Desired Target Level Research Articles

Development and validation of intelligent load control for VRF air-conditioning system with deep learning based load forecasting

Variable refrigerant flow (VRF) air-conditioning systems have seen significant growth in Asia and its application is expanding globally. Despite the expanded application, most previous studies have focused on developing fault detection and diagnostics to achieve energy-efficient operations than on predicting power consumption. It's very difficult to predict the electrical consumption owing to its complex system configuration and various control strategies. A new control strategy is described for optimal adjustment of the desired target level based on time series forecasting using the optimized sequence to sequence model for VRF systems. Sequence to sequence (seq2seq) model with attention mechanism and Bayesian optimization is developed to predict accurate hourly and daily forecasts and rapid feedback control for fluctuating power consumption for VRF systems. The optimized seq2seq model is integrated into the intelligent load control (ILC). ILC can be used to manage VRF systems by dynamically prioritizing indoor units for curtailment using both quantitative inputs and qualitative rules. Overall, the results demonstrate that the deep learning based control allows coordination of the controllable loads of VRF systems in three commercial buildings. ILC with deep learning manages the power consumption within a desired target level, as well as indoor temperature reflecting the status of controlled indoor units, as objective functions of the control algorithm.

Audit Sistem Informasi Aplikasi Fingerspot Wdv 204bnc di Sekolah Islam Menggunakan Cobit 5

This research was conducted to identify and ensure that existing system procedures in the company function properly, using the Cobit 5 framework to audit the Fingerspot WDV 204BNC application information system in Islamic Schools using COBIT 5 with DSS03 and MEA01 domains and a comprehensive audit of the information system has never been carried out. used by the company so that the information system operational services cannot be ascertained whether or not they are by the school's standard needs. The information system audit on the Fingerspot WDV 204BNC application system running which is expected to run well according to the school's needs and objectives, with capability analysis. The audit results with the highest scores, namely the DSS03 domain, received a maturity level score of 8.55, and MEA 01 received a maturity level score of 13.91, with a Fully Achieved achievement score, all target levels have entered level 5 and the overall total maturity index score is 112.29 and maturity level is 22. .46, the average maturity index value is 56.15, while the capability maturity level is 11.23. From the results of the GAP analysis obtained from DSS03 and MEA01, it has reached the desired target level must be maintained, and must be improved further.

A Bayesian approach to pilot-pivotal trials for bioequivalence assessment

BackgroundTo demonstrate bioequivalence between two drug formulations, a pilot trial is often conducted prior to a pivotal trial to assess feasibility and gain preliminary information about the treatment effect. Due to the limited sample size, it is not recommended to perform significance tests at the conventional 5% level using pilot data to determine if a pivotal trial should take place. Whilst some authors suggest to relax the significance level, a Bayesian framework provides an alternative for informing the decision-making. Moreover, a Bayesian approach also readily permits possible incorporation of pilot data in priors for the parameters that underpin the pivotal trial.MethodsWe consider two-sequence, two-period crossover designs that compare test (T) and reference (R) treatments. We propose a robust Bayesian hierarchical model, embedded with a scaling factor, to elicit a Go/No-Go decision using predictive probabilities. Following a Go decision, the final analysis to formally establish bioequivalence can leverage both the pilot and pivotal trial data jointly. A simulation study is performed to evaluate trial operating characteristics.ResultsCompared with conventional procedures, our proposed method improves the decision-making to correctly allocate a Go decision in scenarios of bioequivalence. By choosing an appropriate threshold, the probability of correctly (incorrectly) making a No-Go (Go) decision can be ensured at a desired target level. Using both pilot and pivotal trial data in the final analysis can result in a higher chance of declaring bioequivalence. The false positive rate can be maintained in situations when T and R are not bioequivalent.ConclusionsThe proposed methodology is novel and effective in different stages of bioequivalence assessment. It can greatly enhance the decision-making process in bioequivalence trials, particularly in situations with a small sample size.

