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Insulin-like growth factor binding protein 2 (IGFBP-2) as prognostic parameter in infarct-related cardiogenic shock
No full textBackgroundCardiogenic shock (CS) caused by acute myocardial infarction (AMI) is a critical condition with high mortality rate. Insulin-like growth factor binding protein 2 (IGFBP-2) is dysregulated in cardiovascular diseases. The purpose of the present study was to investigate the prognostic value of IGFBP-2 in patients with AMI-CS.MethodsThis study is a post-hoc analysis of the randomized multicentre CULPRIT-SHOCK trial. IGFBP-2 levels were measured in serum samples from 423 patients using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Associations of IGFBP-2 with 30-day and one-year mortality were investigated.ResultsMedian IGFBP-2 concentration was 415 ng/ml (IQR 274–699 ng/ml). Patients with IGFBP-2 ≥ median demonstrated higher 30-day (54 % vs. 37 %; p ConclusionsIn AMI-CS, elevated levels of IGFBP-2 were associated with higher mortality at 30 days and one year after admission. IGFBP-2 represents a promising prognostic biomarker and could add value to risk stratification in this high-risk patient cohort, potentially informing early clinical decision-making
Propensity-matched comparison of proximal versus distal shunt insertion during eversion carotid endarterectomy of the internal carotid artery in symptomatic and asymptomatic patients
No full textBackgroundThe aim of this study was to compare the 2 intraoperative shunting techniques (proximal vs. distal) during eversion endarterectomy (EEA) of the internal carotid artery (ICA).MethodsAll patients operated between January 2011 and December 2022 who received routine shunting of the ICA were enrolled in this retrospective study. Patients undergoing selective shunting, patch angioplasty of the ICA, redo surgeries, or surgery performed by a resident were excluded. Intraoperative shunt placement took place after completing the eversion of the ICA. The patients were divided into 2 groups based on shunt placement technique: (i) distal shunting, where the shunt was firstly inserted into the ICA and then into the common carotid artery, and (ii) proximal shunting, where the shunt was firstly inserted into the common carotid artery and then into the ICA. Propensity score matching was used to compare the 2 groups. All procedures were performed under general anesthesia, with regional cerebral oxygenation monitoring. The primary end point was the incidence of perioperative stroke and in-hospital mortality.ResultsA total of 658 thromboendarterectomies of the ICA using intraoperative shunt were performed during the study period. Proximal shunting was used in 330 (50.2%) and distal shunting in 328 (49.8%). Using the propensity score matching, 260 pairs were generated for analysis. The perioperative stroke rate was significantly higher in the proximal shunting group, n = 13 (5%), compared to the distal shunting group, n = 4 (1.5%), (P ConclusionIn the setting of an elective shunting of the ICA during EEA, the proximal first placement of the shunt may cause a higher incidence of perioperative stroke compared to the distal first placement of the stunt. A distal first shunting strategy seems reasonable when performing EEA surgery to improve patient outcomes
Quantification of the sulfur strand length distribution in organo-sulfur cathode materials with X-ray absorption spectrometry
No full textTherapeutic targeting of chromatin alterations in leukemia and solid tumors
No full textAlterations in chromatin conformation and post-translational modification of histones have become increasingly recognized as critical drivers of cancer development, progression, and therapy resistance. Recent advances in drug development have led to the establishment of several highly selective small molecule inhibitors, several of which are currently under investigation in clinical trials. These compounds allow the precise interrogation of specific chromatin features and functions, transforming the field of epigenetic cancer therapy from rather unselective approaches, like histone deacetylase inhibition or demethylating agents, toward the use of true targeted therapeutics. Recently, several compounds altering histone methylation have been investigated in preclinical and clinical trials. We summarize the current state of development for inhibitors against Menin-KMT2A, DOT1L, KDM1A, and Polycomb complexes, and the arginine methyltransferase PRMT5 for the treatment of myeloid malignancies, lymphoma, and different solid tumors. Inhibitors of IDH1/2 act at the interface of epigenetic and metabolic vulnerabilities and have been FDA-approved for the treatment of IDH-mutant glioma, cholangiocarcinoma, and myeloid malignancies. Several clinical trials investigating effective combination therapy regimens are ongoing and summarized herein. Drugs targeting components of SWI/SNF chromatin remodeling complexes, such as inhibitors of SMARCA4, have entered the clinic. Members of SWI/SNF complexes are among the most frequently mutated genes across all cancer entities, and novel selective inhibitors for the first time allow pharmacologic interrogation of aberrant chromatin remodeling. Overall, the therapeutic interrogation of chromatin-related processes plays an increasing role in cancer therapy. This chapter reviews recent developments and future directions in the field of epigenetic cancer therapy
Menschenrechte als Maßstab für das globale Steuersystem
No full textDie extraterritorialen Auswirkungen von Steuersystemen sind seit den „Panama Papers" ein kontrovers diskutierter Bereich, der bedeutende Regulierungsbemühungen nach sich gezogen hat. Kaum diskutiert wurde bislang die Frage, wie die im globalen Steuersystem bestehenden Probleme - etwa des „schädlichen Steuerwettbewerbs" - aus menschenrechtlicher Sicht zu bewerten sind. Silke Weller untersucht Phänomene der internationalen Steuerpolitik vor dem Hintergrund der Debatte um extraterritoriale Staatenpflichten und fragt, inwiefern sich steuerpolitische Verhaltensweisen mit extraterritorialen Auswirkungen als Verletzung von Menschenrechtsverträgen einordnen lassen und welche Konsequenzen aus einer solchen „Humanisierung" internationaler Steuerpolitik folgen könnten
Critical contributions of gender perspectives for transformative adaptation planning : a case study from Southern Germany
No full textClimate change adaptation decisions profoundly impact resource distribution and future pathways, yet empirical research that critically examines power dynamics and injustices in adaptation processes in the Global North remains limited. We argue that gender perspectives offer a valuable analytical lens to understanding and addressing the politics of adaptation and demonstrate this through a retrospective analysis of a municipal adaptation planning process in Southern Germany. Combining gender perspectives with the trivalent environmental justice framework, we show how municipal adaptation planning in Germany affects and reflects gender relations. The findings point to the androcentric narratives that suppress feminized knowledges and epistemologies as well as to the gendered norms and practices that dominate municipal adaptation planning. Finally, we discuss how these findings can inform transformative adaptation, for example by emphasizing the need for more inclusive participatory methods in adaptation processes
Why personnel selection should target job performance and well‐being
No full textIn this “Provocation Article”, we argue that the sole focus of personnel selection research and practice on job performance criteria represents a substantial limitation. While job performance remains a key outcome, employee well-being is also relevant—both as an intrinsic value and as a predictor of important organizational outcomes such as turnover, absenteeism, and citizenship behavior. Given the solid evidence on individual differences and work-related factors that influence employee well-being, and drawing on ethical, legal, and economic arguments, we call for a paradigm shift: Well-being should be treated as an explicit criterion in personnel selection. We outline five practical pathways for integrating well-being into selection systems, including the use of well-being-related traits (which should be carefully matched to job-specific demands), person–environment fit approaches, simulation-based tools, communicating well-being priorities to applicants, and using selection insights to inform onboarding and support. We also discuss four key challenges, such as the risk of discriminatory practices, balancing multiple criteria, and faking. Finally, we sketch a research agenda to guide future work on well-being-focused selection. Overall, we advocate for multi-criteria selection systems that promote not only organizational performance but also human flourishing
