund scheidet man die "intentio auctoris" von der "intentio operis", gerade am eigenen Text ist dieses Sich-Entziehen des Wortes vielleicht sogar am drastischsten und geradezu bestürzendsten zu sehen.
Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder
(2021)
Konrad, Kerstin ; Kohls, Gregor ; Baumann, Sarah ; Bernhard, Anka ; Martinelli, Anne ; Ackermann, Katharina ; Smaragdi, Areti ; Gonzalez-Madruga, Karen ; Wells, Amy ; Rogers, Jack C. ; Pauli, Ruth ; Clanton, Roberta ; Baker, Rosalind ; Kersten, Linda ; Prätzlich, Martin ; Oldenhof, Helena ; Jansen, Lucres ; Kleeven, Anneke ; Bigorra, Aitana ; Hervás, Amaia ; Kerexeta-Lizeaga, Iñaki ; Sesma-Pardo, Eva ; Gonzalez-Torres, Miguel Angel ; Siklósi, Réka ; Dochnal, Roberta ; Kalogerakis, Zacharias ; Pirlympou, Mara ; Papadakos, Leonidas ; Cornwell, Harriet ; Scharke, Wolfgang ; Dikeos, Dimitris ; Fernández-Rivas, Aranzazu ; Popma, Arne ; Stadler, Christina ; Herpertz-Dahlmann, Beate ; De Brito, Stephane A. ; Fairchild, Graeme ; Freitag, Christine M.
Background: Conduct disorder (CD) rarely occurs alone but is typically accompanied by comorbid psychiatric disorders, which complicates the clinical presentation and treatment of affected youths. The aim of this study was to investigate sex differences in comorbidity pattern in CD and to systematically explore the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses of female CD.
Methods: As part of the FemNAT-CD multisite study, semistructured clinical interviews and rating scales were used to perform a comprehensive phenotypic characterization of 454 girls and 295 boys with CD (9–18 years), compared to 864 sex- and age-matched typically developing controls.
Results: Girls with CD exhibited higher rates of current major depression, anxiety disorders, post-traumatic stress disorder and borderline personality disorder, whereas boys with CD had higher rates of current attention-deficit/hyperactivity disorder. In line with the ‘gender paradox’ hypothesis, relative to boys, girls with CD showed significantly more lifetime psychiatric comorbidities (incl. Alcohol Use Disorder), which were accompanied by more severe CD symptoms. Female and male youths with CD also differed significantly in their CD symptom profiles and distribution of age-of-onset subtypes of CD (i.e. fewer girls with childhood-onset CD). In line with the ‘delayed-onset pathway’ hypothesis, girls with adolescent-onset CD showed similar levels of dimensional psychopathology like boys with childhood-onset CD, while boys with adolescent-onset CD had the lowest levels of internalizing psychopathology.
Conclusions: Within the largest study of CD in girls performed to date, we found compelling evidence for sex differences in comorbidity patterns and clinical presentation of CD. Our findings further support aspects of the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses by showing that girls with CD had higher rates of comorbid lifetime mental disorders and functional impairments, and they usually developed CD during adolescence. These novel data on sex-specific clinical profiles of CD will be critical in informing intervention and prevention programmes.
Molecular surveillance of carbapenem-resistant gram-negative bacteria in liver transplant candidates
(2021)
Schultze, Tilman ; Ferstl, Philip ; Villinger, David ; Hogardt, Michael ; Bechstein, Wolf Otto ; Göttig, Stephan ; Wichelhaus, Thomas Alexander ; Zeuzem, Stefan ; Trebicka, Jonel ; Waidmann, Oliver ; Welker, Martin-Walter ; Kempf, Volkhard A. J.
Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes.
Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts.
Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN.
Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
Bahls, Martin ; Lorenz, Matthias W. ; Dörr, Marcus ; Gao, Lu ; Kitagawa, Kazuo ; Tuomainen, Tomi-Pekka ; Agewall, Stefan ; Berenson, Gerald ; Catapano, Alberico L. ; Norata, Giuseppe D. ; Bots, Michiel L. ; Gilst, Wiek van ; Asselbergs, Folkert W. ; Brouwers, Frank P. ; Uthoff, Heiko ; Sander, Dirk ; Poppert, Holger ; Hecht Olsen, Michael ; Empana, Jean Philippe ; Schminke, Ulf ; Baldassarre, Damiano ; Veglia, Fabrizio ; Franco, Oscar H. ; Kavousi, Maryam ; Groot, Eric de ; Mathiesen, Ellisiv B. ; Grigore, Liliana ; Polak, Joseph F. ; Rundek, Tatjana ; Stehouwer, Coen D. A. ; Skilton, Michael R. ; Hatzitolios, Apostolos I. ; Savopoulos, Christos ; Ntaios, George ; Plichart, Matthieu ; McLachlan, Stela ; Lind, Lars ; Willeit, Peter ; Steinmetz, Helmuth ; Desvarieux, Moise ; Ikram, M. Arfan ; Johnsen, Stein Harald ; Schmidt, Caroline ; Willeit, Johann ; Ducimetiere, Pierre ; Price, Jackie F. ; Bergström, Göran ; Kauhanen, Jussi ; Kiechl, Stefan ; Sitzer, Matthias ; Bickel, Horst ; Sacco, Ralph L. ; Hofman, Albert ; Völzke, Henry ; Thompson, Simon G.
Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.
Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.
Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.
Atar, Leyla ; Paschalis, Stefanos ; Barbieri, Carlo ; Bertulani, Carlos A. ; Díaz Fernández, Paloma ; Holl, Matthias ; Najafi, Mohammad Ali ; Panin, Valerii ; Alvarez-Pol, Héctor ; Aumann, Thomas ; Avdeichikov, Vladimir ; Beceiro-Novo, Saul ; Bemmerer, Daniel ; Benlliure Anaya, Jose Fernando ; Boillos Betete, Juan Manuel ; Boretzky, Konstanze ; Garcia Borge, Maria José ; Caamaño, Manuel ; Caesar, Christoph ; Casarejos Ruiz, Enrique ; Catford, Wilton N. ; Cederkäll, Joakim ; Chartier, Marielle ; Chulkov, Leonid V. ; Cortina Gil, Dolores ; Cravo, Edgar ; Crespo, Raquel ; Dillmann, Iris ; Elekes, Zoltán ; Enders, Joachim ; Ershova, Olga ; Estradé Vaz, Alfredo ; Farinon, Fabio ; Fraile Prieto, Luis Mario ; Freer, Martin ; Galaviz Redondo, Daniel ; Geissel, Hans ; Gernhäuser, Roman ; Golubev, Pavel ; Göbel, Kathrin ; Hagdahl, Julius ; Heftrich, Tanja ; Heil, Michael ; Heine, Marcel ; Heinz, Andreas ; Henriques, Ana ; Hufnagel, Alexander ; Ignatov, Alexander ; Johansson, Håkan T. ; Jonson, Björn ; Kahlbow, Julian ; Kalantar-Nayestanaki, Nasser ; Kanungo, Rituparna ; Kelic-Heil, Aleksandra ; Knyazev, Alexander ; Kröll, Thorsten ; Kurz, Nikolaus ; Labiche, Marc ; Langer, Christoph ; Le Bleis, Tudi ; Lemmon, Roy Crawford ; Lindberg, Simon ; Machado, Jorge ; Marganiec-Gałązka, J. ; Movsesyan, Alina ; Nácher González, Enrique ; Nikolskii, Evgenii Y. ; Nilsson, Thomas ; Nociforo, Chiara ; Perea Martinez, Angel ; Petri, Marina ; Pietri, Stephane ; Plag, Ralf ; Reifarth, René ; Ribeiro Jimenez, Guillermo ; Rigollet, Catherine ; Rossi, Dominic M. ; Röder, Marko ; Savran, Deniz ; Scheit, Heiko ; Simon, Haik ; Sorlin, Olivier ; Syndikus, Ina ; Taylor, Jonathan Thomas ; Tengblad, Olof ; Thies, Ronja ; Togano, Yasuhiro ; Vandebrouck, Marine ; Velho, Paulo ; Volkov, Vasily ; Wagner, Andreas ; Wamers, Felix ; Weick, Helmut ; Wheldon, Carl ; Wilson, Gemma Louise ; Winfield, John S. ; Woods, Philip John ; Yakorev, Dmitry ; Zhukov, Mikhail V. ; Zilges, Andreas ; Zuber, Kai
Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R3B/LAND setup with incident beam energies in the range of 300–450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type AO(p,2p)A−1N have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.
Saafan, Hisham ; Alahdab, Ahmad ; Michelet, Robin ; Gohlke, Linus ; Ziemann, Janine ; Holdenrieder, Stefan ; McLaughlin, Katie-May ; Wass, Mark N. ; Cinatl, Jindrich ; Michaelis, Martin ; Kloft, Charlotte ; Ritter, Christoph A .
Exploring mechanisms of drug resistance to targeted small molecule drugs is critical for an extended clinical benefit in the treatment of non-small cell lung cancer (NSCLC) patients carrying activating epidermal growth factor receptor (EGFR) mutations. Here, we identified constitutive cell proliferation regulating inhibitor of protein phosphatase 2A (CIP2A) in the HCC4006rErlo0.5 NSCLC cell line adapted to erlotinib as a model of acquired drug resistance. Constitutive CIP2A resulted in a constitutive activation of Akt signaling. The proteasome inhibitor bortezomib was able to reduce CIP2A levels, which resulted in an activation of protein phosphatase 2A and deactivation of Akt. Combination experiments with erlotinib and bortezomib revealed a lack of interaction between the two drugs. However, the effect size of bortezomib was higher in HCC4006rErlo0.5, compared to the erlotinib-sensitive HCC4006 cells, as indicated by an increase in Emax (0.911 (95%CI 0.867–0.954) vs. 0.585 (95%CI 0.568–0.622), respectively) and decrease in EC50 (52.4 µM (95%CI 46.1–58.8 µM) vs. 73.0 µM (95%CI 60.4–111 µM), respectively) in the concentration–effect model, an earlier onset of cell death induction, and a reduced colony surviving fraction (0.38 ± 0.18 vs. 0.95 ± 0.25, respectively, n = 3, p < 0.05). Therefore, modulation of CIP2A with bortezomib could be an interesting approach to overcome drug resistance to erlotinib treatment in NSCLC.