Seismic retrofit of reinforced concrete frames by direct loss-based design

This paper introduces a procedure for the retrofit design of reinforced concrete (RC) frame buildings to achieve the desired target level of earthquake-induced loss for a given seismic hazard profile. The methodology is “direct” because the loss target is specified in the first step of the procedure, and, in principle, no design iterations are required. The target loss level is defined based on designer/client preferences and/or external constraints (e.g., foundation capacity). The proposed procedure relies on a simplified loss assessment enabled by a surrogate model defining the probability distribution of the seismic deformation demands of single degree of freedom (SDoF) systems given different ground-motion intensity levels. Combined with a hazard curve and a building-level damage-to-loss model, such a surrogate model is used to map candidate SDoF force-displacement curves to their earthquake-induced loss by assuming a given retrofit strategy. In this case, the considered retrofit strategy involves changing the frame's local hierarchy of strength to ensure a global plastic structure mechanism. Under such assumptions, a designer can select a design force-displacement curve among those that comply with the chosen loss target. The detailing of the retrofitted frame is carried out according to the direct displacement-based design principles and the Simplified Lateral Mechanism Analysis (SLaMA). The procedure is applied to an under-designed RC frame building retrofitted with concrete jacketing. A benchmark loss estimate is calculated using non-linear time-history analyses for loss assessment purposes. The proposed procedure shows satisfactory compliance with the benchmark loss, emphasising the procedure's effectiveness in practice.

Use of agricultural production waste in relation to bio nano technology for the synthesis of functionalized selenium nanoparticles

The application of nanotechnological innovations to increase the effectiveness of the bioflavonoid quercetin is considered. The ability to functionalize with specific ligands that target specific organs or cells is very important because it is possible to increase the concentration of quercetin at the desired target level while reducing side effects. Quercetin, as a flavonoid antioxidant, is widely used to reduce oxidative stress and activate important signalling pathways in cells. However, poor solubility in water, intensive first-pass metabolism limits its use. A strategy for the development of nanocomposites is presented, which involves combining quercetin obtained from agricultural waste with selenium nanoparticles. In vitro results demonstrated that quercetin-nanoselenium has high water solubility compared to individual flavonoids. It has been proven that quercetin-nano-selenium nanoparticles are capable of reducing 1,1-dipheny l-2-picrylhydrazyl (DPPH) radicals and are characterized by high antioxidant activity. The ability to functionalize nanoparticles with specific ligands that target the modulation of specific signaling pathways (Keap1/ Nrf2/ARE, Nf-kB, mTOR) in individual cells is very important, as it allows increasing the concentration of quercetin to the desired level while reducing side effects. Considering the beneficial effects of quercetin, a strategy has been developed that involves the use of selenium nanoparticles to deliver quercetin in a specific and controlled manner. Research in this direction is promising, as it will contribute to clarifying the expediency of using such nanosystems, which have not yet been widely used. The use of onion waste and its extracts in biotechnology, biomedicine, pharmaceuticals and the agro-industrial sector can be an optimal solution for reducing environmental damage. In addition, it will provide an economically determined alternative for the production of feed additives for animals and poultry. Compounds of quercetin with nanoselenium should take a worthy place in clinical medical practice, biology and agriculture. The beneficial effects of quercetin can be further enhanced with the help of nanotechnology, which will contribute to the effective use of this compound with such great biological potential. Key words: nanobiotechnologies, waste, onion peel, 1,1-dipheny l- 2-picrylhydrazyl, antiradical activity.

Analytical Investigation and Heuristic Optimization of Surface Mounted Permanent Magnet Machines With Hybrid Magnetic Structure

Cogging torque causes major operational setbacks for Permanent Magnet (PM) machine operation, particularly in applications where a quiet performance is desired. This paper presents a heuristic optimization framework to optimize the cogging torque in Surface Mounted Permanent Magnet (SPM) machines consisting of a hybrid magnetic structure (i.e., rare-earth and ferrite magnets). To avoid excessive computational time and volume associated with Finite Element (FE)-based optimization solutions, analytical approach is paired up with the optimization algorithm to determine the optimal design while FE is utilized for verification and validation purposes. First, analytical expressions are established for individual objective functions (i.e., airgap PM flux distribution, and cogging torque), and their corresponding spatial harmonics are identified using the air-gap field modulation theory. Next, the presented analytical model is utilized to optimize the system (i.e., minimize the cogging torque) to the desired target level via two different solutions (i.e., Genetic Algorithm (GA) and Particle Swarm Optimization (PSO)), and their respective performance are compared. To determine the efficacy of the presented solutions, the optimal hybrid machine response is compared against the baseline structure.

