Steady-state Period Research Articles

Steady state adjusting trends using a data-driven local polynomial regression

Economic variables usually follow a dynamic trend pattern. However, it is difficult to estimate this trend precisely as numerous economically- and statistically-based estimation methods exist. This contribution proposes a data-driven nonparametric trend that is local polynomial, to improve arbitrary trend estimations of commonly used methods concerning the selection of the smoothing parameter and the dependence structure. An iterative plug-in (IPI) algorithm determines the bandwidth endogenously and allows a theory-based interpretation of the length of growth processes. This length of the bandwidth reflects the lengths of the steady state periods. Consequently, the bandwidth identifies the time period of stable economic conditions and can detect economic changes. To demonstrate the power of this estimation approach, an extensive simulation study is performed. Furthermore, examples using US and UK GDP data along with a guide for the optimal choice of algorithms for empirical applications are provided. This proposed method yields new insights for growth dynamics, cyclical movements and their dependence.

Time-Varying Model Predictive Control of a Reversible-SOC Energy-Storage Plant Based on the Linear Parameter-Varying Method

Hydrogen conversion plants based on reversible solid oxide cells (rSOCs) provide a potential solution for large-scale energy storage to facilitate renewable integration. When operating an rSOC plant, the security and performance should be monitored at all times, including the steady-state periods and the transient processes connecting them. Model predictive control (MPC) is an appropriate method for this problem. This paper presents a comprehensive rSOC plant model to describe the multiscale dynamics (such as temperature and mass flows) under both fuel cell and electrolysis modes. Then, a time-varying MPC strategy based on a linear parameter-varying prediction model is proposed to provide fast control to the nonlinear rSOC plant. A numerical case is simulated to validate the effects of the proposed MPC strategy. The results suggest that the automatic coordination of actuators ensures consistent stack security, improves both short-term tracking and long-term production performance, and ultimately benefits the plant economically in practical operation.

On the boundedness of running-in attractors based on recurrence plot and recurrence qualification analysis

A feature parameter was proposed to quantitatively explore the boundedness of running-in attractors; its variation throughout the friction process was also investigated. The enclosing radius R was built with recurrence plots (RPs) and recurrence qualification analysis (RQA) by using the time delay embedding and phase space reconstruction. Additionally, the typology of RPs and the recurrence rate (RR) were investigated to verify the applicability of R in characterizing the friction process. Results showed that R is larger at the beginning, but exhibits a downward trend in the running-in friction process; R becomes smooth and trends to small steady values during the steady-state friction period, and finally shows an upward trend until failure occurs. The evolution of R, which corresponded with the typology of RPs and RR during friction process, can be used to quantitatively analyze the variation of the running-in attractors and friction state identifacation. Hence, R is a valid parameter, and the boundedness of running-in attractors can offer a new way for monitoring the friction state of tribological pairs.

80,000 current on/off cycles in a one year long steam electrolysis test with a solid oxide cell

The current ON/OFF switching of a solid oxide electrolysis cell is treated as elementary step for power variation in a steam electrolyser system. If the cell voltage in the ON mode is adjusted to the thermal neutral voltage, heat generation remains zero in both modes, which largely facilitates the thermal management. To verify whether the cells withstand the switching, an electrolysis durability test with an electrolyte supported solid oxide cell was performed during one year at about 850 °C. The cell consisted of a 3YSZ electrolyte, CGO diffusion-barrier/adhesion layers, a lanthanum strontium cobaltite ferrite (LSCF) oxygen electrode, and a nickel/gadolinia-doped ceria (Ni/GDC) steam/hydrogen electrode. The test included two operation blocks with each 40,000 cycles of 2 min duration and a current density of −0.7 Acm−2 in the ON mode (−0.07 Acm−2 in OFF mode), as well as steady-state ON periods with 5800 h duration. Voltage degradation was 5 mV/1000 h (0.4%/1000 h) and the increase in the area specific resistance 7 mΩcm2/1000 h, without notable dependence on current cycling. Impedance spectroscopic results were in agreement with the only small switching transients seen in the cell voltage; moreover, they confirmed a dominating ohmic degradation together with minor contributions from gas conversion and reaction, respectively. No electrode delamination was detectable after scheduled test completion.

