Gallium-nitride power transistor (GaN HEMT) and integrated circuit technologies have matured dramatically over the last few years, and many hundreds of thousands of devices have been manufactured and ...fielded in applications ranging from pulsed radars and counter-IED jammers to CATV modules and fourth-generation infrastructure base-stations. GaN HEMT devices, exhibiting high power densities coupled with high breakdown voltages, have opened up the possibilities for highly efficient power amplifiers (PAs) exploiting the principles of waveform engineered designs. This paper summarizes the unique advantages of GaN HEMTs compared to other power transistor technologies, with examples of where such features have been exploited. Since RF power densities of GaN HEMTs are many times higher than other technologies, much attention has also been given to thermal management-examples of both commercial "off-the-shelf" packaging as well as custom heat-sinks are described. The very desirable feature of having accurate large-signal models for both discrete transistors and monolithic microwave integrated circuit foundry are emphasized with a number of circuit design examples. GaN HEMT technology has been a major enabler for both very broadband high-PAs and very high-efficiency designs. This paper describes examples of broadband amplifiers, as well as several of the main areas of high-efficiency amplifier design-notably Class-D, Class-E, Class-F, and Class-J approaches, Doherty PAs, envelope-tracking techniques, and Chireix outphasing.
Record performance of high-power GaN/Al/sub 0.14/-Ga/sub 0.86/N high-electron mobility transistors (HEMTs) fabricated on semi-insulating (SI) 4H-SiC substrates is reported. Devices of 0.125-0.25 mm ...gate periphery show high CW power densities between 5.3 and 6.9 W/mm, with a typical power-added efficiency (PAE) of 35.4% and an associated gain of 9.2 dB at 10 GHz. High-electron mobility transistors with 1.5-mm gate widths (12×125 μm), measured on-wafer, exhibit a total output power of 3.9 W CW (2.6 W/mm) at 10 GHz with a PAE of 29% and an associated gain of 10 dB at the -2 dB compression point. A 3-mm HEMT, packaged with a hybrid matching circuit, demonstrated 9.1 W CW at 7.4 GHz with a PAE of 29.6% and a gain of 7.1 dB. These data represent the highest power density, total power, and associated gain demonstrated for a III-nitride HEMT under RF drive.
Very high power densities have been shown for both SiC MESFET and GaN HEMT devices. Both of these active devices benefit from the high breakdown voltages afforded by their wide-bandgap semiconductor ...properties. The GaN device also benefits from current densities as high as 1 A/mm. This high power density, along with good efficiency and linearity, provide an excellent base for future military and commercial power amplifier applications. High power densities are possible using narrow band power-matching networks. Although the gain-bandwidth limitation is exacerbated due to the high-impedance load lines required, high power design is possible even over multi-octave bandwidths.
SiC MESFET's have shown an RF power density of 4.6 W/mm at 3.5 GHz and a power added efficiency of 60% with 3 W/mm at 800 MHz, demonstrating that SiC devices are capable of very high power densities ...and high efficiencies. Single devices with 48 mm of gate periphery were mounted in a hybrid circuit and achieved a maximum RF power of 80 watts CW at 3.1 GHz with 38% PAE.
Platelet-activating factor (PAF) and structurally-related oxidized phospholipids are proinflammatory mediators in systemic inflammatory states such as severe sepsis. The enzyme platelet-activating ...factor acetylhydrolase (PAF-AH) rapidly degrades PAF and oxidized phospholipids into inactive metabolites. Reduced PAF-AH activity has been observed in patients with severe sepsis and may contribute to their systemic inflammatory response and organ dysfunction. A previous clinical trial with recombinant human PAF-AH (rPAF-AH, Pafase) suggested that this treatment may decrease 28-day all-cause mortality in patients with severe sepsis. The current study was undertaken to confirm this result.
A prospective, randomized, double-blind, placebo-controlled, multicenter, international trial.
One hundred forty-six intensive care units from nine countries.
Approximately 2,522 patients were planned to be enrolled < or =12 hrs after the onset of severe sepsis. Eligible patients were randomized to receive either rPAF-AH 1.0 mg/kg or placebo administered intravenously once daily for five consecutive days.
The study was terminated based on the recommendation of an independent data and safety monitoring committee after the second of three planned interim analyses, and the enrollment of 1,425 patients. rPAF-AH treatment was well tolerated among the 1,261 patients included in the interim analysis (643 rPAF-AH and 618 placebo), but did not decrease 28-day all-cause mortality compared with placebo (25% for rPAF-AH vs. 24% for placebo; relative risk, 1.03; 95% confidence interval, 0.85-1.25; p =.80). There were no statistically significant differences between treatment groups in any of the secondary efficacy end points. The overall incidence of adverse events was similar among rPAF-AH and placebo-treated patients, and no rPAF-AH-treated patients developed antibodies to PAF-AH.
rPAF-AH was well tolerated and not antigenic, but did not decrease 28-day all-cause mortality in patients with severe sepsis.