On the Role of the Excitation/Inhibition Balance of Homeostatic Artificial Neural Networks.

Homeostatic models of artificial neural networks have been developed to explain the self-organization of a stable dynamical connectivity between the neurons of the net. These models are typically two-population models, with excitatory and inhibitory cells. In these models, connectivity is a means to regulate cell activity, and in consequence, intracellular calcium levels towards a desired target level. The excitation/inhibition (E/I) balance is usually set to 80:20, a value characteristic for cortical cell distributions. We study the behavior of these homeostatic models outside of the physiological range of the E/I balance, and we find a pronounced bifurcation at about the physiological value of this balance. Lower inhibition values lead to sparsely connected networks. At a certain threshold value, the neurons develop a reasonably connected network that can fulfill the homeostasis criteria in a stable way. Beyond the threshold, the behavior of the artificial neural network changes drastically, with failing homeostasis and in consequence with an exploding number of connections. While the exact value of the balance at the bifurcation point is subject to the parameters of the model, the existence of this bifurcation might explain the stability of a certain E/I balance across a wide range of biological neural networks. Assuming that this class of models describes the self-organization of biological network connectivity reasonably realistically, the omnipresent physiological balance might represent a case of self-organized criticality in order to obtain a good connectivity while allowing for a stable intracellular calcium homeostasis.

Experimental Design for the Lifetime Performance Index of Weibull Products Based on the Progressive Type I Interval Censored Sample

In this study, the experimental design is developed based on the testing procedure for the lifetime performance index of products following Weibull lifetime distribution under progressive type I interval censoring. This research topic is related to asymmetrical probability distributions and applications across disciplines. The asymptotic distribution of the maximum likelihood estimator of the lifetime performance index is utilized to develop the testing procedure. In order to reach the given power level, the minimum sample size is determined and tabulated. In order to minimize the total cost that occurred under progressive type I interval censoring, the sampling design is investigated to determine the minimum number of inspection intervals and equal interval lengths when the termination time of experiment is fixed or not fixed. For illustrative aims, one practical example is given for the implementation of our proposed sampling design to collect the progressive type I interval censored sample so that the users can use this sample to test if the lifetime performance index exceeds the desired target level.

Oxidative Stress in Neutrophils: Implications for Diabetic Cardiovascular Complications.

Significance: Neutrophil behavior and function are altered by hyperglycemia associated with diabetes. Aberrant activation by hyperglycemia causes neutrophils to respond with increased production of reactive oxidative species (ROS). Excess ROS, a signature of primed neutrophils, can intracellularly induce neutrophils to undergo NETosis, flooding surrounding tissues with ROS and damage-associated molecular patterns such as S100 calcium binding proteins (S100A8/A9). The cargo associated with NETosis also attracts more immune cells to the site and signals for increased immune cell production. This inflammatory response to diabetes can accelerate other associated conditions such as atherosclerosis and thrombosis, increasing the risk of cardiovascular disease. Recent Advances: As the prevalence of diabetes continues to grow, more attention has been focused on developing effective treatment options. Currently, glucose-lowering medications and insulin injections are the most widely utilized treatments. As the disease progresses, medications are usually stacked to maintain glucose at desired target levels, but this approach often fails and does not effectively reduce cardiovascular risk, even with the latest drugs. Critical Issues: Despite advances in treatment options, diabetes remains a progressive disease as glucose lowering alone has failed to abolish the associated cardiovascular complications. Future Directions: Significant interest is being generated in developing treatments that do not solely focus on glucose control but rather mitigate glucotoxicity. Several therapies have been proposed that target cellular dysfunction downstream of hyperglycemia, such as using antioxidants to scavenge ROS, inhibiting ROS production from NOX, and suppressing neutrophil release of S100A8/A9 proteins. Antioxid. Redox Signal. 36, 652-666.

