Advancing higher education and its implication towards sustainable development: Moderate role of green innovation in BRI economies.

Environmental deterioration is one of the major problems the globe is facing in the modern period. On the other hand, several groups around the world have endeavored to launch efforts to protect the planet, such as the Sustainable Development Goals. Therefore, the proposed objectives' primary duty is to strike a balance between development and environmental concerns. This study looked at 65 Belt and Road Initiative (BRI) economies to see how factors, including the economic complexity index, urbanization, ICT, higher education, and green innovation, affected carbon emissions in the presence of sustainable development. Annual time series data from 2000 to 2020 have been used in the analysis. This study employs the CC-EMG to determine the durability of the association between the variables. AMG and quantile GMM regression estimations were used to test the robustness and reproducibility of the results. The results reveal that higher education and green innovation help lower carbon emissions, whereas the economic complexity index and urbanization are beneficial for increasing economic activity and advancing information and communication technologies. The economic complexity index, ICT, and higher education are all negatively impacted by green innovation. Important policy implications of the computed coefficients for the selected and other developing markets in planning a suitable path forward to a sustainable environment are also provided.

Enhancing Performance of Single-Channel SSVEP-Based Visual Acuity Assessment via Mode Decomposition.

This study aimed to improve the performance of single-channel steady-state visual evoked potential (SSVEP)-based visual acuity assessment by mode decomposition methods. Using the SSVEP dataset induced by the vertical sinusoidal gratings at six spatial frequency steps from 11 subjects, 3-40-Hz band-pass filtering and other four mode decomposition methods, i.e., empirical mode decomposition (EMD), ensemble empirical mode decomposition (EEMD), improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN), and variational mode decomposition (VMD), were used to preprocess the single-channel SSVEP signals from Oz electrode. After comparing the SSVEP signal characteristics corresponding to each mode decomposition method, the visual acuity threshold estimation criterion was used to obtain the final visual acuity results. The agreement between subjective Freiburg Visual Acuity and Contrast Test (FrACT) and SSVEP visual acuity for band-pass filtering (-0.095 logMAR), EMD (-0.112 logMAR), EEMD (-0.098 logMAR), ICEEMDAN (-0.093 logMAR), and VMD (-0.090 logMAR) was all pretty good, with an acceptable difference between FrACT and SSVEP acuity for band-pass filtering (0.129 logMAR), EMD (0.083 logMAR), EEMD (0.120 logMAR), ICEEMDAN (0.103 logMAR), and VMD (0.108 logMAR), finding that the visual acuity obtained by these four mode decompositions had a lower limit of agreement and a lower or close difference compared to the traditional band-pass filtering method. This study proved that the mode decomposition methods can enhance the performance of single-channel SSVEP-based visual acuity assessment, and also recommended ICEEEMDAN as the mode decomposition method for single-channel electroencephalography (EEG) signal denoising in the SSVEP visual acuity assessment.

The recommended dosage regimen for caspofungin in patients with higher body weight or hypoalbuminaemia will result in low exposure: Five years of data based on a population pharmacokinetic model and Monte-Carlo simulations.

Background: To develop a population pharmacokinetic (PPK) model for caspofungin, identify parameters influencing caspofungin pharmacokinetics, and assess the required probability of target attainment (PTA) and cumulative fraction of response (CFR) for various dosing regimens of caspofungin in all patients and intensive care unit (ICU)-subgroup patients. Method: The general PPK model was developed based on data sets from all patients (299 patients). A ICU-subgroup PPK model based on data sets from 136 patients was then analyzed. The effects of demographics, clinical data, laboratory data, and concomitant medications were tested. Monte-Carlo simulations (MCS) were used to evaluate the effectiveness of different caspofungin dosage regimens. Results: One-compartment model best described the data of all patients and ICU patients. Clearances (CL) were 0.32 L/h and 0.40 L/h and volumes of distribution (V) were 13.31 L and 10.20 L for the general and ICU-subgroup PPK models, respectively. In the general model, CL and V were significantly associated with albumin (ALB) concentration and body weight (WT). In the ICU-subgroup model, CL was associated with WT. The simulated exposure in ICU patients was lower than that in all patients (p < 0.05). MCS indicated that higher caspofungin maintenance doses of 70-150 mg may achieve target CFR of >90% for patients with higher WT (>70 kg) or with C. albicans or C. parapsilosis infections, and especially for ICU patients with hypoalbuminaemia. Conclusion: The PPK model and MCS presented in the study demonstrated that the recommended dosage regimen for caspofungin in patients with higher body weight or hypoalbuminaemia will result in low exposure.

