Airworthiness Compliance Verification Method Based on Simulation of Complex System

AbstractA study is conducted on a new airworthiness compliance verification method based on pilot-aircraft-environment complex system simulation. Verification scenarios are established by “block diagram” method based on airworthiness criteria. A pilot-aircraft-environment complex model is set up and a virtual flight testing method based on connection of MATLAB/Simulink and Flightgear is proposed. Special researches are conducted on the modeling of pilot manipulation stochastic parameters and manipulation in critical situation. Unfavorable flight factors of certain scenario are analyzed, and reliability modeling of important system is researched. A distribution function of small probability event and the theory on risk probability measurement are studied. Nonlinear function is used to depict the relationship between the cumulative probability and the extremum of the critical parameter. A synthetic evaluation model is set up, modified genetic algorithm (MGA) is applied to ascertaining the distribution parameter in the model, and a more reasonable result is obtained. A clause about vehicle control functions (VCFs) verification in MIL-HDBK-516B is selected as an example to validate the practicability of the method

Cost-effectiveness of neoadjuvant pembrolizumab plus chemotherapy with adjuvant pembrolizumab for early-stage non-small cell lung cancer in the United States

IntroductionPerioperative (neoadjuvant and adjuvant) pembrolizumab has shown favorable efficacy in patients with early-stage non-small cell lung cancer (NSCLC). This study aims to evaluate the cost-effectiveness of this treatment from the perspective of the United States healthcare payers.MethodsWe established a Markov model to compare the cost-effectiveness of perioperative pembrolizumab with that of neoadjuvant chemotherapy in 21-day cycles, utilizing data from the phase 3 KEYNOTE-671 trial. Additional data were extracted from other publications or online sources. Sensitivity analyses were conducted to evaluate the robustness of the findings. A willingness-to-pay threshold of $150,000 per quality-adjusted life-years (QALYs) gained was established. The main outcomes of this study were the measurement of QALYs, overall costs, incremental cost-effectiveness ratio (ICER), and net monetary benefit (NMB).ResultsDuring a 10-year time horizon, the total costs of perioperative pembrolizumab and the control treatment were$224,779.1 and $110,026.3, respectively. The QALYs were 4.19 and 2.97 for the two treatments, respectively, which led to an ICER of$94,222.29 per QALY gained. The NMB at the WTP threshold at $150,000 per QALY gained was$67,931.3. One-way sensitivity analysis identified the cost of pembrolizumab as the primary factor influencing cost-effectiveness. Probabilistic sensitivity analysis indicated a 97.7% probability of perioperative pembrolizumab being cost-effective at the WTP threshold.ConclusionsFrom the perspective of the United States healthcare payers, perioperative pembrolizumab is a cost-effective treatment for patients with early-stage NSCLC

Gadolinium‐Doped Iron Oxide Nanoprobe as Multifunctional Bioimaging Agent and Drug Delivery System

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116012/1/adfm201502868.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/116012/2/adfm201502868-sup-0001-S1.pd

Inefficiency and Environmental Risks associated with Nutrient Use in Agriculture within China and the UK

The stocks and flows of nitrogen (N) and phosphorus (P) were quantified for five case studies, representing contrasting agricultural systems in China and the UK. The input of nutrients exceeded the output of nutrients in agricultural products for all five systems, although to varying degrees between individual case studies.Excessive input of nutrients for each system increases the risk of negative environmental impacts on soil, air and water quality. Soils accumulate nutrient stocks due to excessive nutrient inputs, representing an under-exploited nutrient reserve that could contribute to future agriculture production. Livestock and crop production are increasingly disconnected in China. Manure application was limited to high-value fruit and vegetable crops in the systems analysed, but often without adequate accounting for the nutrient content of the applied manure.Pathways to improve the efficiency of nutrient use are identified

Delivering improved nutrient stewardship in China: the knowledge, attitudes and practices of farmers and advisers

There is a need to assess and re-orient agricultural knowledge and innovation systems (AKIS) in China, aiming to rebalance the importance of productivity alongside the stewardship of farm inputs, natural resources and broader protection of the environment; a new ethos is needed. Analysis and recommendations for this are provided

Fertilization drives distinct biotic and abiotic factors in regulating functional groups of protists in a 5-year fertilization system

IntroductionProtists play an important role in nutrient cycling, microbiome stability and soil fertility maintenance. However, the driving force of protistan functional groups remains poorly understood in agricultural ecosystems.MethodsWe investigated the impacts of fertilization regimes on the diversity, composition and functional groups of protists and further disentangled the effects of multiple factors shaping the community composition of functional groups in a 5-year fertilization regime (CK, no fertilization; M, organic fertilization; MNPK, combined inorganic and organic fertilization; NPK, inorganic fertilization).ResultsFertilization significantly changed the community composition of protists rather than diversity. The MNPK treatment significantly increased the relative abundance of phototrophs and decreased that of the parasites and consumers. Partial least squares path modeling indicated that fertilization indirectly regulated protistan consumers via changes in the P content, which affected the composition of consumers mainly by regulating fungal community composition. Soil moisture (SM) and available phosphorus (AP) were identified as the top predictors for the composition of parasites, and the composition of phototrophs was mainly affected by SM, indicating that parasites and phototrophs were more sensitive to abiotic factors in the fertilization system.DiscussionTaken together, our findings highlight that fertilization significantly affects the composition of functional groups of protists and their biotic or abiotic regulatory processes, which have implications for the potential changes in their ecosystem functions for soil management systems

Optimal timing and sequence of combining stereotactic radiosurgery with immune checkpoint inhibitors in treating brain metastases: clinical evidence and mechanistic basis

Abstract Recent evidence has shown that immune checkpoint inhibitors (ICIs) are efficacious for treating brain metastases of various primary tumors. However, the immunosuppressive tumor microenvironment and the blood–brain barrier (BBB) or blood-tumor barrier (BTB) essentially restrict the efficacy of ICIs. Stereotactic radiosurgery (SRS) can be a powerful ally to ICIs due to its trait of disrupting the BBB/BTB and increasing the immunogenicity of brain metastases. The combination of SRS + ICI has shown synergy in brain metastases in several retrospective studies. Nevertheless, the optimal schedule for the combination of SRS and ICI in brain metastases is yet to be determined. In this review, we summarized the current clinical and preclinical evidence on the timing and sequence of SRS + ICI to provide insight into the current state of knowledge about this important area in patient care

Spiculation Sign Recognition in a Pulmonary Nodule Based on Spiking Neural P Systems

The spiculation sign is one of the main signs to distinguish benign and malignant pulmonary nodules. In order to effectively extract the image feature of a pulmonary nodule for the spiculation sign distinguishment, a new spiculation sign recognition model is proposed based on the doctors’ diagnosis process of pulmonary nodules. A maximum density projection model is established to fuse the local three-dimensional information into the two-dimensional image. The complete boundary of a pulmonary nodule is extracted by the improved Snake model, which can take full advantage of the parallel calculation of the Spike Neural P Systems to build a new neural network structure. In this paper, our experiments show that the proposed algorithm can accurately extract the boundary of a pulmonary nodule and effectively improve the recognition rate of the spiculation sign