Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma

PURPOSE: Hreceptor (VEGFR) and FGF receptor (FGFR) signaling pathways. EXPERIMENTAL DESIGN: Six different s.c. patient-derived HCC xenografts were implanted into mice. Tumor growth was evaluated in mice treated with brivanib compared with control. The effects of brivanib on apoptosis and cell proliferation were evaluated by immunohistochemistry. The SK-HEP1 and HepG2 cells were used to investigate the effects of brivanib on the VEGFR-2 and FGFR-1 signaling pathways in vitro. Western blotting was used to determine changes in proteins in these xenografts and cell lines. RESULTS: Brivanib significantly suppressed tumor growth in five of six xenograft lines. Furthermore, brivanib-induced growth inhibition was associated with a decrease in phosphorylated VEGFR-2 at Tyr(1054/1059), increased apoptosis, reduced microvessel density, inhibition of cell proliferation, and down-regulation of cell cycle regulators. The levels of FGFR-1 and FGFR-2 expression in these xenograft lines were positively correlated with its sensitivity to brivanib-induced growth inhibition. In VEGF-stimulated and basic FGF stimulated SK-HEP1 cells, brivanib significantly inhibited VEGFR-2, FGFR-1, extracellular signal-regulated kinase 1/2, and Akt phosphorylation. CONCLUSION: This study provides a strong rationale for clinical investigation of brivanib in patients with HCC.

A comparison of alternative bankruptcy prediction models

Early models of bankruptcy prediction employed financial ratios drawn from pre-bankruptcy financial statements and performed well both in-sample and out-of-sample. Since then there has been an ongoing effort in the literature to develop models with even greater predictive performance. A significant innovation in the literature was the introduction into bankruptcy prediction models of capital market data such as excess stock returns and stock return volatility, along with the application of the Black–Scholes–Merton option-pricing model. In this note, we test five key bankruptcy models from the literature using an upto- date data set and find that they each contain unique information regarding the probability of bankruptcy but that their performance varies over time. We build a new model comprising key variables from each of the five models and add a new variable that proxies for the degree of diversification within the firm. The degree of diversification is shown to be negatively associated with the risk of bankruptcy. This more general model outperforms the existing models in a variety of in-sample and out-of-sample tests.

Library and information science education 2.0: guiding principles and models of best practice. Interview with Sue Reynolds.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS educative practice in helping to foster web 2.0 professionals.