Gotowa bibliografia na temat „Cologne (Germany). S. Andreastift”

Background: Although there have been no reported cardiac arrests in space to date, the risk of severe medical events occurring during long-duration spaceflights is a major concern. These critical events can endanger both the crew as well as the mission and include cardiac arrest, which would require cardiopulmonary resuscitation (CPR). Thus far, five methods to perform CPR in microgravity have been proposed. However, each method seems insufficient to some extent and not applicable at all locations in a spacecraft. The aim of the present study is to describe and gather data for two new CPR methods in microgravity. Materials and Methods: A randomized, controlled trial (RCT) compared two new methods for CPR in a free-floating underwater setting. Paramedics performed chest compressions on a manikin (Ambu Man, Ambu, Germany) using two new methods for a free-floating position in a parallel-group design. The first method (Schmitz–Hinkelbein method) is similar to conventional CPR on earth, with the patient in a supine position lying on the operator’s knees for stabilization. The second method (Cologne method) is similar to the first, but chest compressions are conducted with one elbow while the other hand stabilizes the head. The main outcome parameters included the total number of chest compressions (n) during 1 min of CPR (compression rate), the rate of correct chest compressions (%), and no-flow time (s). The study was registered on clinicaltrials.gov (NCT04354883). Results: Fifteen volunteers (age 31.0 ± 8.8 years, height 180.3 ± 7.5 cm, and weight 84.1 ± 13.2 kg) participated in this study. Compared to the Cologne method, the Schmitz–Hinkelbein method showed superiority in compression rates (100.5 ± 14.4 compressions/min), correct compression depth (65 ± 23%), and overall high rates of correct thoracic release after compression (66% high, 20% moderate, and 13% low). The Cologne method showed correct depth rates (28 ± 27%) but was associated with a lower mean compression rate (73.9 ± 25.5/min) and with lower rates of correct thoracic release (20% high, 7% moderate, and 73% low). Conclusions: Both methods are feasible without any equipment and could enable immediate CPR during cardiac arrest in microgravity, even in a single-helper scenario. The Schmitz–Hinkelbein method appears superior and could allow the delivery of high-quality CPR immediately after cardiac arrest with sufficient quality.

Abstract Background Due to severe immunosuppression, patients undergoing allogeneic hematopoietic stem cell transplantation (aSCT) are at increased risk of infection and especially bloodstream infections (BSI) remain a major cause of death. Knowledge of the specific epidemiology of pathogens and resistances is of utmost importance to optimize antimicrobial treatment strategies. Methods Based on the Cologne Cohort of Neutropenic Patients (CoCoNut) database, we conducted a retrospective analysis of blood cultures collected within 100 days following transplantation of patients undergoing aSCT between January 2009 and December 2018 at the University Hospital of Cologne, Germany. Contamination of coagulase-negative Staphylococci (CoNS) isolates (single positive isolate within 5 days) was considered within the analysis. Results In total, 843 aSCT patients were available for analysis (484/843 [57%] male). The median age was 53 (interquartile range [IQR] 43–62) years, predominant underlying diseases were acute myeloid leukemia (47%, 397/843), lymphoma (14%, 117/843), and acute lymphoblastic leukemia (11%, 89/843). Median inpatient stay was 39 (IQR 34–50) days, while 67/843 (8%) patients died. Antibacterial prophylaxis was administered in 289/843 (34%) and antifungal prophylaxis in 738/843 (88%) patients. BSI was diagnosed in 233/843 (28%) patients. In total, 5,489 pairs of blood cultures were taken (median 4 per patient, IQR 2–8), while a pathogen could only be detected in 922/5,489 (17%). Most frequent pathogens were CoNS (259/922, 28%), Enterococcus spp. (219/922, 24%), E. coli (132/922, 14%), Klebsiella spp. (44/922, 5%), P. aeruginosa (39/922, 4%), S. aureus (37/922, 4%), and Candida spp. (42/922, 5%). Polymicrobial infection was detected in 58/922 (6%) cases. Within Enterococci isolates, 24/219 (11%) were VRE. None of the Klebsiella, but 9/132 (7%) of E. coli isolates were ESBL positive. In 4/37 (11%) cases S. aureus isolates were MRSA. Conclusion Patients in the early phase after aSCT are at high risk of BSI with a predominantly gram-positive spectrum. Empirical antimicrobial treatment must consider pathogen epidemiology and resistance patterns while waiting for blood culture results. Disclosures All authors: No reported disclosures.

It is not surprising that Henry Edward Manning had strong opinions about the Kulturkampf, Otto von Bismarcks effort in the early 1870’s to bring the Roman Catholic Church in Germany under the control of the State. As head of the Catholic Church in England, it appropriately fell to Manning to condemn what most British Catholics would have seen as the persecution of their Church in the new German Empire. Moreover, Manning knew personally the bishops involved in the conflict with Bismarck from their time together at the Vatican Council. Indeed, he was well acquainted with some of them who had played important rôles, either for or against, in the great controversies of the Council that led to the definition of Papal Infallibility. MiecisIaus Ledochowski, Archbishop of Gnesen and Posen, imprisoned and expelled from his see by the German government in 1874, had, together with Manning, been a prominent infallibilist. Paulus Melchers, Archbishop of Cologne, and leader of the German inopportunists, suffered the same penalty. The bishops of Breslau, Trier and Paderborn, all of whom had played significant rôles at the Council, the first two against, the latter for the definition, were either imprisoned, expelled, or both. Manning considered these men to have suffered for the cause of religious liberty, and could not understand the indifference of British politicians, especially of liberals like Gladstone, to their fate.

This paper outlines a research project which is being conducted in the edu¬cational context of an international Master program: In 2001, an interdisci¬plinary and cohort-based Master program entitled “International Manage¬ment and Intercultural Communication/GlobalMBA” was founded, which is currently offered by a four-university consortium that includes the follow¬ing: Technische Hochschule Köln (TH Köln), Cologne, Germany, the Fac¬ulty of Management at the University of Warsaw (UW), Poland, Dongbei University of Finance and Economics (DUFE) in Dalian, China, and the Coggin College of Business at the University of North Florida (UNF) in Jacksonville, USA. During the program´s 15-month duration, a multina¬tional cohort of 25-30 students recruited from each of the four universi¬ties studies together for one semester at each university. Much of the coursework and assignments as well as the final Master thesis are written in multinational groups of three to four students, thus requiring the students to permanently prove their teamwork skills. Besides, given the in-built mobility and multinational cohort-based structure of the program, the students are continuously exposed to a variety of different cultural experi¬ences and encounters. The program´s curriculum includes management-oriented courses as well as courses on the theory and practice of intercul¬tural communication. In one of these latter modules called Applied Inter¬cultural Communication, which is taught in every location and has a strong country-specific perspective, students are required to produce reflective dia¬ries describing their cultural experiences. The research project presented here started in 2013 and is based on a qualitative analysis of students´ diary entries written during a time span of 15 months as part of the course requirements for this particular module. The project is intended to serve two main purposes:

Abstract We previously identified the cause of low levels of von Willebrand factor (VWF) in the RIIIS/J mouse strain to be a regulatory mutation, Mvwf1, in an N-acetylgalactosaminyltransferase, B4galnt2 (previously designated Galgt2). Mvwf1 causes a tissue-specific switch in B4galnt2 expression from intestinal epithelium to vascular endothelium, resulting in aberrant glycosylation of VWF and accelerated clearance from circulation. We have identified thirteen Mvwf1 inbred mouse strains that share this remarkable tissue-specific switch and a common 97kb haplotype block, including a 30kb region of 2–3% sequence divergence that flanks Exon 1. An RIIIS/J BAC transgene containing the entire Mvwf1 haplotype block and B4galnt2 gene confers vascular gene expression, while C57BL6/J BAC transgenes spanning the homologous region confer “wild-type” vessel(−), intestine(+) gene expression, indicating that one or more tissue-specific regulatory elements sufficient to recapitulate the Mvwf1 tissue-specific switch lie within the genomic region covered by these BACs. A wild-derived recombinant Mvwf1 allele containing the 3′ half of the Mvwf1 haplotype block confers the vessel(−), intestine(+) B4galnt2 expression pattern, placing the regulatory mutation(s) responsible for the Mvwf1 switch well upstream of the proximal promoter region. Sequence analysis of DNA from wild-caught individual mice confirmed the presence of a highly conserved wild mouse Mvwf1 founder allele that likely pre-dates the development of the inbred mouse strains. PCR of genomic DNA from wild caught mice representing M. m. musculus, M. m. domesticus, M. m. castaneus, M. m. molossinus, M. spretus, M. hortulanis, and M. macedonicus revealed that the Mvwf1 allele is common in wild M. m. domesticus populations in North America, Europe, and Africa, with an allele frequency as high as 60% in French mice. Population samples of M. m. domesticus from Cologne, Germany and the Massif Central region of France drastically differ in the frequency of this allele (0% vs. 60%). A significant reduction in microsatellite variability at B4galnt2 in the French population, as measured by the lnRH statistic, suggests a recent, local shift in the frequency of Mvwf1, likely due to a recent change in selective pressure. Analysis of independently trapped wild mice from the Massif Central region of France confirmed that Mvwf1 confers vascular endothelial B4galnt2 expression and causes significantly lower VWF levels (5.5+2.0 vs. 13.3+2.3, p<1x10−7) in this population. These data support a B4Galnt2 allele-specific survival advantage in wild mice, leading us to speculate that a similar survival advantage could account for the high prevalence of VWD in human populations.