Importance of Species Sorting and Immigration on the Bacterial Assembly of Different-Sized Aggregates in a Full-Scale Aerobic Granular Sludge Plant.

In aerobic granular sludge (AGS) systems, different-sized microbial aggregates having different solids retention time (SRT) coexist in the same reactor compartment and are subjected to the same influent wastewater. Thus, the AGS system provides a unique ecosystem to study the importance of local (species sorting) and regional (immigration) processes in bacterial community assembly. The microbial communities of different-sized aggregates (flocs <0.2 mm, small granules (0.2-1.0 mm) and large granules >1.0 mm), influent wastewater, excess sludge and effluent of a full-scale AGS plant were characterized over a steady-state operation period of 6 months. Amplicon sequencing was integrated with mass balance to determine the SRT and net growth rate of operational taxonomic units (OTUs). We found strong evidence of species sorting as opposed to immigration, which was significantly higher at short SRT (i.e., flocs and small granules) than that at long SRT (large granules). Rare OTUs in wastewater belonging to putative functional groups responsible for nitrogen and phosphorus removal were progressively enriched with an increase in microbial aggregates size. In contrast, fecal- and sewage infrastructure-derived microbes progressively decreased in relative abundance with increase in microbial aggregate size. These findings highlight the importance of AGS as a unique model ecosystem to study fundamental microbial ecology concepts.

Thermodynamic properties of microorganisms: determination and analysis of enthalpy, entropy, and Gibbs free energy of biomass, cells and colonies of 32 microorganism species

Thermodynamic analysis is an important part of chemical engineering. However, its application in biotechnology has been hampered by lack of data on thermodynamic properties of microorganism biomass. In this paper, a review was made of methods for estimation of thermodynamic properties of biomass, including standard enthalpy of combustion hC⁰, enthalpy of formation hf⁰, entropy s⁰, and Gibbs free energy of formation gf⁰. These parameters were calculated on molar and mass specific basis for 32 microorganism species, including 14 bacteria, 7 yeast and 11 algae species. It was found that hf⁰, s⁰, gf⁰ are, respectively, similar for all the analyzed species, due to the fact that all living organisms have a common ancestor and thus a similar chemical composition. Furthermore, all the analyzed microorganisms have negative hf⁰, originating from partial oxidation of all other elements by oxygen and nitrogen. A brief review was given of microorganism endogenous and growth metabolic rates. Finally, based on the determined thermodynamic properties, entropy of individual E. coli and Pseudomonas cells were determined and entropy of a Pseudomonas colony during its lifespan was calculated and analyzed. Three periods can be distinguished in the existence of a microorganism colony: (a) accumulation period when cell number, mass and entropy increase, (b) steady state period when they are approximately constant, and (c) decumulation period when they decrease.

Methods for Estimating Resting Energy Expenditure Using Indirect Calorimetry in Adults with Overweight and Obesity (P13-030-19)

