Expression of hypoxia-inducible factor 1 alpha and its downstream targets in fibroepithelial tumors of the breast

INTRODUCTION: Hypoxia-inducible factor 1 (HIF-1) alpha and its downstream targets carbonic anhydrase IX (CAIX) and vascular endothelial growth factor (VEGF) are key factors in the survival of proliferating tumor cells in a hypoxic microenvironment. We studied the expression and prognostic relevance of HIF-1α and its downstream targets in phyllodes tumors and fibroadenomas of the breast. METHODS: The expression of HIF-1α, CAIX, VEGF and p53 was investigated by immunohistochemistry in a group of 37 primary phyllodes tumors and 30 fibroadenomas with known clinical follow-up. The tumor microvasculature was visualized by immunohistochemistry for CD31. Proliferation was assessed by Ki67 immunostaining and mitotic counts. Being biphasic tumors, immunoquantification was performed in the stroma and epithelium. RESULTS: Only two fibroadenomas displayed low-level stromal HIF-1α reactivity in the absence of CAIX expression. Stromal HIF-1α expression was positively correlated with phyllodes tumor grade (P = 0.001), with proliferation as measured by Ki67 expression (P < 0.001) and number of mitoses (P < 0.001), with p53 accumulation (P = 0.003), and with global (P = 0.015) and hot-spot (P = 0.031) microvessel counts, but not with CAIX expression. Interestingly, concerted CAIX and HIF-1α expression was frequently found in morphologically normal epithelium of phyllodes tumors. The distance from the epithelium to the nearest microvessels was higher in phyllodes tumors as compared with in fibroadenomas. Microvessel counts as such did not differ between fibroadenomas and phyllodes tumors, however. High expression of VEGF was regularly found in both tumors, with only a positive relation between stromal VEGF and grade in phyllodes tumors (P = 0.016). Stromal HIF-1α overexpression in phyllodes tumors was predictive of disease-free survival (P = 0.032). CONCLUSION: These results indicate that HIF-1α expression is associated with diminished disease-free survival and may play an important role in stromal progression of breast phyllodes tumors. In view of the absence of stromal CAIX expression in phyllodes tumors, stromal upregulation of HIF-1α most probably arises from hypoxia-independent pathways, with p53 inactivation as one possible cause. In contrast, coexpression of HIF-1α and CAIX in the epithelium in phyllodes tumors points to epithelial hypoxia, most probably caused by relatively distant blood vessels. On the other hand, HIF-1α and CAIX seem to be of minor relevance in breast fibroadenomas

A novel approach for prediction of vitamin D status using support vector regression

Background: Epidemiological evidence suggests that vitamin D deficiency is linked to various chronic diseases. However direct measurement of serum 25-hydroxyvitamin D (25(OH)D) concentration, the accepted biomarker of vitamin D status, may not be feasible in large epidemiological studies. An alternative approach is to estimate vitamin D status using a predictive model based on parameters derived from questionnaire data. In previous studies, models developed using Multiple Linear Regression (MLR) have explained a limited proportion of the variance and predicted values have correlated only modestly with measured values. Here, a new modelling approach, nonlinear radial basis function support vector regression (RBF SVR), was used in prediction of serum 25(OH)D concentration. Predicted scores were compared with those from a MLR model. Methods: Determinants of serum 25(OH)D in Caucasian adults (n = 494) that had been previously identified were modelled using MLR and RBF SVR to develop a 25(OH)D prediction score and then validated in an independent dataset. The correlation between actual and predicted serum 25(OH)D concentrations was analysed with a Pearson correlation coefficient. Results: Better correlation was observed between predicted scores and measured 25(OH)D concentrations using the RBF SVR model in comparison with MLR (Pearson correlation coefficient: 0.74 for RBF SVR; 0.51 for MLR). The RBF SVR model was more accurately able to identify individuals with lower 25(OH)D levels

Sustainability, lean, green and eco-efficiency symbioses

A literature review was conducted aiming at investigating the use of Sustainability, Lean, Green and eco-efficiency concepts, as well as meaningful combinations of those, on the field of Production and Operations Management. The study reports on the scientific papers published in all major journals in the field over the period 2001–2015. A set of 83 papers from 40 journals were selected for further analyzes, aiming at uncovering the existing level of awareness and use of the synergic and symbiotic relationship between Lean Manufacturing and Green Production. The findings show that a modest share of papers, about 30 %, explicitly recognize the Lean-Green joint approach. The same study testifies a clear growth pattern, which is patently reinforced in the last two and a half years, on the number of papers that behold a combined approach towards more efficient and cleaner production activities. The research has highlighted that the Lean-Green link does, in fact, exist and is gaining momentum, but requires further reinforcements from the scientific community, as well as from the companies, to deliver excelled and environmentally sound production systems.FCT Strategic Project PEst2015-2020, reference UID/CEC/00319/2013.info:eu-repo/semantics/publishedVersio

Work–life programs and performance in Australian organisations: the role of organisation size and industry type

Organisations are increasingly using work–life programs to strategically manage their workforce in a competitive labour market. Extant research has investigated various outcomes of work–life programs but has lacked focus on organisational financial performance and context. Drawing on strategic human resource management theory, this study proposes and tests a work–life programs–performance relationship. It also investigates the moderating effects of organisation size and industry on the work–life programs–performance relationship. We used a time-lagged design and data from multiple sources to link work–life programs with firm performance in 117 organisations in Australia. The findings support the hypothesis that work–life programs are positively associated with financial performance. This study also provides pioneering evidence for the moderating effects of organisation size and industry type on the work–life programs–organisational performance relationship.</p