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3537Background: Patients with mCRC are typically offered chemotherapy and might also receive target therapy-drugs targeting VEGF or EGFR. In phase 3 FRESCO trial, fruquintinib demonstrated a statis...

UNLABELLED Inhaled umeclidinium (UMEC) and the combination of inhaled UMEC with vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease in the US and EU. This was a randomized, open-label, three-period crossover, single- and repeat-dose study to assess the pharmacokinetics (PK), safety, and tolerability of inhaled UMEC/VI 62.5/25 μg (delivering 55/22 μg) and UMEC/VI 125/25 μg (delivering 113/22 μg) compared with their monotherapy components (UMEC 62.5 μg, UMEC 125 μg and, VI 25 μg [delivering 55, 113, and 22 μg, respectively]) in healthy Chinese subjects (n=20). UMEC and VI were rapidly absorbed following single and repeat dosing (time to maximum plasma concentration [tmax]: UMEC = 5 min; VI = 5 min). The median tlast was 2–4 h for UMEC and 1–2 h for VI following single doses of UMEC/VI and UMEC monotherapy (both doses). UMEC reached steady-state prior to Day 10; steady-state for VI could not be assessed. UMEC accumulation following repeat dosing was 11–34% based on Cmax and 19–59% based on area under the concentration-time curve from time zero to 2 h (AUC(0-2)). VI accumulation following repeat dosing was 25–66% based on Cmax and 17–43% based on AUC(0-2). The evidence was not sufficient to suggest that systemic exposure was substantially different between UMEC/VI combination therapy and the constituent monotherapies following single or repeat dosing. Following both single- and repeat-dose administration, the inter-subject coefficient of variation for all UMEC PK parameter estimates ranged from 12% to 165% for all treatments, indicating a wide range of variability in inhaled PK parameters. Twelve subjects experienced ≥1 adverse event (AE). Six subjects experienced ≥1 treatment-related AE; the most commonly reported treatment-related AE was chest discomfort (n=3 [15%]). No clinically important changes in vital signs or electrocardiogram parameters were reported. These data suggest that single- and repeat-dose administration of UMEC/VI combination therapy in healthy Chinese subjects did not result in substantial differences in systemic exposure compared with UMEC and VI as monotherapies. TRIAL REGISTRATION Clinicaltrials.gov NCT01899638 NCT01899638.

An improved structure for the sound coil of loudspeaker comprises a cylinder provided with multiple layers of coils surrounding one end thereon. The coils are divided into sections in the middle position which provide more than two conducting wires. The cylinder is rolled by a single plate and is provided with four layers of coils. The conducting wire extends to the other end of cylinder and is wrapped with oilpaper; and connects to a piece of thick wire. The cylinder is provided with several ventilation holes. Every two layers of coil being a independent wire material, the sound coil comprised four conducting wires; or each layer of coil being a independent wire material, the sound coil comprised eight conducting wires. Thus the sound coil produces larger output power and reduces the size of sound coil, the coils surrounding the cylinder, production costs, and the size of products.

The invention comprises a supporting stand provided with an enlarged opening in the front and a damper in the rear for adhering to the sound coil; a magnetic circuit supported by a cylinder and connecting to the supporting stand and both ends of the magnetic circuit are provided with movement-accommodating space; first sound coil provided in the movement-accommodating space on one end of the magnetic circuit; second sound coil provided in the movement-accommodating space on the other end of the magnetic circuit; first diaphragm provided in the inner rim of the enlarged opening and adhering to the first sound coil; and second diaphragm provided in the inner rim of magnetic circuit and adhering to second sound coil; thereby allows the magnetic circuit to be installed in front of the supporting stand; and thus outputs high-pitch sound and low-pitch sound simultaneously from a single device.

A yoke structure of a speaker diaphragm comprises a casing having a front side being installed with an enlarged opening and rear side thereof being installed with a magnetic element; a coil being placed in the magnetic element; a damper being engaged with the coil; and a diaphragm being placed at the enlarged opening of the casing and being sticky to the coil, and a diaphragm being placed at the enlarged opening of the casing and being sticky to the coil. In the present invention, a yoke portion with two layer curved portions is placed between the casing and the diaphragm; the yoke portion is made of elastic material and has front and a rear layer, and each layer is formed with bent arcs. As a result, the diaphragm can be assembled conveniently at one time and is adhered well. Moreover, the center thereof can be positioned preferably. Thus, the output of the speaker will avoid interference from the vibration of the diaphragm. Therefore, the work of the yoke portion and the sound wave are more harmonic and as a result, a better sound quality is acquired.