ObjectivesStandard procedures to estimate resting energy expenditure (REE) using indirect calorimetry are time-consuming, and may be unnecessary. Indeed, the guidelines recommend a pre-test resting period of 30-minutes, followed by a 5-minute stabilization period, and then waiting until the first steady state period (SS), defined as a 5-minute period with a coefficient of variance (CV) of <10% for VO2 and VCO2, to estimate REE. The aim of the study was to evaluate alternative procedures for estimating REE in adults with overweight and obesity. MethodsIndirect calorimetry was performed in 37 adults enrolled in a weight loss trial using a metabolic cart (Quark RMR, COSMED). The volume of oxygen (VO2) and volume of carbon dioxide (VCO2) were collected every 10 sec for ≥20-minutes following pre-test resting (10-mins) and stabilization (5-mins) periods. The measurement period was segmented into five-minute (REE6–10, REE11–15, REE16–20, and REE21–25) and rolling (REE6–15, REE6–20, and REE6–25) periods, and VO2, VCO2, and CV were calculated for each period. REE was calculated using standard criteria (REESS). Alternative SS periods of 3- and 4-minutes (REE3 and REE4) were applied to those who did not achieve REESS. REESS estimates were compared to the other estimates of REE using paired t-tests. ResultsParticipants were 51 ± 14SD yo, primarily women (78%), and had a BMI of 35.4 ± 5.5SD kg/m2. REESS was achieved by 81% (n = 30) of all participants, and 54% (n = 20) achieved REESS during the first 5-minute period (REE6–10) following stabilization. Applying REE3 and REE4 criteria, those who did not reach REESS increased to 92% (n = 34). There were no significant differences between REESS, and REE3 (P = 0.21), REE4 (P = 0.40), REE6–10 (P = 0.38), REE6–15 (P = 0.15) or REE6–20 (P = 0.05). ConclusionsThe majority of adults with overweight and obesity met the standard criteria for SS following a reduced pre-test resting period. However, the non-significant difference between REESS and rolling averages suggest the standard criteria may be unnecessary in a group setting. Funding SourcesAmerican Heart Association.

Validation Of Gas Analysis Over Incremental Work Intensities - A Comparison Of Two Metabolic Measurement Systems

Indirect calorimetry is a practical and accurate method of measuring metabolic gas exchange rate, specifically volume of oxygen and carbon dioxide (V̇O2 and V̇CO2). Commercial stationary and mobile systems typically include automated metabolic gas analyses. Metabolic cart systems are considered the standard; however, they pose limitations due to cost and portability. PURPOSE: To compare the accuracy of a commercially available mobile system (CareFusion Oxycon Mobile®, OXYCON) to a criterion stationary cart system (ParvoMedics TrueOne 2400®, PARVO). METHODS: Fifteen volunteers (13 Male, 2 Female; 24 ± 6 y (mean ± SD), 77 ± 13 kg BW, VO2peak 3.9 ± 0.7 L∙min-1) completed four trials over two non-consecutive study days. Trials consisted of a rest period, followed by three incremental treadmill work rates: walk (23-36% VO2peak), jog (49-67% VO2peak), and run (60-76% VO2peak) in controlled laboratory conditions (20 ± 0.5 °C; 45 ± 22 % RH). Metabolic system order was randomized and data collected was averaged over 3-4 minute steady-state periods from each work intensity. Correlation coefficients and systematic bias were used to evaluate the agreement between the systems. RESULTS: Measurements of V̇O2 from the OXYCON and PARVO were highly correlated (R2= 0.99). The OXYCON showed some positive bias (0.18 ± 0.16 L∙min-1) that increased with work intensity: rest (V̇O2 0.05 ± 0.06 L∙min-1), walk (V̇O2 0.15 ± 0.09 L∙min-1), jog (V̇O2 0.26 ± 0.16 L∙min-1), and run (V̇O2 0.31 ± 0.16 L∙min-1). CONCLUSION: The mobile OXYCON is an acceptable alternative to stationary metabolic cart systems for measuring metabolic gas exchange rate during rest and low intensity exercise. Clinicians may consider alternative devices for assessments at higher work intensities.

