196,287 research outputs found
Alirocumab efficacy in patients with double heterozygous, compound heterozygous, or homozygous familial hypercholesterolemia
No full textBackground: Mutations in the genes for the low-density lipoprotein receptor (LDLR), apolipoprotein B, and proprotein convertase subtilisin/kexin type 9 have been reported to cause heterozygous and homozygous familial hypercholesterolemia (FH). Objective: The objective is to examine the influence of double heterozygous, compound heterozygous, or homozygous mutations underlying FH on the efficacy of alirocumab. Methods: Patients from 6 alirocumab trials with elevated low-density lipoprotein cholesterol (LDL-C) and FH diagnosis were sequenced for mutations in the LDLR, apolipoprotein B, proprotein convertase subtilisin/kexin type 9, LDLR adaptor protein 1 (LDLRAP1), and signal-transducing adaptor protein 1 genes. The efficacy of alirocumab was examined in patients who had double heterozygous, compound heterozygous, or homozygous mutations. Results: Of 1191 patients sequenced, 20 patients were double heterozygotes (n = 7), compound heterozygotes (n = 10), or homozygotes (n = 3). Mean baseline LDL-C levels were similar between patients treated with alirocumab (n = 11; 198 mg/dL) vs placebo (n = 9; 189 mg/dL). All patients treated with alirocumab 75/150 or 150 mg every 2 weeks had an LDL-C reduction of ≥15% at either week 12 or 24. At week 12, 1 patient had an increase of 7.1% in LDL-C, whereas in others, LDL-C was reduced by 21.7% to 63.9% (corresponding to 39–114 mg/dL absolute reduction from baseline). At week 24, LDL-C was reduced in all patients by 8.8% to 65.1% (10–165 mg/dL absolute reduction from baseline). Alirocumab was generally well tolerated in the 6 trials. Conclusion: Clinically meaningful LDL-C–lowering activity was observed in patients receiving alirocumab who were double heterozygous, compound heterozygous, or homozygous for genes that are causative for FH
Effective securities in arbitrage-free markets with bid-ask spreads at liquidation: a linear programming characterization
No full textWe consider a securities market with bid–ask spreads at any period, including liquidation. Although the minimum-cost super-replication problem is non-linear, we introduce an auxiliary problem that allows us to characterize no-arbitrage via linear programming techniques. We introduce the notion of effective new security and show that effectiveness restricts the no-arbitrage bid and ask prices of a new security to the interval defined by the minimum-cost problem. We discuss in detail the cases in which the boundaries of this interval can be reached without violating no-arbitrag
Distrubtion Tolerant Network Technology Flight Validation Report: DINET
No full textIn October and November of 2008, the Jet Propulsion Laboratory installed and tested essential elements of Delay/Disruption Tolerant Networking (DTN) technology on the Deep Impact spacecraft. This experiment, called Deep Impact Network Experiment (DINET), was performed in close cooperation with the EPOXI project which has responsibility for the spacecraft. During DINET some 300 images were transmitted from the JPL nodes to the spacecraft. Then, they were automatically forwarded from the spacecraft back to the JPL nodes, exercising DTN's bundle origination, transmission, acquisition, dynamic route computation, congestion control, prioritization, custody transfer, and automatic retransmission procedures, both on the spacecraft and on the ground, over a period of 27 days. All transmitted bundles were successfully received, without corruption. The DINET experiment demonstrated DTN readiness for operational use in space missions
Distribution Tolerant Network Technology Flight Validation Report: DINET
No full textIn October and November of 2008, the Jet Propulsion Laboratory installed and tested essential elements of Delay/Disruption Tolerant Networking (DTN) technology on the Deep Impact spacecraft. This experiment, called Deep Impact Network Experiment (DINET), was performed in close cooperation with the EPOXI project which has responsibility for the spacecraft. During DINET some 300 images were transmitted from the JPL nodes to the spacecraft. Then, they were automatically forwarded from the spacecraft back to the JPL nodes, exercising DTN's bundle origination, transmission, acquisition, dynamic route computation, congestion control, prioritization, custody transfer, and automatic retransmission procedures, both on the spacecraft and on the ground, over a period of 27 days. All transmitted bundles were successfully received, without corruption. The DINET experiment demonstrated DTN readiness for operational use in space missions
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