Abstract Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA) Background: There is accumulating evidence that the RANK/RANKL signaling pathway plays a pivotal role in breast tumorigenesis, particularly in the development of BRCA1-mutated tumors. Targeting the RANK pathway has been shown to attenuate breast cancer (BC) proliferation in vitro and in vivo. Studies using bone modifying agents as adjuvant therapy showed reduced rates of bone metastases and improved BC survival, as well as prevention of treatment-induced skeletal events. The GeparX clinical trial assessed the use of denosumab in patients with primary BC as an adjunct to neoadjuvant chemotherapy for its ability to enhance pathological complete response (pCR) rate and improve outcome. The trial randomized 780 patients twice to a total of 4 treatment groups (to receive or not receive denosumab; to receive nab-paclitaxel 125 mg/m2 weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles, both followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m2 every 2 weeks/every 3 weeks according to the investigator´s choice). Carboplatin was given in triple-negative breast cancer (TNBC), and trastuzumab biosimilar ABP980 plus pertuzumab was given in human epidermal growth factor-2-positive (HER2+) BC. Overall, the pCR (ypT0 ypN0) rate was 41% with denosumab vs 43% without; nab-paclitaxel at a dosage of 125 mg/m2 weekly resulted in a significantly higher pCR rate of 45% vs 39% with a dosage of 125 mg/m2 days 1 and 8 every 3 weeks. Research question: Does the germline mutation status of BRCA1/2 and other BC predisposition genes affect treatment outcome in the GeparX study? Methods: Genetic germline analyses assessing pathogenic variants in BRCA1/2 and 16 other BC predisposition genes were performed at the Center for Familial Breast and Ovarian Cancer, Cologne, Germany; 767 patients were included in this secondary investigation (308 TNBC, 306 HER2-/hormone receptor positive [HR+], 153 HER2+). Findings: Germline BRCA1/2 mutations were present in 91/767 patients (11.9%), with a higher mutation prevalence in TNBC (50/308, 16.2%) and HER2-/HR+ BC (37/306, 12.1%), and a low mutation prevalence in HER2+ BC (4/153, 2.6%). Overall, the pCR rate (ypT0 ypN0) was elevated in BRCA1/2 mutation carriers vs non-carriers (49.5% vs 41.1%, respectively; overall: OR 1.40, 95% CI 0.90-2.17; TNBC: OR 1.24, 95% CI 0.67-2.32; HER2-/HR+: OR 1.83, 95% CI 0.86-3.88). Highest pCR rates were observed in TNBC in BRCA1/2 mutation carriers vs non-carriers (60% vs. 54.7%, respectively). Highest pCR rate differences were observed HER2-/HR+ BC in BRCA1/2 mutation carriers vs non-carriers (32.4% vs. 20.8%, respectively). Regarding treatment arms, both BRCA1/2 mutation carriers and non-carriers benefitted most from nab-paclitaxel at a dosage of 125 mg/m2 weekly vs 125 mg/m2 days 1 and 8 every 3 weeks (BRCA1/2 mutation carriers: 55.3% vs 43.2%, respectively; OR 1.63, 95% CI 0.71-3.73; non-carriers: 43.7% vs 38.6%, respectively; OR 1.24, 95% CI 0.91-1.68). No beneficial effect was observed for denosumab vs no denosumab (51.1% vs 47.8% for BRCA1/2 mutation carriers, respectively; OR 1.14, 95% CI 0.50-2.60; 40.3% vs 41.9% for non-carriers, respectively; OR 0.94, 95% CI 0.69-1.27). Of the 617 BRCA1/2-negative patients, 59 patients carried mutations in other BC predisposition genes which did not predict therapy response compared to patients without any mutation. Conclusions: Irrespective of the treatment arm, higher pCR rates were observed in BRCA1/2 mutations carriers vs non-carriers. Both BRCA1/2 mutation carriers and non-carriers benefitted most from weekly nab-paclitaxel. No pronounced effect was observed for denosumab in either group. Key words: GeparX, denosumab, BRCA1/2 germline mutations, therapy response Funding: GeparX was financially supported by Amgen and BMS (Celgene). Citation Format: Rita K. Schmutzler, Theresa Link, Eric Hahnen, Mattea Reinisch, Jan Hauke, Marianne Just, Michael Untch, Corinna Ernst, Oliver Stötzer, Peter A. Fasching, Mohamad Kayali, Pauline Wimberger, Andreas Schneeweiss, Sandra Schmidt, Sabine Seiler, Christian Jackisch, Marc Thill, Kerstin Rhiem, Carsten Denkert, Valentina Nekljudova, Johannes Holtschmidt, Jens-Uwe Blohmer, Sibylle Loibl. Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-13.

