RESUMEN
The study of music has long been of interest to researchers from various disciplines. Scholars have put forth numerous hypotheses regarding the evolution of music. With the rise of cross-species research on music cognition, researchers hope to gain a deeper understanding of the phylogenic evolution, behavioral manifestation, and physiological limitations of the biological ability behind music, known as musicality. This paper presents the progress of beat perception and synchronization (BPS) research in cross-species settings and offers varying views on the relevant hypothesis of BPS. The BPS ability observed in rats and other mammals as well as recent neurobiological findings presents a significant challenge to the vocal learning and rhythm synchronization hypothesis if taken literally. An integrative neural-circuit model of BPS is proposed to accommodate the findings. In future research, it is recommended that greater consideration be given to the social attributes of musicality and to the behavioral and physiological changes that occur across different species in response to music characteristics.
RESUMEN
This multicentre, single arm, phase II study was aimed to assess the efficacy and safety of pazopanib as second-line treatment after failure of sunitinib in patients with metastatic renal cell carcinoma (mRCC) and explore biomarkers for pazopanib response. Patients received pazopanib 800mgperday. The primary end-point was progression-free survival (PFS). Secondary end-points included objective response rate (ORR), overall survival (OS) and safety. Serum proteins (Delta-like ligand (DLL4), Notch1, hypoxia inducible factor-1α (HIF-1α), HIF-2α, vascular endothelial growth factor A (VEGFA) and platelet-derived growth factor receptor ß (PDGFRB)) levels were measured using enzyme-linked immunosorbent assay (ELISA). 86 patients with clear cell mRCC were enrolled from December 2009 to March 2012 from three centres in Southern China. Of 85 evaluable patients, the median PFS was 5.6months (95% confidence interval (CI), 4.1-6.7months) by independent review. No complete response (CR) was observed in all patients. 13 (15.3%; 95% confidence interval [CI], 11.2-23.9%) patients achieved partial responses (PR) (ORR 15.3%). Median OS was 18.1months (95% CI, 13.2-19.8months). The most common adverse events (AEs) were mild to moderate and clinically manageable, including hypertension (37.6%), diarrhoea (36.5%), increased AST (51.8%), and anaemia (60%). AEs resulted in dose reduction in 24.7% of patients. Multivariable analysis showed that higher baseline levels of DLL4 and VEGFA and lower baseline level of HIF-2α were associated with shorter PFS; only lower baseline level of HIF-2α was correlated with shorter OS. The lower expression level of DLL4 after pazopanib treatment was associated with higher response rate probability. In conclusion, pazopanib was clinically active and well tolerated as second-line treatment after sunitinib in mRCC patients. Baseline levels of serum DLL4, VEGFA and HIF-2α may have potential utility as biomarkers of clinical efficacy in this setting (chiCTR-TRC-13004016).