The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With at Least Two Tyrosine Kinase Inhibitors

Asciminib is an allosteric high-affinity tyrosine kinase inhibitor (TKI) of the BCR-ABL1 protein kinase. This kinase is translated from the Philadelphia chromosome in chronic myeloid leukemia (CML). Marketing authorization for asciminib was granted on August 25, 2022 by the European Commission. The approved indication was for patients with Philadelphia chromosome-positive CML in the chronic phase which have previously been treated with at least 2 TKIs. Clinical efficacy and safety of asciminib were evaluated in the open-label, randomized, phase III ASCEMBL study. The primary endpoint of this trial was major molecular response (MMR) rate at 24 weeks. A significant difference in MRR rate was shown between the asciminib treated population and the bosutinib control group (25.5% vs. 13.2%, respectively, P=.029). In the asciminib cohort, adverse reactions of at least grade 3 with an incidence≥5% were thrombocytopenia, neutropenia, increased pancreatic enzymes, hypertension, and anemia. The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the European Medicines Agency's Committee for Medicinal Products for Human Use.</p

Experimental and quantum chemical studies of anionic analogues of N-heterocyclic carbenes.

A combination of quantum chemical and synthetic/crystallographic methods have been employed to probe electronic structure in two series of anionic ligands related to the well known N-heterocyclic carbene (NHC) class of donor. Analyses of (i) the respective frontier orbital energies/compositions for the 'free' ligands and the results of ETS-NOCV studies of the bonding in model group 11 complexes; and (ii) the structural metrics for (new) linear gold(i) compounds, have been used to probe the bonding in complexes of NHC ligands which incorporate a backbone-appended weakly-coordinating anion component (WCA-NHCs) and in systems featuring the isoelectronic (formally anionic) diazaborolyl ligand family. Key findings are that WCA-NHC ligands - in which the anionic component is attached to the ligand heterocycle via a methylene (CH2) spacer - offer electronic (and steric) properties which are largely unperturbed from their 'simple' NHC counterparts, while diazaborolyl donors (in which the negative charge is formally located at the boron donor atom) offer significantly stronger σ-donation and a very high trans influence

Experimental and quantum chemical studies of anionic analogues of N-heterocyclic carbenes.

A combination of quantum chemical and synthetic/crystallographic methods have been employed to probe electronic structure in two series of anionic ligands related to the well known N-heterocyclic carbene (NHC) class of donor. Analyses of (i) the respective frontier orbital energies/compositions for the 'free' ligands and the results of ETS-NOCV studies of the bonding in model group 11 complexes; and (ii) the structural metrics for (new) linear gold(i) compounds, have been used to probe the bonding in complexes of NHC ligands which incorporate a backbone-appended weakly-coordinating anion component (WCA-NHCs) and in systems featuring the isoelectronic (formally anionic) diazaborolyl ligand family. Key findings are that WCA-NHC ligands - in which the anionic component is attached to the ligand heterocycle via a methylene (CH2) spacer - offer electronic (and steric) properties which are largely unperturbed from their 'simple' NHC counterparts, while diazaborolyl donors (in which the negative charge is formally located at the boron donor atom) offer significantly stronger σ-donation and a very high trans influence

Personalmanagement

Auch wenn der Wert in keiner Bilanz auftaucht: das Humankapital entscheidet über den Unternehmenserfolg. Während Kapital im Überfluss vorhanden ist, ist das Personal zunehmend der Engpassfaktor. Wurde bis in die 1980er-Jahre der Mensch als Produktionsfaktor und die Personalabteilung als seine Verwaltungsinstanz gesehen, so ist die Personalarbeit heute ein integratives Element des Managementprozesses und die Personalabteilung aktiver Teil des Managementteams (Scholz 2014c). Damit verbunden ist der begriffliche Wandel von Personalwirtschaft bzw. Personalverwaltung hin zum Personalmanagement bzw. Human Ressource Management (HRM). Die Begriffe signalisieren eine stärker strategisch ausgerichtete Auseinandersetzung mit allen Fragen, die den Einsatz von Personal und die Verknüpfung der Personal- mit der Unternehmensstrategie zum Gegenstand haben. Wichtige Aufgaben der Personalarbeit sind Personalplanung, Personalbeschaffung, Personalentwicklung, Personaleinsatz, Personalkostenmanagement, Personalführung. Diese werden in der Regel von unterschiedlichen Stellen wahrgenommen – neben der Personalabteilung spielen dabei auch die direkte Führungskraft sowie die Unternehmensleitung eine wichtige Rolle