Background/AimsTo analyse graft detachments prior to rebubbling, the influence of rebubbling on the postoperative outcome after Descemet membrane endothelial keratoplasty (DMEK) and the need for rebubbling on the contralateral eye.MethodsIn this retrospective cohort study, out of 1541 DMEKs, optical coherence tomography scans and clinical records of 499 eyes undergoing rebubbling after DMEK at the University Hospital of Cologne, Cologne, Germany, were examined. Main Outcome measures were (a) number, localisation and size of graft detachments; (b) influence of rebubbling/s on postoperative outcome after 12 months; and (c) rebubbling risk of the contralateral eye after DMEK.ResultsMean number of detachment areas was 2.02±0.9. Mean lateral diameter of all detachments was 4534.76±1920.83 μm. Mean axial diameter was 382.53±282.02 μm. Detachments were equally distributed over all regions of the cornea. Best spectacle corrected visual acuity ( BSCVA) after 12 months was 0.197±0.23 logarithm of the minimum angle of resolution, endothelial cell density (ECD) was 1575.21±397.71 cells/mm2 and mean central corneal thickness (CCT) was 566.37±68.11 μm. BSCVA, CCT, ECD or endothelial cell loss of all rebubbled patients were not influenced by the number of rebubblings or the time between DMEK and rebubbling. Of the rebubbled patients, which received a DMEK subsequently on the other eye, 193 (58.8%) also received a rebubbling, which was significantly higher, when compared to the overall rebubbling rate of 32.3% (p=0.000).ConclusionsThe overall number of rebubblings has no influence on the postoperative outcome after DMEK, if a rebubbling becomes necessary. Patients who received a rebubbling on one eye have an elevated risk for a rebubbling on the fellow eye.

We measure the willingness to compete of entrepreneurs and salaried workers in an experiment. Participants can choose between a piece rate and a tournament scheme in either private or public. We find that in the private condition, entrepreneurs are less competitive than salaried workers, but in the public condition, this ordering is reversed. Survey data suggest that perceived norms of appropriate behavior, along with beliefs about the instrumental value of competitiveness for professional success, can explain why entrepreneurs are more competitive when decisions are publicly observable. We also find that the latter condition improves the quality of experimental decisions. This paper was accepted by Yan Chen, behavioral economics and decision analysis. Funding: Financial support from the Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany´s Excellence Strategy [Grant EXC 2126/1–390838866], the University of Cologne through the Hans Kelsen Prize and the Austrian Science Fund through the Special Research Area [Grant SFB F63] is gratefully acknowledged. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4838 .