Geographical inequalities in lung cancer management and survival in South East England: evidence of variation in access to oncology services?

This study aimed to determine whether the management and survival of patients with lung cancer varied among 26 health authorities in South East England. The Thames Cancer Registry identified patients diagnosed with lung cancer (ICD-10 codes C33-C34) between 1995 and 1999. After excluding death certificate only patients, 32,818 (81%) patients were analysed. The proportions of patients receiving active treatment varied among health authorities between 5 and 17% for non-investigative surgery, 4 and 17% for any chemotherapy, 8 and 30% for any radiotherapy and 15 and 42% for any active treatment. One-year patient survival ranged from 11 to 34%. There was evidence of health authority level variation even after adjusting for case mix. Patients whose first hospital attendance was at a radiotherapy centre were more likely to receive active treatment (OR 1.72, 95% CI 1.21-2.46), chemotherapy (1.38, 1.06-1.79) or radiotherapy (1.86, 1.28-2.71). There was some evidence that patients whose first hospital attendance was at a radiotherapy centre survived longer. This study shows there is geographical inequality in the treatment given to lung cancer patients and patient survival in South East England. There was some evidence to suggest that these inequalities might be explained by variations in access to oncology services. Future studies should investigate the pathways and barriers to specialist care in this condition

Enabling political legitimacy and conceptual integration for climate change adaptation research within an agricultural bureaucracy: a systemic inquiry

The value of using systems approaches, for situations framed as ‘super wicked’, is examined from the perspective of research managers and stakeholders in a state-based climate change adaptation (CCA) program (CliChAP). Polycentric drivers influencing the development of CCA research pre-2010 in Victoria, Australia are reflected on, using Soft Systems Methodology (SSM) to generate a boundary critique of CCA research as a human activity system. We experienced the complexity of purpose with research practices pulling in different directions, reflected on the appropriateness of agricultural bureaucracies’ historical new public management (NPM) practices, and focused on realigning management theory with emerging demands for adaptation research skills and capability. Our analysis conceptualised CliChAP as a subsystem, generating novelty in a wider system, concerned with socio-ecological co-evolution. Constraining/enabling conditions at the time dealing with political legitimacy and conceptual integration were observed as potential catalysts for innovation in research management towards better handling of uncertainty as a social process using systemic thinking in practice (StiP)

Otitis Media in a New Mouse Model for CHARGE Syndrome with a Deletion in the Chd7 Gene

Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome

Genome-Wide Analysis of Factors Affecting Transcription Elongation and DNA Repair: A New Role for PAF and Ccr4-Not in Transcription-Coupled Repair

RNA polymerases frequently deal with a number of obstacles during transcription elongation that need to be removed for transcription resumption. One important type of hindrance consists of DNA lesions, which are removed by transcription-coupled repair (TC-NER), a specific sub-pathway of nucleotide excision repair. To improve our knowledge of transcription elongation and its coupling to TC-NER, we used the yeast library of non-essential knock-out mutations to screen for genes conferring resistance to the transcription-elongation inhibitor mycophenolic acid and the DNA-damaging agent 4-nitroquinoline-N-oxide. Our data provide evidence that subunits of the SAGA and Ccr4-Not complexes, Mediator, Bre1, Bur2, and Fun12 affect transcription elongation to different extents. Given the dependency of TC-NER on RNA Polymerase II transcription and the fact that the few proteins known to be involved in TC-NER are related to transcription, we performed an in-depth TC-NER analysis of a selection of mutants. We found that mutants of the PAF and Ccr4-Not complexes are impaired in TC-NER. This study provides evidence that PAF and Ccr4-Not are required for efficient TC-NER in yeast, unraveling a novel function for these transcription complexes and opening new perspectives for the understanding of TC-NER and its functional interconnection with transcription elongation