A BRCA1 deficient, NFκB driven immune signal predicts good outcome in triple negative breast cancer

Triple negative (TNBCs) and the closely related Basal-like (BLBCs) breast cancers are a loosely defined collection of cancers with poor clinical outcomes. Both show strong similarities with BRCA1-mutant breast cancers and BRCA1 dysfunction, or 'BRCAness', is observed in a large proportion of sporadic BLBCs. BRCA1 expression and function has been shown in vitro to modulate responses to radiation and chemotherapy. Exploitation of this knowledge in the treatment of BRCA1-mutant patients has had varying degrees of success. This reflects the significant problem of accurately detecting those patients with BRCA1 dysfunction. Moreover, not all BRCA1 mutations/loss of function result in the same histology/pathology or indeed have similar effects in modulating therapeutic responses. Given the poor clinical outcomes and lack of targeted therapy for these subtypes, a better understanding of the biology underlying these diseases is required in order to develop novel therapeutic strategies.We have discovered a consistent NFκB hyperactivity associated with BRCA1 dysfunction as a consequence of increased Reactive Oxygen Species (ROS). This biology is found in a subset of BRCA1-mutant and triple negative breast cancer cases and confers good outcome. The increased NFκB signalling results in an anti-tumour microenvironment which may allow CD8+ cytotoxic T cells to suppress tumour progression. However, tumours lacking this NFκB-driven biology have a more tumour-promoting environment and so are associated with poorer prognosis. Tumour-derived gene expression data and cell line models imply that these tumours may benefit from alternative treatment strategies such as reprogramming the microenvironment and targeting the IGF and AR signalling pathways.

The direction of media influence: Real-estate news and the stock market

This paper uses a novel identification strategy to test the influence of news media on the stock market. Because the stock market does not impact the media coverage of the housing market, a relationship between real-estate news and shares of companies engaged in the housing market is attributable media influence. I find that the content of reporting exhibits a significant relationship with stock returns, and the amount of news with the number of trades. These relationships exist even after controlling for known risk factors, housing market performance and intra-week correlation. This finding is consistent with the function of the media as a source of information and sentiment in financial markets.

Adaptation and Evaluation of the Neighborhood Environment Walkability Scale in India (NEWS-India)

Physical inactivity is the fourth leading risk factor for global mortality, with most of these deaths occurring in low and middle-income countries (LMICs) like India. Research from developed countries has consistently demonstrated associations between built environment features and physical activity levels of populations. The development of culturally sensitive and reliable measures of the built environment is a necessary first step for accurate analysis of environmental correlates of physical activity in LMICs. This study systematically adapted the Neighborhood Environment Walkability Scale (NEWS) for India and evaluated aspects of test-retest reliability of the adapted version among Indian adults. Cultural adaptation of the NEWS was conducted by Indian and international experts. Semi-structured interviews were conducted with local residents and key informants in the city of Chennai, India. At baseline, participants (N = 370; female = 47.2%) from Chennai completed the adapted NEWS-India surveys on perceived residential density, land use mix-diversity, land use mix-access, street connectivity, infrastructure and safety for walking and cycling, aesthetics, traffic safety, and safety from crime. NEWS-India was administered for a second time to consenting participants (N = 62; female = 53.2%) with a gap of 2–3 weeks between successive administrations. Qualitative findings demonstrated that built environment barriers and constraints to active commuting and physical activity behaviors intersected with social ecological systems. The adapted NEWS subscales had moderate to high test-retest reliability (ICC range 0.48–0.99). The NEWS-India demonstrated acceptable measurement properties among Indian adults and may be a useful tool for evaluation of built environment attributes in India. Further adaptation and evaluation in rural and suburban settings in India is essential to create a version that could be used throughout India.