Individualized Prophylaxis with BAY 81-8973: Clinical Experience in an Italian Patient with Severe Hemophilia A

Introduction: Prophylaxis with a factor VIII (FVIII) product is the standard of care for patients with severe hemophilia A to prevent bleeding episodes and development of target joints and hemophilic arthropathy. In patients with established joint disease, prophylaxis can slow progression of joint damage, which can improve health-related quality of life. Adherence to prophylaxis is critical to its success. Missing or skipping a prophylaxis infusion can cause FVIII levels to fall below the desired target level, which can increase the risk of breakthrough bleeding episodes. To promote adherence to prophylaxis, healthcare providers and patients must work together to ensure that the prophylaxis regimen is manageable for each patient. In this case report, we describe the strategy we used to improve adherence, including changes to the prophylaxis dosing regimen, in a patient with severe hemophilia A.Demographics and medical history: A 54-year-old patient was diagnosed with severe hemophilia A in early childhood and treated on demand with a plasma-derived FVIII product, despite meeting criteria for use of prophylaxis. In 2000, he began tertiary prophylaxis with a standard-acting recombinant FVIII (rFVIII) product given twice weekly. At that time, he had target joints in both knees and both elbows and a Hemophilia Joint Health Score (HJHS) of 16. In 2007, he underwent surgical replacement of the left knee. In 2010, prophylaxis with a rFVIII was started at 3000 IU (32 IU/kg) 3 times per week. The patient's job as a vendor in outdoor markets affected his ability to adhere to this prophylaxis regimen. To facilitate adherence, prophylaxis dosing was decreased to twice weekly. The patient's comorbidities included obesity and hepatitis C infection, which did not respond to combined treatment with interferon and ribavirin.Current prophylaxis treatment: In 2015, because of weight gain (to 110 kg), joint bleeding episodes (2-3 per year), repeated occurrence of left ankle pain, and further joint deterioration (HJHS score, 25), prophylaxis dosing was increased to 4000 IU (40 IU/kg) 3 times per week. Adherence to this regimen was again difficult for the patient. In March 2017, based on pharmacokinetic results obtained in this patient with BAY 81-8973 (Kovaltry®, Bayer, Berkeley, CA; Table 1), he was transitioned to BAY 81-8973 5000 IU (45 IU/kg) twice weekly (every 84 hours, on Monday morning and Wednesday evening). This prophylaxis regimen accommodated his work schedule, and no bleeding episodes occurred after the patient started BAY 81-8973 prophylaxis.Conclusion: This case illustrates that the prophylaxis dose and dosing interval can be individually tailored, keeping in mind the clinical goal of treatment and the patient's bleeding phenotype and daily activities. In this patient, tailored prophylaxis dosing with BAY 81-8973 was key to improved adherence, outcomes, and health-related quality of life. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Drivers of farm business capital structure and its speed of adjustment: evidence from Western Australia’s Wheatbelt

The viability and profitability of a farm business can be influenced by how it chooses to fund its operations and capital investments either using debt or internal funds. This study examines the determinants and speed of adjustment of the capital structure of broadacre farm businesses in Western Australia’s Wheatbelt. Results show that prior period cash flow and equity, farm size and farm location are significant determinants of observed capital structures. Farm businesses are found to quickly adjust their capital structure to desired target levels, suggesting that adjustment costs are not high. The findings support the view that there is a pecking order in the choice of how farm businesses fund working capital and capital investments.

Self-Tuning Deep Brain Stimulation Controller for Suppression of Beta Oscillations: Analytical Derivation and Numerical Validation.

Closed-loop control strategies for deep brain stimulation (DBS) in Parkinson's disease offer the potential to provide more effective control of patient symptoms and fewer side effects than continuous stimulation, while reducing battery consumption. Most of the closed-loop methods proposed and tested to-date rely on controller parameters, such as controller gains, that remain constant over time. While the controller may operate effectively close to the operating point for which it is set, providing benefits when compared to conventional open-loop DBS, it may perform sub-optimally if the operating conditions evolve. Such changes may result from, for example, diurnal variation in symptoms, disease progression or changes in the properties of the electrode-tissue interface. In contrast, an adaptive or “self-tuning” control mechanism has the potential to accommodate slowly varying changes in system properties over a period of days, months, or years. Such an adaptive mechanism would automatically adjust the controller parameters to maintain the desired performance while limiting side effects, despite changes in the system operating point. In this paper, two neural modeling approaches are utilized to derive and test an adaptive control scheme for closed-loop DBS, whereby the gain of a feedback controller is continuously adjusted to sustain suppression of pathological beta-band oscillatory activity at a desired target level. First, the controller is derived based on a simplified firing-rate model of the reciprocally connected subthalamic nucleus (STN) and globus pallidus (GPe). Its efficacy is shown both when pathological oscillations are generated endogenously within the STN-GPe network and when they arise in response to exogenous cortical STN inputs. To account for more realistic biological features, the control scheme is then tested in a physiologically detailed model of the cortical basal ganglia network, comprised of individual conductance-based spiking neurons, and simulates the coupled DBS electric field and STN local field potential. Compared to proportional feedback methods without gain adaptation, the proposed adaptive controller was able to suppress beta-band oscillations with less power consumption, even as the properties of the controlled system evolve over time due to alterations in the target for beta suppression, beta fluctuations and variations in the electrode impedance.