Cost-effectiveness analysis of 4 GLP-1RAs in the treatment of obesity in a US setting.

Background: The number of obese people continues to increase worldwide, and obesity-related complications add to every country's health burden. Consequently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), are attracting increasing attention. This study sought to assess the cost effectiveness for weight loss of 4 GLP-1RAs in adult patients with obesity in the United States. Methods: Four GLP-1RA groups that received Liraglutide (1.8 mg QD), Semaglutide (1.0 mg QW), Dulaglutide (1.5 mg QW), or Exenatide (10 µg BID), and one no-treatment group were compared using a decision-tree model. All the estimated parameters were derived from published articles. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were adopted as the study endpoints. We analyzed the results with the willingness-to-pay (WTP) threshold, and conducted deterministic and probabilistic sensitivity analyses. Results: The GLP-1RAs produced effective weight-loss results; however, not all the GLP-1RAs were cost effective compared to no treatment based on a WTP threshold of $195000/QALY. Among the 4 GLP-1RAs, Semaglutide provided a cost-effective strategy with an ICER of $135467/QALY. The sensitivity analyses showed that these results are reliable. Conclusions: Among the 4 GLP-1RAs, Semaglutide was the most cost-effective obesity medication.

Real-time, precise, rapid and objective visual acuity assessment by self-adaptive step SSVEPs.

Objective. This study aimed to explore an online, real-time, and precise method to assess steady-state visual evoked potential (SSVEP)-based visual acuity more rapidly and objectively with self-adaptive spatial frequency steps.Approach. Taking the vertical sinusoidal reversal gratings with different spatial frequencies and temporal frequencies as the visual stimuli, according to the psychometric function for visual acuity assessment, a self-adaptive procedure, the best parameter estimation by sequential testing algorithm, was used to calculate the spatial frequency sequence based on all the previous spatial frequencies and their significance of the SSVEP response. Simultaneously, the canonical correlation analysis (CCA) method with a signal-to-noise ratio (SNR) significance detection criterion was used to judge the significance of the SSVEP response.Main results.After 18 iterative trails, the spatial frequency to be presented converged to a value, which was exactly defined as the SSVEP visual acuity threshold. Our results indicated that this SSVEP acuity had a good agreement and correlation with subjective Freiburg Visual Acuity and Contrast Test acuity, and the test-retest repeatability was also good.Significance. The self-adaptive step SSVEP procedure combined with the CCA method and SNR significance detection criterion appears to be an alternative method in the real-time SSVEP acuity test to obtain objective visual acuity more rapidly and precisely.

Does Oblique Effect Affect SSVEP-Based Visual Acuity Assessment?

This study aimed to explore whether there was an effect on steady-state visual evoked potential (SSVEP) visual acuity assessment from the oblique effect or the stimulus orientation. SSVEPs were induced by seven visual stimuli, e.g., the reversal sinusoidal gratings with horizontal, two oblique, and vertical orientations, reversal checkerboards with vertical and oblique orientations, and oscillating expansion-contraction concentric-rings, at six spatial frequency steps. Ten subjects participated in the experiment. Subsequently, a threshold estimation criterion was used to determine the objective SSVEP visual acuity corresponding to each visual stimulus. Taking the SSVEP amplitude and signal-to-noise-ratio (SNR) of the fundamental reversal frequency as signal characteristics, both the SSVEP amplitude and SNR induced by the reversal sinusoidal gratings at 3.0 cpd among four stimulus orientations had no significant difference, and the same finding was also shown in the checkerboards between vertical and oblique orientation. In addition, the SSVEP visual acuity obtained by the threshold estimation criterion for all seven visual stimuli showed no significant difference. This study demonstrated that the SSVEPs induced by all these seven visual stimuli had a similarly good performance in evaluating visual acuity, and the oblique effect or the stimulus orientation had little effect on SSVEP response as well as the SSVEP visual acuity.

Cost-effectiveness of pembrolizumab for treatment of platinum-resistant recurrent or metastatic head and neck squamous cell carcinoma in China: an economic analysis based on a randomised, open-label, phase III trial.

