Early stopping by using stochastic curtailment in a three-arm sequential trial

Summary. Interim analysis is important in a large clinical trial for ethical and cost considerations. Sometimes, an interim analysis needs to be performed at an earlier than planned time point. In that case, methods using stochastic curtailment are useful in examining the data for early stopping while controlling the inflation of type I and type II errors. We consider a three-arm randomized study of treatments to reduce perioperative blood loss following major surgery. Owing to slow accrual, an unplanned interim analysis was required by the study team to determine whether the study should be continued. We distinguish two different cases: when all treatments are under direct comparison and when one of the treatments is a control. We used simulations to study the operating characteristics of five different stochastic curtailment methods. We also considered the influence of timing of the interim analyses on the type I error and power of the test. We found that the type I error and power between the different methods can be quite different. The analysis for the perioperative blood loss trial was carried out at approximately a quarter of the planned sample size. We found that there is little evidence that the active treatments are better than a placebo and recommended closure of the trial.

Antigenic determinants at the carboxy terminus of chicken egg white riboflavin carrier protein (RCP): Epitope mapping and antibody-mediated pregnancy curtailment in rodents

The epitopic core sequences recognized by three monoclonal antibodies raised to chicken riboflavin carrier protein (RCP) were mapped to the C-terminal tail-end of the protein using the pepscan method A 21-residue synthetic peptide corresponding to residues 200-219 of the protein and comprising the regions corresponding to the antibodies was synthesized. Administration of polyclonal antibodies specific to this peptide led to termination of early pregnancy in mice. Also, active immunization of rats with the peptide-purified protein derivative conjugate inhibited establishment of pregnancy. These results demonstrate the functional importance of the C-terminal 200-219 region of chicken RCP. Copyright (C) 1996 Elsevier Science Ltd.

Fuzzy Monte Carlo mathematical model for load curtailment minimization in transmission power systems

This paper presents a methodology which is based on statistical failure and repair data of the transmission power system components and uses fuzzyprobabilistic modeling for system component outage parameters. Using statistical records allows developing the fuzzy membership functions of system component outage parameters. The proposed hybrid method of fuzzy set and Monte Carlo simulation based on the fuzzy-probabilistic models allows catching both randomness and fuzziness of component outage parameters. A network contingency analysis to identify any overloading or voltage violation in the network is performed once obtained the system states by Monte Carlo simulation. This is followed by a remedial action algorithm, based on optimal power flow, to reschedule generations and alleviate constraint violations and, at the same time, to avoid any load curtailment, if possible, or, otherwise, to minimize the total load curtailment, for the states identified by the contingency analysis. In order to illustrate the application of the proposed methodology to a practical case, the paper will include a case study for the Reliability Test System (RTS) 1996 IEEE 24 BUS.

Voltage Analysis and Load Curtailment Minimization in Sub-transmission Networks with Distributed Generation

Most of distributed generation and smart grid research works are dedicated to network operation parameters studies, reliability, etc. However, many of these works normally uses traditional test systems, for instance, IEEE test systems. This paper proposes voltage magnitude and reliability studies in presence of fault conditions, considering realistic conditions found in countries like Brazil. The methodology considers a hybrid method of fuzzy set and Monte Carlo simulation based on the fuzzy-probabilistic models and a remedial action algorithm which is based on optimal power flow. To illustrate the application of the proposed method, the paper includes a case study that considers a real 12-bus sub-transmission network.

Stopping clinical trials because of treatment ineffectiveness: a comparison of a futility design with a method of stochastic curtailment

This paper introduces a simple futility design that allows a comparative clinical trial to be stopped due to lack of effect at any of a series of planned interim analyses. Stopping due to apparent benefit is not permitted. The design is for use when any positive claim should be based on the maximum sample size, for example to allow subgroup analyses or the evaluation of safety or secondary efficacy responses. A final frequentist analysis can be performed that is valid for the type of design employed. Here the design is described and its properties are presented. Its advantages and disadvantages relative to the use of stochastic curtailment are discussed. Copyright (C) 2003 John Wiley Sons, Ltd.