Novel Approaches for Dietary Phosphorus Management in Chronic Kidney Disease

<p>Conventional approaches to alleviating hyperphosphatemia in patients with Chronic Kidney Disease (CKD) include dietary phosphorus restriction and use of phosphate binders. These approaches are, however not enough to control hyperphosphatemia and hence the need for novel nutritional approaches arises. Dietary phosphorus, protein and phytate values of some common food ingredients were obtained. Phosphates to protein ratio and net phosphorus absorption from the gut were reported on the basis of the phytate content of these ingredients. Among some common Indian food ingredients, phosphate to protein ratio was high in cereals, millets and dairy products. However due to presence of high amount of phytate, the net absorption of phosphate was lower from plant based sources of phosphorus as compared to animal based sources. It can be concluded that phosphorus to protein ratio is a metric which helps to ensure dietary phosphorus restriction with sufficient intake of proteins. Tables providing phosphorus to protein ratio along with phytate and per cent absorption may prove to be beneficial in achieving desired target levels of phosphorus for renal dieticians in case of CKD patients with hyperphosphatemia.</p>

Instant performance verification after electrochemical chloride extraction by enhanced corrosion testing

Electrochemical chloride extraction (ECE) is meant to re-establish the corrosion protection of concrete for the embedded reinforcement by removing chloride non-destructively and by enhancing the alkalinity of the rebar surrounding concrete. Both effects depend on various parameters, such as concrete cover, rebar spacing, chloride profile (especially if chloride ingress is deeper than the outside rebar layer) and concrete permeability. Often these parameters require long or multi-stage treatments, which basically can achieve any desired target level of chloride profile and impressed charge, but become a costly solution after a while. The acceptance criteria mentioned in CEN TS 14038-2 clause 8.6 refer to the achieved chloride content and to the amount of impressed charge, which are the conventional, easy measurable, but not direct parameters for evaluating the corrosion activity. A third parameter – the re-measurement of potentials for assessing (intended) low potential gradients and more positive average potentials – requires some weeks to months of depolarization and evaporation of water, before such a measurement can be applied successfully. A promising approach for an instant performance testing after an ECE treatment has been made on several occasions with follow-up measurements of electrolyte resistance, polarization resistance and corrosion current. Convincing changes towards significantly lower corrosion activity could be obtained (and compared to known classified values) – regardless of sometimes high residual chloride and very wet concrete. These data could be verified when re-assessed after some weeks, so enhanced corrosion measurements seem to be a useful tool for either establishing that the designed treatment time has been sufficient or to check on possible earlier termination of the treatment during a running ECE.

Personalized Prophylaxis in Hemophilia a: A Pediatric Center Experience in Mexico

