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To assess safety and ocular hypotensive efficacy of VVN539 ophthalmic solution in a first-in-human study. Multicenter, double-masked, randomized, vehicle-controlled, dose-response, parallel-comparison study. Sixty-eight subjects with ocular hypertension (OHT) or open-angle glaucoma enrolled at 5 private practices. After washout of ocular hypotensive medications as required, the subjects were randomized to receive either VVN539 ophthalmic solution 0.02%, 0.04%, or vehicle once-daily (QD) in the morning (5 days), once-daily in the evening (6 days) and then twice-daily (6 days). Comparison of VVNM539 to its vehicle in mean intraocular pressure (IOP) at each diurnal time point (8:00am, 10:00am, and 4:00pm) at visit 4 (day 7), visit 5 (day 14), and visit 6 (day 21). Mean IOP decreased throughout dosing in the active groups to between 18 and 20 mmHg in both active groups, to between 22 to 23 mmHg in the vehicle group. VVN539 0.04% was statistically superior to vehicle at all 9 diurnal time points (QD AM, QD PM, and twice daily, P ≤ 0.0109). VVN539 0.02% was statistically superior to vehicle at only 6 of 9 diurnal time points (selected QD times and twice daily). The most common ocular treatment-emergent adverse event was conjunctival hyperemia (11 [47.8%], 10 [4.5%], and 1 [4.3%]), followed by ocular hyperemia (3 [13.0%], 5 [22.7%] and 0), respectively. There were no clinically significant changes of note in visual acuity, biomicroscopy, dilated ophthalmoscopy, blood chemistry, hematology, or cardiovascular measures. In conclusion, the results of this initial phase II study indicate that VVN539 ophthalmic solution showed clinically and statistically significant ocular hypertensive activity and was relatively well tolerated for the treatment of subjects with primary open-angle glaucoma or OHT. Additional studies will be required for a more complete evaluation of the utility of VVN539 ophthalmic solution. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Macbeth has been adapted at least fourteen times into eight different opera genres since its being put on the Chinese opera stage in 1980s. As China has become more involved in intercultural communication and international Shakespeare studies, scholars have shown a growing interest in how Chinese traditional opera affects the way Shakespeare is presented. Drawing on interviews with directors and actors, this article examines the differences between Shakespeare's Macbeth and its adaptations in Chinese traditional opera, focusing on three adaptations of Macbeth produced during the last decade in Wu Opera, Hui Opera, and Cantonese Opera. We argue that adaptations of Macbeth into Chinese traditional opera, while having their own interests and distinctive features, limit the exploration of ideas in Macbeth by commenting on the action and applying various operatic strategies and skills to didactic purposes, thus encouraging their audience to interpret the play straightforwardly as a moral fable, a chance to learn more about what is right and what is wrong. In contrast, Shakespeare's play reveals the complexity of human nature, examining human psychology and making no explicit moral judgments of its characters, therefore leaving enough space for the audience's ambivalent response and interpretation. [ABSTRACT FROM AUTHOR]

At the beginning of the design and construction of the STAR Detector, the collaboration assigned a team of physicists and engineers the responsibility of coordinating the construction of the detector. This group managed the general space assignments for each sub-system and coordinated the assembly and planning for the detector. Furthermore, as this group was the only STAR group with the responsibility of looking at the system as a whole, the collaboration assigned it several tasks that spanned the different sub-detectors. These items included grounding, rack layout, cable distribution, electrical, power and water, and safety systems. This paper describes these systems and their performance.