Validity of a New Portable Metabolic Gas Exchange System

Valid and reliable methods to measure oxygen consumption (V̇O2) and carbon dioxide production (V̇CO2) are required in the assessment of exercise capacity and energy expenditure. However, research is often restricted by financial and portability issues with existing open circuit spirometry, metabolic cart or portable devices. PURPOSE: Evaluate a new, light-weight and scalable metabolic system (CO2/O2 Breath & Respiration Analyzer, COBRA) against a criterion metabolic cart system (Parvomedics TrueOne 2400®, PARVO). METHODS: Fourteen volunteers (13 male, 1 female; 24 ± 6 y (mean ± SD), 76 ± 13 kg BW, VO2peak 3.8 ± 0.7 L∙min-1) performed four identical trials over two laboratory test days. The COBRA and PARVO were used to monitor four steady-state work rates: sitting rest, walk (23-36% VO2peak), jog (49-67% VO2peak), and run (60-76% VO2peak) on a treadmill in a laboratory (20 ± 0.5 °C; 45 ± 22 % RH). Simultaneous gas samples were averaged over 3-4 minute steady-state periods for each work intensity. Coefficient of determination and Concordance Correlation Coefficients (CCC) were used to evaluate the agreement between the systems when measuring V̇O2, V̇CO2, and minute ventilation (VE). Systematic bias was examined to assess the accuracy of the COBRA. RESULTS: The COBRA and PARVO produced highly correlated measures of V̇O2 (R2= 0.98), V̇CO2 (R2= 0.98) and VE (R2= 0.99). The COBRA had very low bias compared to the PARVO for V̇O2 (0.01 ± 0.13 L∙min-1), V̇CO2 (0.06 ± 0.13 L∙min-1), and VE (2.12 ± 2.75 L∙min-1). COBRA was in high agreement (CCC= 0.99) with the PARVO across each measure of V̇O2, V̇CO2 and VE. CONCLUSION: The COBRA device is an accurate mobile metabolic system for measuring respiratory variables across a range of work intensities. Disclaimer: The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government.

Dynamic sensor-balanced knee arthroplasty: can the sensor "train" the surgeon?

BackgroundDynamic tibial tray sensors are playing an increasing role in total knee arthroplasty (TKA) coronal balancing. Sensor balance is proposed to lead to improved patient outcomes compared with sensor-unbalanced TKA, and traditional manual-balanced TKA. However, the “learning curve” of this technology is not known, and also whether sensor use can improve manual TKA balance skills once the sensor is taken away, effectively “training” the surgeon.MethodsWe conducted a single-surgeon prospective study on 104 consecutive TKAs. In Nonblinded Phase I (n = 49), sensor-directed releases were performed during trialing and final intercompartmental load was recorded. In Blinded Phase II (n = 55), manual-balanced TKA was performed and final sensor readings were recorded by a blinded observer after cementation. We used cumulative summation analysis and sequential probability ratio testing to analyze the surgeon learning curve in both phases.ResultsIn Nonblinded Phase I, sensor balance proficiency was attained most easily at 10°, followed by 90°, and most difficult to attain at 45° of flexion. In Blinded Phase II, manual balance was lost most quickly at 45°, followed by 90°, and preserved for longest at 10° of flexion. The number of cases in the steady state periods (early phase periods where there is a mix of sensor balance and sensor imbalance) for both phases is similar.ConclusionsA surgeon who consistently uses the dynamic sensor demonstrates a learning curve with its use, and an “attrition” curve once it is removed. Consistent sensor balance is more predictable with constant sensor use.

Optimal integrated schedule of entire process of dual-blade multi-cluster tools from start-up to close-down

Multi-cluster tools are widely used in majority of wafer fabrication processes in semiconductor industry. Smaller lot production, thinner circuit width in wafers, larger wafer size, and maintenance have resulted in a large quantity of their start-up and close-down transient periods. Yet, most of existing efforts have been concentrated on scheduling their steady states. Different from such efforts, this work schedules their transient and steady-state periods subject to wafer residency constraints. It gives the schedulability conditions for the steady-state scheduling of dual-blade robotic multi-cluster tools and a corresponding algorithm for finding an optimal schedule. Based on the robot synchronization conditions, a linear program is proposed to figure out an optimal schedule for a start-up period, which ensures a tool to enter the desired optimal steady state. Another linear program is proposed to find an optimal schedule for a close-down period that evolves from the steady state period. Finally, industrial cases are presented to illustrate how the provided method outperforms the existing approach in terms of system throughput improvement.