Summary. Prophylaxis is the current standard of care for Hemophilia patients. However, the regimen should be individualized as much as possible based on age, bleeding phenotype and physical activity. PK based regimens have been proposed as an effective way to achieve more successful outcomes. According to 2016 WFH data, Mexico has 1.425 IU/capita mean use, which barely overcomes the limit of 1IU/ minimum target to achieve survival of the hemophilia population (WFH Report on the Annual Global Survey). Objectives. To examine a Mexican Center experience obtaining limited sampling PK profiles in pediatric patients. To determine the difference in frequency dosification in standard prophylaxis vs PK guided. Methods. Limited sampling was done in 14 pediatric patients with Hemophilia A without inhibitors, moderate to severe, in prophylaxis aged 2 to 14 years old using population PK tool myPKFiT. PK profiles based on the same data points plus patient characteristics were generated by a Bayesian algorithm with myPKFiT. Results. The mean age was 5.5 years (range 1-14 years) with a mean standard dose of 35 IU/k 2 times a week. The PK based mean dose was 27IU/kg 4 times a week. The mean half-life was 9.5 hours (range 6.8-11.6 hours. Conclusions. Shorter half life should be expected in pediatric patients, and be taken into account with other variables to achieve a personalized prophylaxis. Tailored prophylaxis facilitate patient education and adherence. Pediatric PK suggest shorter intervals or higher dosing are needed to achieve a desired target level. Use of myPKFiT and clinical, radiological and adherence scores to improve outcomes, in particular in the pediatric population. Integrating PK data into routine hemophilia care could provide promising results in developing countries. DisclosuresNo relevant conflicts of interest to declare.

Optimal Design of a Two-Stage Membrane System for Hydrogen Separation in Refining Processes

This paper fits into the process system engineering field by addressing the optimization of a two-stage membrane system for H2 separation in refinery processes. To this end, a nonlinear mathematical programming (NLP) model is developed to simultaneously optimize the size of each membrane stage (membrane area, heat transfer area, and installed power for compressors and vacuum pumps) and operating conditions (flow rates, pressures, temperatures, and compositions) to achieve desired target levels of H2 product purity and H2 recovery at a minimum total annual cost. Optimal configuration and process design are obtained from a model which embeds different operating modes and process configurations. For instance, the following candidate ways to create the driving force across the membrane are embedded: (a) compression of both feed and/or permeate streams, or (b) vacuum application in permeate streams, or (c) a combination of (a) and (b). In addition, the potential selection of an expansion turbine to recover energy from the retentate stream (energy recovery system) is also embedded. For a H2 product purity of 0.90 and H2 recovery of 90%, a minimum total annual cost of 1.764 M$·year−1 was obtained for treating 100 kmol·h−1 with 0.18, 0.16, 0.62, and 0.04 mole fraction of H2, CO, N2, CO2, respectively. The optimal solution selected a combination of compression and vacuum to create the driving force and removed the expansion turbine. Afterwards, this optimal solution was compared in terms of costs, process-unit sizes, and operating conditions to the following two sub-optimal solutions: (i) no vacuum in permeate stream is applied, and (ii) the expansion turbine is included into the process. The comparison showed that the latter (ii) has the highest total annual cost (TAC) value, which is around 7% higher than the former (i) and 24% higher than the found optimal solution. Finally, a sensitivity analysis to investigate the influence of the desired H2 product purity and H2 recovery is presented. Opposite cost-based trade-offs between total membrane area and total electric power were observed with the variations of these two model parameters. This paper contributes a valuable decision-support tool in the process system engineering field for designing, simulating, and optimizing membrane-based systems for H2 separation in a particular industrial case; and the presented optimization results provide useful guidelines to assist in selecting the optimal configuration and operating mode.

Integrated multi‐type sensor placement and response reconstruction method for high‐rise buildings under unknown seismic loading

SummaryStructural health monitoring system has been implemented on high‐rise buildings to provide real‐time measurement of structural responses for evaluating their serviceability, safety, and sustainability. However, because of the complex structural configuration of a high‐rise building and the limited number of sensors installed in the building, the complete evaluation of structural performance of the building in terms of the information directly recorded by a structural health monitoring system is almost impossible. This is particularly true when seismic‐induced ground motion is unknown. This paper thus proposes an integrated method that enables the optimal placement of multi‐type sensors on a high‐rise building on one hand and the reconstruction of structural responses and excitations using the information from the optimally located sensors on the other hand. The structural responses measured from multi‐type sensors are fused to estimate the full state of the building in the modal coordinates using Kalman filters, from which the structural responses at unmeasured locations and the seismic‐induced ground motion can be reconstructed. The optimal multi‐type sensor placement is simultaneously achieved by minimizing the overall estimation errors of structural responses at the locations of interest to a desired target level. A numerical study using a simplified finite element model of a high‐rise building is performed to illustrate the effectiveness and accuracy of the proposed method. The numerical results show that by using 3 types of sensors (inclinometers, Global Positioning System, and accelerometers), the proposed method offers an effective way to design a multi‐type sensor system, and the multi‐type sensors at their optimal locations can produce sufficient information on the response and excitation reconstruction.

