Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours

The expression of additional genes, other than oestrogen receptor (ER), may be important to the hormone-responsive phenotype of breast cancer. Microarray analyses have revealed that forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA-3) are expressed in close association with ERalpha, both encoding for transcription factors with a potential involvement in the ERalpha-mediated action in breast cancer. The purpose of this study was to explore if the expression of FOXA1 and GATA-3 may provide an opportunity to stratify subsets of patients that could have better outcome, among the ERalpha-negative/poor prognosis breast cancer group.The present study was supported by a research grant (SFRH/BD/15316/ 2005 to AA) financed by the Portuguese Science and Technology Foundation (FCT). The authors thank Prof. Raquel Seruca ( coordinator from the Cancer Genetics group at IPATIMUP) for scientific assistance, Dr Jose Luis Costa (postdoctorate at IPATIMUP) for critically reading the manuscript before submission, and Dr Nuno Marcos ( PhD student at IPATIMUP) for artwork assistance

Synergies, Strengths and Challenges: Findings on Community Capability from a Systematic Health Systems Research Literature Review

Background: Community capability is the combined influence of a community’s social systems and collective resources that can address community problems and broaden community opportunities. We frame it as consisting of three domains that together support community empowerment: what communities have; how communities act; and for whom communities act. We sought to further understand these domains through a secondary analysis of a previous systematic review on community participation in health systems interventions in low and middle income countries (LMICs). Methods: We searched for journal articles published between 2000 and 2012 related to the concepts of “community”, “capability/participation”, “health systems research” and “LMIC.” We identified 64 with rich accounts of community participation involving service delivery and governance in health systems research for thematic analysis following the three domains framing community capability. Results: When considering what communities have, articles reported external linkages as the most frequently gained resource, especially when partnerships resulted in more community power over the intervention. In contrast, financial assets were the least mentioned, despite their importance for sustainability. With how communities act, articles discussed challenges of ensuring inclusive participation and detailed strategies to improve inclusiveness. Very little was reported about strengthening community cohesiveness and collective efficacy despite their importance in community initiatives. When reviewing for whom communities act, the importance of strong local leadership was mentioned frequently, while conflict resolution strategies and skills were rarely discussed. Synergies were found across these elements of community capability, with tangible success in one area leading to positive changes in another. Access to information and opportunities to develop skills were crucial to community participation, critical thinking, problem solving and ownership. Although there are many quantitative scales measuring community capability, health systems research engaged with community participation has rarely made use of these tools or the concepts informing them. Overall, the amount of information related to elements of community capability reported by these articles was low and often of poor quality. Conclusions: Strengthening community capability is critical to ensuring that community participation leads to genuine empowerment. Our simpler framework to define community capability may help researchers better recognize, support and assess it

Computed tomography myocardial perfusion vs (15)O-water positron emission tomography and fractional flow reserve

Objectives: Computed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with ¹⁵O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR). Methods: 51 patients (63 (61–65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by “snapshot” adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80. Results: PET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32–2.20) vs 3.11 (2.44–3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32–2.20) vs 3.12 (2.44–3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71–76) vs 86 (84–88) HU, P < 0.001 and 101 (96–106) vs 111 (107–114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR. Conclusion: CT myocardial attenuation density correlates with ¹⁵O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD. Key Points: •CT myocardial perfusion can aid the assessment of suspected coronary artery disease. • CT attenuation density from “snapshot” imaging is a marker of myocardial perfusion. • CT myocardial attenuation density correlates with ¹⁵O-water PET myocardial blood flow. • CT attenuation density is lower in obstructive territories defined by invasive angiography. • Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve