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Abstract: Background: The safety and efficacy of neratinib monotherapy were compared with that of lapatinib plus capecitabine in patients with human epidermal growth factor receptor-2-positive (HER2+), locally advanced/metastatic breast cancer and prior trastuzumab treatment. Methods: Patients received neratinib 240mg/d continuously (n =117) or lapatinib 1250mg/d continuously plus capecitabine 2000mg/m2 per day on days 1–14 of each 21-d cycle (n =116). The primary aim was to demonstrate non-inferiority of neratinib for progression-free survival (PFS). Findings: The non-inferiority of neratinib was not demonstrated when compared with lapatinib plus capecitabine (hazard ratio, 1.19; 95% confidence interval, 0.89–1.60; non-inferiority margin, 1.15). Median PFS for neratinib was 4.5months versus 6.8months for lapatinib plus capecitabine and median overall survival was 19.7months versus 23.6months. Objective response rate (neratinib, 29% versus lapatinib plus capecitabine, 41%; P =0.067) and clinical benefit rate (44% versus 64%; P =0.003) were lower for the neratinib arm but consistent with previously reported results. In both treatment arms, diarrhoea was the most frequently reported treatment-related adverse event of any grade (neratinib, 85% versus lapatinib plus capecitabine, 68%; P =0.002) and of grade 3/4 (28% versus 10%; P <0.001), but was typically managed with concomitant anti-diarrhoeal medication and/or study treatment modification. Importantly, neratinib had no significant skin toxicity. Interpretation: The results are considered as inconclusive since neither inferiority nor non-inferiority of treatment with neratinib versus lapatinib plus capecitabine could be demonstrated. The study confirmed relevant single-agent clinical activity and acceptable overall tolerability of neratinib in patients with recurrent HER2+ advanced breast cancer. [Copyright &y& Elsevier]

: BackgroundIn this study, the magnitude and spatial distribution of beta power in the resting electroencephalogram (EEG) were examined to address the possibility of an excitation–inhibition imbalance in the central nervous system of alcoholics.: MethodsLog transformed absolute power in the Beta 1 (12.5–16 Hz), Beta 2 (16.5–20 Hz), and Beta 3 (20.5–28 Hz) bands in the eyes-closed EEG of 307 alcohol-dependent subjects and 307 unaffected age- and gender-matched control subjects were compared using a multivariate repeated measures design. Effect of gender, age, and drinking variables was examined separately.: ResultsIncreased Beta 1 (12.5–16 Hz) and Beta 2 (16.5–20 Hz) absolute power was observed in alcohol-dependent subjects at all loci over the scalp. The increase was most prominent in the central region. Increased Beta 3 (20.5–28 Hz) power was frontal in the alcoholics. Age and clinical variables did not influence the increase. Male alcoholics had significantly higher beta power in all three bands. In female alcoholics the increase did not reach statistical significance.: ConclusionsBeta power in all three bands of resting EEG is elevated in alcoholics. This feature is more prominent in male alcoholics. The increased beta power in the resting EEG may be an electrophysiological index of the imbalance in the excitation–inhibition homeostasis in the cortex. [ABSTRACT FROM AUTHOR]