Chronic elevation of plasma thioredoxin: Inhibition of chemotaxis and curtailment of life expectancy in AIDS

Thioredoxin (Trx) is an intracellular redox protein with extracellular cytokine-like and chemokine-like activities. We show here that, although plasma Trx levels are unrelated to survival of HIV-infected individuals with CD4 cell counts above 200/μl blood, survival is significantly impaired (P = 0.003) when plasma Trx is chronically elevated in HIV-infected subjects with CD4 T cell counts below this level (i.e., with Centers for Disease Control (CDC)-defined AIDS). Relevant to the mechanism potentially underlying this finding, we also present data from experimental studies in mice showing that elevated plasma Trx efficiently blocks lipopolysaccharide (LPS)-induced chemotaxis, an innate immune mechanism that is particularly crucial when adaptive immunity is compromised. Thus, we propose that elevated plasma Trx in HIV-infected individuals with low CD4 T cell counts directly impairs survival by blocking pathogen-induced chemotaxis, effectively eliminating the last (innate) barrier against establishment of opportunistic and other infections in these immunodeficient individuals.

An analysis of wind curtailment and constraint at a nodal level

Many countries have set challenging wind power targets to achieve by 2020. This paper implements a realistic analysis of curtailment and constraint of wind energy at a nodal level using a unit commitment and economic dispatch model of the Irish Single Electricity Market in 2020. The key findings show that significant reduction in curtailment can be achieved when the system non-synchronous penetration limit increases from 65% to 75%. For the period analyzed, this results in a decreased total generation cost and a reduction in the dispatch-down of wind. However, some nodes experience significant dispatch-down of wind, which can be in the order of 40%. This work illustrates the importance of implementing analysis at a nodal level for the purpose of power system planning.

Baker Viewpoint: Curtailment Mortgages are a Win-Win Economic Policy

What happens if you prepay your standard residential mortgage? This question puzzles most people, and worse yet the answer can be even more confusing. However, a minor policy change that alters how prepayments are applied could benefit mortgage borrowers as well as the overall housing market.

A distributed control based coordination scheme of household PV systems for overvoltage prevention

This paper presents a distributed communication based active power curtailment (APC) control scheme for grid connected photovoltaic (PV) systems to address voltage rise. A simple distribution feeder model is presented and simulated using MATLAB. The resource sharing based control scheme proposed is shown to be effective at reducing voltage rise during times of peak generation and low load. Simulations also show the even distribution of APC using simple communications. Simulations demonstrate the versatility of the proposed control method under major communication failure conditions. Further research may lead to possible applications in coordinated electric vehicle (EV) charging.

Overvoltage and overloading prevention using coordinated PV inverters in distribution network

Overvoltage and overloading due to high utilization of PVs are the main power quality concerns for future distribution power systems. This paper proposes a distributed control coordination strategy to manage multiple PVs within a network to overcome these issues. PVs reactive power is used to deal with over-voltages and PVs active power curtailment are regulated to avoid overloading. The proposed control structure is used to share the required contribution fairly among PVs, in proportion to their ratings. This approach is examined on a practical distribution network with multiple PVs.

Genome-Wide Gene Expression Analysis Reveals a Dynamic Interplay between Luteotropic and Luteolytic Factors in the Regulation of Corpus Luteum Function in the Bonnet Monkey (Macaca radiata)

Although LH is essential for survival and function of the corpus luteum (CL) in higher primates, luteolysis occurs during nonfertile cycles without a discernible decrease in circulating LH levels. Using genome-wide expression analysis, several experiments were performed to examine the processes of luteolysis and rescue of luteal function in monkeys. Induced luteolysis with GnRH receptor antagonist (Cetrorelix) resulted in differential regulation of 3949 genes, whereas replacement with exogenous LH (Cetrorelix plus LH) led to regulation of 4434 genes (1563 down-regulation and 2871 up-regulation). A model system for prostaglandin (PG) F-2 alpha-induced luteolysis in the monkey was standardized and demonstrated that PGF(2 alpha) regulated expression of 2290 genes in the CL. Analysis of the LH-regulated luteal transcriptome revealed that 120 genes were regulated in an antagonistic fashion by PGF(2 alpha). Based on the microarray data, 25 genes were selected for validation by real-time RT-PCR analysis, and expression of these genes was also examined in the CL throughout the luteal phase and from monkeys treated with human chorionic gonadotropin (hCG) to mimic early pregnancy. The results indicated changes in expression of genes favorable to PGF(2 alpha) action during the late to very late luteal phase, and expressions of many of these genes were regulated in an opposite manner by exogenous hCG treatment. Collectively, the findings suggest that curtailment of expression of downstream LH-target genes possibly through PGF(2 alpha) action on the CL is among the mechanisms underlying cross talk between the luteotropic and luteolytic signaling pathways that result in the cessation of luteal function, but hCG is likely to abrogate the PGF(2 alpha)-responsive gene expression changes resulting in luteal rescue crucial for the maintenance of early pregnancy. (Endocrinology 150: 1473-1484, 2009)

