Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials.

AimsThis analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials.Materials and methodsData from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo-controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe-controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin. Alirocumab 75/150 mg indicates possible dose increase from 75 to 150 mg at Week 12 based on Week 8 LDL-C.ResultsLDL-C percentage reduction from baseline at Week 24 with alirocumab was 63.9% (MetS) and 56.8% (non-MetS) in the pool of alirocumab 150 mg Q2W, and 42.2% to 52.2% (MetS) and 45.0% to 52.6% (non-MetS) in 3 pools using 75/150 mg Q2W. Levels of other lipid and lipoprotein parameters were also improved with alirocumab treatment, including apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) and HDL-C. Overall, the percentage change at Week 24 in LDL-C and other lipids and lipoproteins did not vary by MetS status. Adverse event rates were generally similar between treatment groups, regardless of MetS status; injection-site reactions occurred more frequently in alirocumab vs control groups.ConclusionsAcross study pools, alirocumab-associated reductions in LDL-C, apolipoprotein B, and non-HDL-C were significant vs control, and did not vary by MetS status

Measurements of noise in Josephson-effect mixers

We present new heterodyne receiver results obtained at 100 GHz using resistively-shunted Nb and NbN tunnel junctions. In addition, we have carried out accurate measurements of the available noise power of these devices at the L-band (1.5 GHz) IF frequency. Both the heterodyne and the output noise measurements show that the noise of these devices can be a factor of five or more higher than that predicted by the simple current-biased RSJ model. The noise approaches the appropriate thermal or thermal and shot noise limits for bias voltages where the nonlinearity is not strong (i.e., V>ICRN), but as expected from the RSJ model, can be significantly higher at the low voltages where the mixers are typically biased. The bias voltage dependence of the noise shows structure which is associated with resonances in the RF embedding circuit. Surprisingly, we find that changes in the high-frequency (100 GHz) impedance presented to the junction can dramatically affect the magnitude and voltage dependence of the low-frequency (1.5 GHz) noise. This emphasizes the necessity of very closely matching the junction to free space over a wide frequency range

Inactivation of cloned Na channels expressed in Xenopus oocytes

This study investigates the inactivation properties of Na channels expressed in Xenopus oocytes from two rat IIA Na channel cDNA clones differing by a single amino acid residue. Although the two cDNAs encode Na channels with substantially different activation properties (Auld, V. J., A. L. Goldin, D. S. Krafte, J. Marshall, J. M. Dunn, W. A. Catterall, H. A. Lester, N. Davidson, and R. J. Dunn. 1988. Neuron. 1:449-461), their inactivation properties resemble each other strongly but differ markedly from channels induced by poly(A+) rat brain RNA. Rat IIA currents inactivate more slowly, recover from inactivation more slowly, and display a steady-state voltage dependence that is shifted to more positive potentials. The macroscopic inactivation process for poly(A+) Na channels is defined by a single exponential time course; that for rat IIA channels displays two exponential components. At the single-channel level these differences in inactivation occur because rat IIA channels reopen several times during a depolarizing pulse; poly(A+) channels do not. Repetitive stimulation (greater than 1 Hz) produces a marked decrement in the rat IIA peak current and changes the waveform of the currents. When low molecular weight RNA is coinjected with rat IIA RNA, these inactivation properties are restored to those that characterize poly(A+) channels. Slow inactivation is similar for rat IIA and poly(A+) channels, however. The data suggest that activation and inactivation involve at least partially distinct regions of the channel protein

Cottontail Rabbit Habitat Use on Delaware Wildlife Area, Ohio

Author Institution: Ohio Department of Natural Resources, Division of WildlifeA radio telemetry study was performed on cottontail rabbits (Sylvilagus floridanus mearnsii) to quantify cover type use and infer selections with respect to cover type availability, year, sex- and age-class, time of day, and season. This study recorded 16,785 locations for 62 rabbits from 1981-1983. Briars (Rubus spp., Rosa multiflord) and old field were the two most used types of cover, together comprising more than 50% of locations. Relative to cover type availability, the briars type was the most preferred (P < 0.05). Both types were used heavily during day and night throughout the year, although use of briars was higher during day than night (P < 0.05). Rabbits that had survived a winter and spring spent more time in briars (P < 0.05) and less time in old field OP < 0.05) than those that had not. Implications are that wildlife managers must increase their emphasis on providing briars or other dense woody vegetation to maintain rabbit populations. Based on use percentages, rabbit cover type needs would be better met if percentages of area were: briars, herb-shrub, and cropland — each 25-35%; woodland — 0-10%

Alignment-insensitive coupling for PLC-based surface mount photonics

A flip-chip waveguide coupler with an order of magnitude greater alignment tolerance than competing approaches is presented for the first time. Experimental data for an "optical jumper" agree with simple design considerations. Application to a planar lightwave circuit-based surface mount photonics platform is outlined