Diversity of US participants in AstraZeneca-sponsored clinical trials.

Background: To develop medicines that are safe and efficacious to all patients, clinical trials must enroll appropriate target populations, but imbalances related to race, ethnicity and sex have been reported. A comprehensive analysis and improvement in understanding representativeness of patient enrollment in industry-sponsored trials are key public health needs.

Methods: We assessed race/ethnicity and sex representation in AstraZeneca (AZ)-sponsored clinical trials in the United States (US) from 2010 to 2022, compared with the 2019 US Census.

Longitudinal trends of peripheral blood counts in polycythaemia vera and essential thrombocythemia patients in the UK.

There is sparse evidence of how well haematological targets are met in practice for essential thrombocythemia (ET) and polycythaemia vera (PV) patients. Patient data was collected between 2008 and 2020 from two UK NHS Trusts for ET and PV patients. Longitudinal changes in peripheral blood counts, including the proportion of patients meeting peripheral blood count remission, was modelled.

Directly imaging the localisation and photosensitization properties of the pan-mTOR inhibitor, AZD2014, in living cancer cells.

The range of cellular functions the mechanistic target of rapamycin (mTOR) protein performs makes it an attractive drug target for cancer therapy. However, the cellular localisation and mode of action of second generation inhibitors of mTOR is poorly understood despite the level of attention there is in targeting the mTOR protein. We have therefore studied the properties of the pan-mTOR inhibitor AZD2014, an ideal candidate to study because it is naturally fluorescent, characterising its photochemical properties in solution phase (DMSO, PBS and BSA) and within living cells, where it localises within both the nucleus and the cytoplasm but with different excited state lifetimes of 4.

TRACKING DOWN ALPHA-PARTICLES: THE DESIGN, CHARACTERISATION AND TESTING OF A SHALLOW-ANGLED ALPHA-PARTICLE IRRADIATOR.

Human exposure to α-particles from radon and other radionuclides is associated with carcinogenesis, but if well controlled and targeted to cancer cells, α-particles may be used in radiotherapy. Thus, it is important to understand the biological effects of α-particles to predict cancer risk and optimise radiotherapy. To enable studies of α-particles in cells, we developed and characterised an α-particle automated irradiation rig that allows exposures at a shallow angle (70° to the normal) of cell monolayers in a 30 mm diameter dish to complement standard perpendicular irradiations.

Super-Resolution Nanoscopy Imaging Applied to DNA Double-Strand Breaks.

Genomic deoxyribonucleic acid (DNA) is continuously being damaged by endogenous processes such as metabolism or by exogenous events such as radiation. The specific phosphorylation of histone H2AX on serine residue 139, described as γ-H2AX, is an excellent indicator or marker of DNA double-strand breaks (DSBs). The yield of γ-H2AX (foci) is shown to have some correlation with the dose of radiation or other DSB-causing agents.