Rotational Spectroscopy of the Acetone-Water Complex: Large Amplitude Motions.

Acetone (CH3COCH3), the simplest ketone, has recently attracted considerable attention for its important role in atmospheric chemistry and in the formation of ices in extraterrestrial sources that contain complex organic molecules. In this study, we employed a combination of experimental rotational spectroscopy and quantum chemistry calculations to investigate the structure and dynamics of the acetone-water complex. Our aim was to understand how non-covalent interactions with water affect the methyl internal rotation dynamics of acetone, and how water-centered large amplitude motions alter the observed physical properties compared to those predicted at the equilibrium position. Detailed rotation-tunneling analyses of acetone-H2O and -D2O reveal that the interactions with water disrupt the equivalence of the two methyl rotors, resulting in a noticeably lower methyl rotor barrier for the top with the close-by water compared to that of free acetone. The barrier for the methyl group further from water is also lower, although to a lesser degree. To gain further insights, extensive theoretical modelling was conducted, focusing on the associated large amplitude motions. Furthermore, quantum theory of atoms in molecules and non-covalent interactions analyses were utilized to visualize the underlying causes of the observed trends.

Risk-adjusted proposal for >60 months follow up after surgical treatment of organ-confined renal cell carcinoma according to life expectancy.

OBJECTIVES: To determine the long-term oncological outcome of organ-confined (

Immune check point inhibitors for metastatic urothelial carcinoma: current evidence-based approach for urology daily practice.

INTRODUCTION: Treatment strategy for inoperable and metastatic urothelial carcinoma (mUC) has been revolutionized by the introduction of programmed cell death protein 1 (PD-1) and programmed cell death protein ligand (PD-L1) antibodies. During the last 3 decades treatment options were limited to chemotherapy, making further treatment of patients whose disease progressed under ongoing therapy or who were ineligible to receive cytotoxic therapy in the first place, nearly impossible. EVIDENCE ACQUISITION: Five antibodies including pembrolizumab (PD-L1 antibody), atezolizumab (PD-1 antibody), nivolumab (PD-1 antibody), avelumab and durvalumab (PD-L1 antibodies) have been approved in the treatment of advanced urothelial carcinoma in first- and second-line treatment setting. The objective of this review was to examine and compare the different cohorts and to discuss the quality of the respective studies in order to set up selection criteria for clinical decision making. EVIDENCE SYNTHESIS: So far pembrolizumab and atezolizumab have demonstrated overall survival (OS) benefit in phase II studies and have shown superiority over standard chemotherapy in phase III studies which has granted them approval in first and second-line treatment setting. Improved OS and durable responses were also seen in phase Ib/II non-randomized, single-arm trials conducted with nivolumab, avelumab and durvalumab and granting accelerated approval for second-line treatment. The huge advantage of immunotherapy and one of the reasons for its overall recognition is its good tolerability profile especially in comparison to chemotherapy. CONCLUSIONS: Pembrolizumab has to be recommended in second-line therapy due to reporting in a phase III trial and OS survival benefit compared to chemotherapy control group. In cisplatin-eligible and treatment-naïve patients with visceral or liver metastases data also slightly favors pembrolizumab rather than atezolizumab.