The genetic architecture of atrial fibrillation (AF) encompasses low impact, common genetic variants and high impact, rare variants. Here, we characterize a high impact AF-susceptibility allele, ...KCNQ1 R231H, and describe its transcontinental geographic distribution and history. Induced pluripotent stem cell-derived cardiomyocytes procured from risk allele carriers exhibit abbreviated action potential duration, consistent with a gain-of-function effect. Using identity-by-descent (IBD) networks, we estimate the broad- and fine-scale population ancestry of risk allele carriers and their relatives. Analysis of ancestral migration routes reveals ancestors who inhabited Denmark in the 1700s, migrated to the Northeastern United States in the early 1800s, and traveled across the Midwest to arrive in Utah in the late 1800s. IBD/coalescent-based allele dating analysis reveals a relatively recent origin of the AF risk allele (~5000 years). Thus, our approach broadens the scope of study for disease susceptibility alleles to the context of human migration and ancestral origins.
Background This Phase 4, open-label study evaluated the immunogenicity and safety of a second exposure to recombinant human thrombin (rThrombin) in adult patients with previous exposure to rThrombin. ...Study Design Topical rThrombin was applied as a hemostatic aid during a surgical procedure (day 1). Adverse events and clinical laboratory abnormalities were monitored to day 29 (study end). Immunogenicity samples were collected on days 1 and 29. Thirty-one patients were treated at 9 study sites; 30 patients completed the study. Results Mean age was 59.5 years; 61.3% of patients were male. Study operations types included spinal (n = 23 of 31; 74.2%), arterial reconstruction or peripheral arterial bypass (n = 4; 12.9%), arteriovenous vascular access procedure (n = 3; 9.7%), and other (n = 1; 3.2%). A median of 10 mL rThrombin (1,000 IU/mL; range 5 to 60 mL) was prepared per patient. Median elapsed time since previous rThrombin exposure was 1.3 years (range 19 days to 3.3 years). Recombinant human thrombin was not observed to be immunogenic; no patients (n = 0 of 30, 0%; 95% CI 0.0%, 11.6%) became positive for anti-rThrombin product antibodies at day 29, approximately 1 month after the second exposure to rThrombin. The most commonly reported adverse events were procedural pain (n = 23 of 31, 74.2%), constipation (n = 8, 25.8%), and nausea (n = 8, 25.8%) All adverse events and clinical laboratory abnormalities were considered unrelated to treatment. For the majority of patients, maximal severity of any adverse event was mild or moderate. Conclusions The immunogenicity and safety results of this Phase 4 rThrombin trial suggest that patients with known previous exposure may be safely re-exposed to topical rThrombin.
Background Immunoassays that detect antibovine thrombin product antibodies are not widely available. However, knowing whether these antibodies are present preoperatively would be useful because ...re-exposure to bovine thrombin-containing products is contraindicated in patients with pre-existing antiproduct antibodies due to the risk of developing immune-mediated coagulopathies. In these exploratory analyses, we characterized one aspect of immune sensitization, the persistence of circulating antibodies after exposure to bovine thrombin product. Study Design Elapsed time since a historical surgical procedure with documented or highly likely use of bovine thrombin product was determined for 204 patients enrolled in a recently completed trial. After study completion, baseline samples were assayed for antibovine thrombin product antibodies using validated immunoassays. Antibody data were sorted by time elapsed since the historical procedure. The proportion of patients with antibovine thrombin product antibodies and 95% confidence interval (CI) were determined for each 1-year period, providing an estimate for antibody persistence. Results Antibovine thrombin product antibodies were detected in 20.7% of patients (23 of 111; 95% CI 14.2%, 29.2%) with ≤1 year since the historical surgical procedure; 6.8% of patients (3 of 44; 95% CI 1.68%, 18.9%) with 1 to <2 years; 16.1% of patients (5 of 31; 95% CI 6.62%, 33.1%) with 2 to <3 years; and 5.6% of patients (1 of 18; 95% CI 0.00%, 27.6%) with ≥3 years since the historical procedure. Conclusions The proportion of patients with antibovine thrombin product antibodies ranged from 5.6% to 20.7% across the multiyear postoperative window. Clinicians should be aware that antibodies to bovine thrombin products may persist for years after exposure.
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