Bayesian enhancement two-stage design for single-arm phase II clinical trials with binary and time-to-event endpoints.

Simon's two-stage design is one of the most commonly used methods in phase II clinical trials with binary endpoints. The design tests the null hypothesis that the response rate is less than an uninteresting level, versus the alternative hypothesis that the response rate is greater than a desirable target level. From a Bayesian perspective, we compute the posterior probabilities of the null and alternative hypotheses given that a promising result is declared in Simon's design. Our study reveals that because the frequentist hypothesis testing framework places its focus on the null hypothesis, a potentially efficacious treatment identified by rejecting the null under Simon's design could have only less than 10% posterior probability of attaining the desirable target level. Due to the indifference region between the null and alternative, rejecting the null does not necessarily mean that the drug achieves the desirable response level. To clarify such ambiguity, we propose a Bayesian enhancement two-stage (BET) design, which guarantees a high posterior probability of the response rate reaching the target level, while allowing for early termination and sample size saving in case that the drug's response rate is smaller than the clinically uninteresting level. Moreover, the BET design can be naturally adapted to accommodate survival endpoints. We conduct extensive simulation studies to examine the empirical performance of our design and present two trial examples as applications.

Population monitoring and modelling of yellow‐shouldered parrot on Bonaire, Caribbean Netherlands

Abundance estimates based on adequate survey design and count methodology are needed for population monitoring and modelling, and for assessing the results of conservation actions taken to boost or maintain population size at desired target levels. We monitored Bonaire's population of yellow‐shouldered parrot Amazona barbadensis rothschildi using systematic distance sampling surveys in 2009–2017, and developed a Bayesian state‐space logistic model to predict changes in abundance resulting from increased human‐induced mortality in 2018–2066. Survey‐based abundance estimates (mean ± bootstrapped SE) were 0.172 ± 0.020 parrots ha‐1 and 2924 ± 340 parrots at a survey region covering 17 000 ha. Model‐based posterior distribution estimates (mean ± MCMC SD) of maximum population growth rate, maximum sustainable mortality rate, maximum sustainable mortality, population carrying capacity and equilibrium population size were 0.179 ± 0.129, 0.090 ± 0.064, 219 ± 135, 5623 ± 2043 and 2811 ± 1022 parrots. With low to moderate mortality rates (0.001– 0.100, 0.101–0.250), predicted population sizes (mean ± MCMC SD) were 2963 ± 668 and 2703 ± 1660 parrots in 2018, and 2754 ± 690 and 2297 ± 1301 parrots in 2066. With high mortality rates (0.251–0.500), predicted population sizes were 1780 ± 1160 parrots in 2018 and 26 ± 139 parrots in 2066. Because the relative importance and magnitude of human–parrot conflicts are unknown but may be unsustainable, we consider the parrot population vulnerable to the risk of extinction during the modelled time horizon. Therefore, we recommend long‐term monitoring and modelling for assessing changes in abundance and the results of conservation actions taken to keep the population above 2800 parrots in the survey region (i.e. population size N > 2.5% percentile of the posterior distribution of population carrying capacity K).

A System Dynamics Model for Predicting Supply and Demand of Medical Education Talents in China

The purpose of this paper is to study the relationship between the demand for medical talents in China and the supply of talents in medical colleges and universities. Predicting the future development of medical talents is of great significance to the establishment of medical education and the cultivation of medical talents. Based on data from China Statistical Yearbook and OECD 34 countries from 2010 to 2014, as well as some research results on overseas and domestic scholars, a system dynamics prediction model relating the supply and demand of medical education talents is developed in this paper. Actual data for the Jiangsu Province is used to demonstrate the correctness, validity and applicability of the model. Simulation results show that, under the current conditions and political environment and to maintain the current average levels of OECD 34 countries, the projected number of demand for doctors in Jiangsu in 2024 is a little more than 319,800. Based on current data, there is still quite a large gap between these indexes in China and the desired target levels. Consequently, the system and structure of medical education need to be adjusted, with the corresponding policies and management system simultaneously reformed and medical environment improved.