Design and Experimental Verification of a High-Voltage Series-Stacked GaN eHEMT Module for Electric Vehicle Applications

A gallium nitride (GaN) power switching module with extended rated voltage is proposed for electric vehicle power conditioning system. Limited breakdown voltage of GaN high-electron-mobility transistors (HEMTs) hinders their usage in high-voltage applications. The presented GaN module is composed of two series-stacked enhancement-mode HEMTs for the purpose of duplicating the breakdown voltage. An integrated series-switch driver (SSD) is used to drive the stacked eHEMTs. The SSD provides adequate gate charge for both HEMTs in the module, and guarantees balanced voltage sharing between the devices during the switching transitions and steady state. The operation principle of the module is described thoroughly, and an analytical model has been derived considering parasitic inductances. Simulation analysis is carried out to study the performance of the SSD in various conditions. Also, the effect of variation in the SSD parameters on the gate–source voltage oscillation is investigated. Finally, an experimental setup of a bidirectional boost converter with two 1.3-kV GaN eHEMT modules is developed and tested under various scenarios. Moreover, a loss comparison between the proposed 1.3-kV GaN module and a 1.2-kV SiC MOSFET is carried out. The simulation and experimental results show that the developed GaN eHEMT module has satisfying dynamic and static performance with less than 10% voltage mismatch during the steady-state period for all scenarios. Also, the GaN module proved to have 35%–55% lower power loss (for different switching frequencies) compared to the SiC MOSFET counterpart.

EEG profiles during general anesthesia in children: A comparative study between sevoflurane and propofol.

In this prospective study, we describe the electroencephalographic (EEG) profiles in children anesthetized with sevoflurane or propofol. Seventy-three subjects (11years, range 5-18) were included and randomly assigned to two groups according to the anesthetic agent. Anesthesia was performed by target-controlled infusion of propofol (group P) or by sevoflurane inhalation (group S). Steady-state periods were performed at a fixed randomized concentration between 2, 3, 4, 5, and 6μg.ml-1 of propofol in group P and between 1, 2, 3, 4, and 5% of sevoflurane in group S. Remifentanil was continuously administered throughout the study. Clinical data, Bispectral Index (BIS), and raw EEG were continuously recorded. The relationship between BIS and anesthetic concentrations was studied using nonlinear regression. For all steady-state periods, EEG traces were reviewed to assess the presence of epileptoid signs, and spectral analysis of raw EEG was performed. Under propofol, BIS decreased monotonically and EEG slowed down as concentrations increased from 2 to 6μg.ml-1 . Under sevoflurane, BIS decreased from 0% to 4% and paradoxically rose from 4% to 5% of expired concentration: this increase in BIS was associated with the occurrence of fast oscillations and epileptoid signs on the EEG trace. Propofol was associated with more delta waves and burst suppression periods compared to sevoflurane. Under deep anesthesia, the BIS and electroencephalographic profiles differ between propofol and sevoflurane. For high concentrations of sevoflurane, an elevated BIS value may be interpreted as a sign of epileptoid patterns or EEG fast oscillations rather than an insufficient depth of hypnosis.

Performance‐recovery proportional‐type output‐voltage tracking algorithm of three‐phase inverter for uninterruptible power supply applications

This study suggests a proportional-type output-voltage control algorithm of a three-phase inverter for uninterruptible power supply applications with performance-recovery and offset-free properties. It makes the two contributions. The first one is to introduce first-order disturbance observers (DOBs) so as to exponentially estimate disturbances originating from model-plant mismatches. The second one is to rigorously prove that the proposed proportional-type feedback-linearising controller equipped with DOBs guarantees performance-recovery and offset-free properties. The experimental results conducted in this study, which uses a 10 kW three-phase inverter with an output capacitor, confirm that the closed-loop performance is satisfactory in both transient and steady-state periods.

