Characterisation of respiratory mechanics in adults with CF using dynamic chest radiography.

Background: As the lifespan of people with CF (pwCF) improves, sensitive markers of lung health are needed. Dynamic chest radiography (DCR) is a low ionising radiation dose cineradiographic imaging system that provides real-time information on moving thoracic structures. We examined whether DCR provides quantitative motion analysis that correlates with pulmonary function, anthropometric and clinical variables in pwCF, to explore DCR as a marker of lung health.

Aurora B inhibition induces hyper-polyploidy and loss of long-term proliferative potential in RB and p53 defective cells.

Polyploidy is a common outcome of chemotherapies, but there is conflicting evidence as to whether polyploidy is an adverse, benign or even favourable outcome. We show Aurora B kinase inhibitors efficiently promote polyploidy in many cell types, resulting in the cell cycle exit in RB and p53 functional cells, but hyper-polyploidy in cells with loss of RB and p53 function. These hyper-polyploid cells (>8n DNA content) are viable but have lost long-term proliferative potential in vitro and fail to form tumours in vivo.

Aurora B inhibitors promote RB hypophosphorylation and senescence independent of p53-dependent CDK2/4 inhibition.

Aurora B kinase (AURKB) inhibitors have been trialled in a range of different tumour types but are not approved for any indication. Expression of the human papilloma virus (HPV) oncogenes and loss of retinoblastoma (RB) protein function has been reported to increase sensitivity to AURKB inhibitors but the mechanism of their contribution to sensitivity is poorly understood. Two commonly reported outcomes of AURKB inhibition are polyploidy and senescence, although their relationship is unclear.

Regulatory adverse drug reaction analyses support a temporal increase in psychiatric reactions after initiation of cystic fibrosis combination modulator therapies.

Introduction: Despite improved outcomes for many people with cystic fibrosis, there have been reports of adverse neuropsychiatric effects of modulator therapy. The aim of this research is to define temporal associations in adverse drug reaction (ADR) reports for available CFTR modulators.

Methods: Methods include an analysis of the UK Yellow Card Scheme data for ADRs through accessing interactive Drug Analysis Profiles (iDAPs) to define temporal trends in absolute and proportional counts.