Growing our own theatre staff: Practice development and education.

Royal Bournemouth & Christchurch Hospitals NHS Foundation Trust engaged in a quality improvement project aimed at improving quality and safety in theatres. The improvements delivered were recruitment to full staffing template, reduction in agency staffing to zero, and creating a theatre coordinator role to ensure safe staffing. The Practice Education Team was increased fivefold with no extra investment as a result of these improvements.

Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497).

A new series of lactam-derived EZH2 inhibitors was designed via ligand-based and physicochemical-property-based strategies to address metabolic stability and thermodynamic solubility issues associated with previous lead compound 1. The new inhibitors incorporated an sp hybridized carbon atom at the 7-position of the lactam moiety present in lead compound 1 as a replacement for a dimethylisoxazole group. This transformation enabled optimization of the physicochemical properties and potency compared to compound 1.

Discovery of novel, potent, and selective inhibitors of 3-phosphoinositide-dependent kinase (PDK1).

Analogues substituted with various amines at the 6-position of the pyrazine ring on (4-amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)pyrazin-2-ylmethanone were discovered as potent and selective inhibitors of PDK1 with potential as anticancer agents. An early lead with 2-pyridine-3-ylethylamine as the pyrazine substituent showed moderate potency and selectivity. Structure-based drug design led to improved potency and selectivity against PI3Kα through a combination of cyclizing the ethylene spacer into a saturated, five-membered ring and substituting on the 4-position of the aryl ring with a fluorine.

Soil Chemistry in a Loblolly/Longleaf Pine Forest with Interval Burning.

We examined the 30-yr cumulative effects of prescribed fires at intervals of 1, 2, 3, and 4 yr in a loblolly and longleaf pine forest in the Coastal Plain of South Carolina. The fine fraction of the forest floor (Oe + Oa horizons) contained much more carbon and nitrogen per unit area in the control plots (1.7 and 0.