Kinetic mechanism of Enterococcus faeciumd-aspartate ligase

Enterococcus faeciumd-aspartate ligase (Aslfm) is a peptide bond-forming enzyme that is involved in the peptidoglycan assembly pathway. It catalyzes the ATP-dependent ligation of the β-carboxylate of D-Asp to the ε-amino group of L-Lys in the nucleotide precursor UDP- MurNAc-pentapeptide. The enzyme is of interest as a target of new, potential, narrow-spectrum antibiotics directed against multiresistant E. faecium. The kinetic mechanism of Aslfm has not been fully characterized. To determine it, a progress curve analysis of Aslfm catalytic process using pyruvate kinase/lactate dehydrogenase ATPase detection assay was performed. With an inspection of the shape of measured progress curves and the results of specific qualitative experiments, the Aslfm reaction mechanism was singled out. The proposed Aslfm kinetics reaction scheme was evaluated by fitting the parameters of the corresponding differential equations to progress curves using the computer program ENZO. The complete kinetic analysis result is consistent with the substrate binding order 1) ATP, 2) D-Asp, and 3) UDP-MurNAc-pentapeptide. The analysis suggests that slowly establishing non-productive equilibria between the free and ATP-bound enzyme with the participating pentapeptide are responsible for initial reaction burst followed by a steady-state period before the complete depletion of the reactant added in the lowest concentration.

Sildenafil does not improve performance in 16.1 km cycle exercise time-trial in acute hypoxia.

Sildenafil is a pulmonary vasodilator that has potential to mitigate the decrement in endurance performance caused by hypoxic pulmonary vasoconstriction. The purpose of this study was to determine the effects of sildenafil on pulmonary artery pressure, cardiac output, pulse oxygen saturation, and exercise performance at moderate simulated altitude. We hypothesized that sildenafil would reduce the decline in exercise performance in hypoxia by blunting the rise in pulmonary artery pressure and causing a relative increase in cardiac output and oxygen saturation. Twelve endurance trained men performed three experimental cycling trials at sea level and simulated moderate altitude of 3,000m (FIO2 = 0.147) after ingesting either a placebo or sildenafil 50 mg capsule in a double blinded fashion. Each test consisted of a warmup period, a 15-minute steady state period at 60% of peak power output, and a 16.1 km time-trial. All subjects experienced a decline in maximal exercise capacity in hypoxia that ranged from 6% to 24%. This decline was correlated with the reduction in pulse oxygen saturation in hypoxic maximal exercise. Sildenafil had no effect on pulmonary artery pressure, cardiac output, or pulse oxygen saturation measured during steady state exercise. There was no effect of sildenafil on mean power output during the time-trial. During high intensity cycle exercise in acute, moderate hypoxia pulmonary artery pressure is unaffected by sildenafil and does not appear to influence cardiovascular function or exercise performance.

An analysis of premium payments as a mechanism for securing preferential service in cloud manufacturing

Paying a premium in a cloud manufacturing free market environment will benefit a customer during steady state scenarios, however during disruption this benefit diminishes to zero; dependent on the degree of disruption. These customers will recover quicker from disruptions, but the returns are small compared to the relative increase in cost. A cloud manufacturing scenario without contracts or preferential supply acts as a free market, this significantly increases supply chain risk. The predominant mechanism available to mitigate supply chain risk is the willingness to pay a premium. Agent-based simulation modelling experiments investigated this scenario using an extension of anarchic manufacturing for scheduling and control. The experiments induced a disruptive demand-side step change in requirement mix of capabilities and volume demanded by all customers. One customer was willing to pay a significant premium to the others. The waiting time (non-operating time) was analysed as the benefit and indicator for supply chain performance. The job cost for the customer willing to pay a premium relative to other customers and the relative waiting time were analysed during steady state, disruption, and recovery periods.