Quantifying the value of improved wind energy forecasts in a pool-based electricity market

This work illustrates the influence of wind forecast errors on system costs, wind curtailment and generator dispatch in a system with high wind penetration. Realistic wind forecasts of different specified accuracy levels are created using an auto-regressive moving average model and these are then used in the creation of day-ahead unit commitment schedules. The schedules are generated for a model of the 2020 Irish electricity system with 33% wind penetration using both stochastic and deterministic approaches. Improvements in wind forecast accuracy are demonstrated to deliver: (i) clear savings in total system costs for deterministic and, to a lesser extent, stochastic scheduling; (ii) a decrease in the level of wind curtailment, with close agreement between stochastic and deterministic scheduling; and (iii) a decrease in the dispatch of open cycle gas turbine generation, evident with deterministic, and to a lesser extent, with stochastic scheduling.

Cost savings from relaxation of operational constraints on a power system with high wind penetration

Wind energy is predominantly a nonsynchronous generation source. Large-scale integration of wind generation with existing electricity systems, therefore, presents challenges in maintaining system frequency stability and local voltage stability. Transmission system operators have implemented system operational constraints (SOCs) in order to maintain stability with high wind generation, but imposition of these constraints results in higher operating costs. A mixed integer programming tool was used to simulate generator dispatch in order to assess the impact of various SOCs on generation costs. Interleaved day-ahead scheduling and real-time dispatch models were developed to allow accurate representation of forced outages and wind forecast errors, and were applied to the proposed Irish power system of 2020 with a wind penetration of 32%. Savings of at least 7.8% in generation costs and reductions in wind curtailment of 50% were identified when the most influential SOCs were relaxed. The results also illustrate the need to relax local SOCs together with the system-wide nonsynchronous penetration limit SOC, as savings from increasing the nonsynchronous limit beyond 70% were restricted without relaxation of local SOCs. The methodology and results allow for quantification of the costs of SOCs, allowing the optimal upgrade path for generation and transmission infrastructure to be determined.

Application of PMUs to Coordinate Hydroelectric and Wind Power Plant Operation

It is acknowledged that wind power is a stochastic energy source compared to hydroelectric generation which is easily scheduled. In this paper a scheme for coordinating wind power plant and hydroelectric power plant is presented by using PMUs to measure and control the state of wind and hydro power plants. Hydroelectric generation is proposed as a method of energy reserve and compensation in the context of wind power fluctuation in order to avoid full or partial curtailment of wind generation to benefit wind providers. The feasibility of this proposed scheme is investigated by power flow calculation and stability analysis using the IEEE 30-bus power system model.

Distribution Network Voltage Support Using Sensitivity-based Dispatch of Distributed Generation

This paper is concerned with the voltage and reactive power issues surrounding the connection of Distributed Generation (DG) on the low-voltage (LV) distribution network. The presented system-wide voltage control algorithm consists of three stages. Firstly available reactive power reserves are utilized. Then, if required, DG active power output is curtailed. Finally, curtailment of non-critical site demand is considered. The control methodology is tested on a variant of the 13-bus IEEE Node Radial Distribution Test Feeder. The presented control algorithm demonstrated that the distribution system operator (DSO) can maintain voltage levels within a desired statutory range by dispatching reactive power from DG or network devices. The practical application of the control strategy is discussed.