Cost-effectiveness analysis of once-daily oral semaglutide versus placebo and subcutaneous glucagon-like peptide-1 receptor agonists added to insulin in patients with type 2 diabetes in China

Introduction: Oral semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that improves glycated hemoglobin levels and body weight in patients with type 2 diabetes (T2DM). We aim to evaluate the cost-effectiveness of once-daily oral semaglutide in comparison to placebo and injectable GLP-1 RAs in Chinese patients with T2DM inadequately controlled on basal insulin.Methods: The United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS OM2.1) was used to estimate the cost-effectiveness by calculating the incremental cost-effectiveness ratio (ICER). Baseline characteristics of the simulation cohort were obtained from the PIONEER 8 trial. Utility and safety inputs were derived from a network meta-analysis of 12 trials. Direct medical costs were retrieved from published literature and discounted at an annual rate of 5%. We used a willingness-to-pay (WTP) threshold of $36,528.3 per quality-adjusted life-year (QALY) gained. Scenario analysis, and one-way and probabilistic sensitivity analysis were performed.Results: The effectiveness of oral semaglutide was 10.39 QALYs with a total cost of$30,223.10, while placebo provided 10.13 QALYs at a lower total cost of $20,039.19. Oral semaglutide was not cost-effective at an ICER of$39,853.22 and $88,776.61 per QALY compared to placebo and exenatide at the WTP. However, at an annual price of$1,871.9, it was cost-effective compared with dulaglutide, liraglutide, and lixisenatide. The model was most sensitive to the discount rate and annual cost of oral semaglutide. The price of oral semaglutide needed to be reduced to $1,711.03 per year to be cost-effective compared to placebo and other injectable GLP-1 RAs except for exenatide and semaglutide injection.Conclusion: We found that once-daily oral semaglutide, at a comparable price of semaglutide injection, proves to be a cost-effective add-on therapy to insulin for Chinese patients with T2DM, especially when compared to subcutaneous GLP-1 RAs other than injectable semaglutide and exenatide. However, to achieve cost-effectiveness in comparison to placebo, further cost reduction of oral semaglutide is necessary. The estimated annual cost of$1,711.03 for oral semaglutide demonstrates a more cost-effective option than placebo, highlighting its potential value in the management of T2DM

Many Labs 2: Investigating Variation in Replicability Across Samples and Settings

We conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings. Each protocol was administered to approximately half of 125 samples that comprised 15,305 participants from 36 countries and territories. Using the conventional criterion of statistical significance (p < .05), we found that 15 (54%) of the replications provided evidence of a statistically significant effect in the same direction as the original finding. With a strict significance criterion (p < .0001), 14 (50%) of the replications still provided such evidence, a reflection of the extremely highpowered design. Seven (25%) of the replications yielded effect sizes larger than the original ones, and 21 (75%) yielded effect sizes smaller than the original ones. The median comparable Cohen’s ds were 0.60 for the original findings and 0.15 for the replications. The effect sizes were small (< 0.20) in 16 of the replications (57%), and 9 effects (32%) were in the direction opposite the direction of the original effect. Across settings, the Q statistic indicated significant heterogeneity in 11 (39%) of the replication effects, and most of those were among the findings with the largest overall effect sizes; only 1 effect that was near zero in the aggregate showed significant heterogeneity according to this measure. Only 1 effect had a tau value greater than .20, an indication of moderate heterogeneity. Eight others had tau values near or slightly above .10, an indication of slight heterogeneity. Moderation tests indicated that very little heterogeneity was attributable to the order in which the tasks were performed or whether the tasks were administered in lab versus online. Exploratory comparisons revealed little heterogeneity between Western, educated, industrialized, rich, and democratic (WEIRD) cultures and less WEIRD cultures (i.e., cultures with relatively high and low WEIRDness scores, respectively). Cumulatively, variability in the observed effect sizes was attributable more to the effect being studied than to the sample or setting in which it was studied.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Instituto de Investigaciones Psicológicas (IIP

Product information modeling for capturing design intent for computer-aided intelligent assembly modeling