CARBON NANOMATERIAL PRODUCTION FROM PRODUCTS OF METHANE-AIR CONVERSION WITH SPENT GASES RECIRCULATION

The possibility of increasing of a specific yield of carbon nanomaterial from the products of methane-air conversion through the use of spent gases recirculation is considered. The analysis of the influence of water vapor and carbon dioxide contained in the recirculated gases on the methane conversion has been performed. According to the developed calculation method, the assessment of changes in the main parameters of carbon material synthesis was done. Evaluation was performed depending on the degree of recirculation of spent gases in the transition and steady-state periods of the process. It is shown that the use of gas recirculation increases the specific yield of the carbon material, but in this case, due to the accumulation of nitrogen in the gas phase, there is a decrease in the productivity of the process for the resulting product. The evaluation of the productivity enhancing by rising of the gases pressure in the system was made. It has been established that in order to increase the specific yield of carbon material, the obtained converted gas and reusable recirculated gas should be subjected to deep purification from water vapor. Bibl. 16, Fig. 6, Tab. 2.

Influence of epoxy resin on the microstructure and cavitation erosion of as-sprayed 8YSZ coating

The microstructures of materials are sensitive to shock waves and microjets induced by bubble collapse. The microstructure of coatings is thus closely related to their cavitation performance. Coating defects always act as the preferential sites for the bubble growth; thus, the materials around pores have been spalled preferentially under strong impact. In this study, epoxy resin (ER) was introduced into as-sprayed 8 wt% yttria-stabilized zirconia (8YSZ) coating by vacuum impregnation to prepare 8YSZ-ER coating. Results showed that the hardness, toughness, cohesive strength, and density of 8YSZ-ER coating are greatly improved. Cavitation performance is also improved; 8YSZ coating exhibited only a deceleration period whereas 8YSZ-ER coating showed a long steady-state period. This finding was mainly attributed to the enhanced compactness and cohesive strength of 8YSZ-ER coating, which caused the impact force to be evenly distributed on the specimen surface without accumulating in the pores. Cracks were also deflected, turned and terminated due to the presence of ER. Moreover, the relationship between ER aging and the damage mechanism of 8YSZ-ER coating under cavitation erosion was also examined.

LANADELUMAB 300MG EVERY 2 WEEKS EFFECTIVELY PREVENTED HEREDITARY ANGIOEDEMA ATTACKS IN THE HELP STUDY

Introduction Lanadelumab, a highly specific, fully human monoclonal antibody targeting plasma kallikrein, demonstrated sustained and well-tolerated prophylaxis against hereditary angioedema (HAE) attacks in the phase 3 HELP Study (NCT02586805). Three dosing regimens were investigated; here we report further efficacy findings for lanadelumab 300mg every 2 weeks (q2wks). Methods Patients with HAE type I/II, aged ≥12 years, and with ≥1 attack/month at baseline were randomized 2:2:2:3 to lanadelumab 150mg every 4 weeks (q4wks), 300mg q4wks, 300mg q2wks, or placebo. The primary endpoint was the number of investigator-confirmed attacks over the 26-week treatment period (days 0–182). Exploratory analyses included efficacy and AE-QoL during treatment period and steady state (days 70–182; 16 weeks). Results Overall, 125 patients were treated, of which 27 received lanadelumab 300mg q2wks and 41 received placebo. Demographics and baseline characteristics for the lanadelumab 300mg q2wks group were comparable with the placebo group: mean (SD) age 40.3 (13.4) years, 55.6% female, 51.9% experienced ≥3 attacks/month. Compared with placebo, treatment with lanadelumab 300mg q2wks significantly reduced mean attack rate and resulted in greater proportions of attack-free patients during days 0–182 and days 70–182 (Table). Meaningful improvement in AE-QoL score was 7.2 times more likely with lanadelumab 300mg q2wks than with placebo. Table. Efficacy outcomes with lanadelumab 300mg q2wks versus placebo in the overall treatment period and the steady-state period Conclusions Treatment with lanadelumab 300mg q2wks provided significant, clinically meaningful benefits to HAE patients during the 26-week treatment period, and particularly during the steady-state period, with 91.5% attack reduction versus placebo, 76.9% attack-free (versus 2.7% with placebo), and 92.5% reduction in rescue medication use versus placebo.