Intelligent assembly is a bottleneck to be broken with urgency in the on-going revolution of manufacturing industry. However, computer-aided assembly modeling as an important supporting technology is still suffering from the problems of too many manual interventions and low-level intelligence. An intelligent assembly modeling technology was previously developed based on design intent (DI), however there lacks systematical and supportive product information model. Consequently, a novel product information model that can capture DI for computer-aided intelligent assembly modeling is established, based on the previously developed concept of interaction feature pair (IFP). The corresponding meta class model is also constructed utilizing the object-oriented technology. On this basis, the implementation process of the product information model, as well as algorithms supporting the process of computer-aided intelligent assembly modeling, is clarified, and the algorithms include IFP identification and intelligent part matching. Computer-aided intelligent assembly modeling prototype system based on the product information model, together with a case study, validated the feasibility of the proposed technology

Adaptive Neural Control for an Uncertain 2-DOF Helicopter System with Unknown Control Direction and Actuator Faults

In accordance with the rapid development of smart devices and technology, unmanned aerial vehicles (UAVs) have been developed rapidly. The two-degree-of-freedom helicopter system is a typical UAV that is susceptible to uncertainty, unknown control direction and actuator faults. Hence, a novel adaptive neural network (NN), fault-tolerant control scheme is proposed in this paper. Firstly, to compensate for the uncertainty, a radial-basis NN was developed to approximate the uncertain, unknown continuous function in the controlled system, and a novel weight-adaptive approach is proposed to save on computational cost. Secondly, a class of Nussbaum functions was chosen to solve the unknown-control-direction issue to prevent the effect of an unknown sign for the control coefficient. Subsequently, in response to the actuator faults, an adaptive parameter was designed to compensate for the performance loss of the actuators. Through rigorous Lyapunov analyses, the designed control scheme was proven to enable the states of the closed-loop system to be semi-globally uniformly bounded and the controlled system to be stable. Finally, we conducted a numerical simulation on Matlab to further verify the validity of the proposed scheme

Spoofing Detection Algorithm Based on Pseudorange Differences

Intentional spoofing interference can cause damage to the navigation terminal and threaten the security of a global navigation satellite system (GNSS). For spoofing interference, an anti-spoofing algorithm based on pseudorange differences for a single receiver is proposed, which can be used to detect simplistic and intermediate spoofing attacks, as well as meaconing attacks. Double-difference models using the pseudorange of two adjacent epochs are established followed by the application of Taylor expansion to the position relationship between the satellite and the receiver (or the spoofer). The authenticity of the signal can be verified by comparing the results of the proposed spoofing detection algorithm with the traditional least squares method. The results will differ when spoofing is present. The parameter setting of the proposed algorithm is introduced. The algorithm has the advantage of both simplicity and efficiency and needs only a single receiver and pseudorange data. A NovAtel receiver is adopted for the actual experiments. The Texas spoofing test battery (TEXBAT), as well as two other simulation experiments are used to verify the performance of the algorithm. The simulation results validate the feasibility and effectiveness of the algorithm

Mercury (Hg) in the “Skin” of the Ocean: Dissolved Gaseous Hg, Total Hg, and Hg Redox Chemistry in Sea Surface Microlayer and Implication for Air–Sea Hg Exchange

The sea surface microlayer (SML) is the uppermost ∼1000 μm of the surface of the ocean. With distinct physicochemical properties and position relative to the adjacent subsurface waters (SSWs), the ubiquitous distribution and high dynamics of the SML greatly regulate the global air–sea gas exchange and biogeochemistry. Mercury (Hg) redox chemistry in surface seawaters and air–sea exchange of gaseous Hg (mainly Hg(0)) fundamentally control the global oceanic Hg cycle. However, the occurrence and transformation of Hg in the SML have been poorly quantified. Here we optimize the traditional SML sampling system to make it more suitable for dissolved gaseous Hg (DGM, mainly Hg(0)) sampling. We then assess the temporal and spatial variability of DGM, total Hg, dissolved organic carbon (DOC), and Hg redox chemistry in the SML and SSWs of diverse marine environments. Our data suggest a general DGM, total Hg, and DOC enrichment in the SML relative to the SSWs but with complex variability in time and space. The incubation experiments further reveal the complex characteristics of Hg redox chemistry between the SML and SSWs. We discuss important implications of the SML Hg cycle on air–sea Hg exchange and suggest wider investigations of the SML Hg cycle in the global hydrosphere