BACKGROUND: Pembrolizumab was recently demonstrated to have survival benefit in patients with recurrent or metastatic head and neck squamous cell carcinoma (r/mHNSCC). However, the cost-effectiveness of pembrolizumab versus chemotherapy in China remains uncertain. OBJECTIVE: This analysis aimed to describe the cost-effectiveness of pembrolizumab versus standard-of-care (SOC) therapy in r/mHNSCC in China. DESIGN: A Markov model consisting of three health states (stable, progressive and dead) was developed to compare the cost and effectiveness of pembrolizumab with SOC in platinum-resistant r/mHNSCC. Model inputs for transition probabilities and toxicity were collected from the KEYNOTE-040 trial, while health utilities were estimated from a literature review. Cost data were acquired for the payer's perspective in China. Costs and outcomes were discounted at an annual rate of 3.0%. Sensitivity analyses were conducted to test the uncertainties surrounding model parameters. OUTCOME MEASURES: The primary outcome was incremental cost-effectiveness ratios (ICERs), which were calculated as the cost per quality-adjusted life years (QALYs). RESULTS: The total mean cost of pembrolizumab and SOC was US$45 861 and US$41 950, respectively. As for effectiveness, pembrolizumab yielded 0.31 QALYs compared with 0.25 QALYs for SOC therapy. The ICER for pembrolizumab versus SOC was US$65 186/QALY, which was higher than the willingness-to-pay threshold (WTP) of US$28 130/QALY in China. The univariate sensitivity analysis indicated that utility values for progressive state, probability from stable to progressive in the SOC group, as well as cost of pembrolizumab were the three most influential variables on ICER. The probabilistic sensitivity analysis demonstrated that standard therapy was more likely to be cost-effective compared with pembrolizumab at a WTP value of US$28 130/QALY. Results were robust across both univariate analysis and probabilistic sensitivity analysis. CONCLUSIONS: Pembrolizumab is not likely to be a cost-effective strategy compared with SOC therapy in patients with platinum-resistant r/mHNSCC in China. TRIAL REGISTRATION NUMBER: NCT02252042; Post-results.

Assessment of Human Visual Acuity Using Visual Evoked Potential: A Review.

Visual evoked potential (VEP) has been used as an alternative method to assess visual acuity objectively, especially in non-verbal infants and adults with low intellectual abilities or malingering. By sweeping the spatial frequency of visual stimuli and recording the corresponding VEP, VEP acuity can be defined by analyzing electroencephalography (EEG) signals. This paper presents a review on the VEP-based visual acuity assessment technique, including a brief overview of the technique, the effects of the parameters of visual stimuli, and signal acquisition and analysis of the VEP acuity test, and a summary of the current clinical applications of the technique. Finally, we discuss the current problems in this research domain and potential future work, which may enable this technique to be used more widely and quickly, deepening the VEP and even electrophysiology research on the detection and diagnosis of visual function.

Anti-fatigue Performance in SSVEP-Based Visual Acuity Assessment: A Comparison of Six Stimulus Paradigms.

PURPOSE: The occurrence of mental fatigue when users stare at stimuli is a critical problem in the implementation of steady-state visual evoked potential (SSVEP)-based visual acuity assessment, which may weaken the SSVEP amplitude and signal-to-noise ratio (SNR) and subsequently affect the results of visual acuity assessment. This study aimed to explore the anti-fatigue performance of six stimulus paradigms (reverse vertical sinusoidal gratings, reverse horizontal sinusoidal gratings, reverse vertical square-wave gratings, brief-onset vertical sinusoidal gratings, reversal checkerboards, and oscillating expansion-contraction concentric rings) in SSVEP acuity assessment. METHODS: Based on four indices of α + θ index, pupil diameter, National Aeronautics and Space Administration Task Load Index (NASA-TLX), and amplitude and SNR of SSVEPs, this study quantitatively evaluated mental fatigue in six SSVEP visual attention runs corresponding to six paradigms with 12 subjects. RESULTS: These indices of mental fatigue showed a good agreement. The results showed that the paradigm of motion expansion-contraction concentric rings had a superior anti-fatigue efficacy than the other five paradigms of conventional onset mode or pattern reversal mode during prolonged SSVEP experiment. The paradigm of brief-onset mode showed the lowest anti-fatigue efficacy, and the other paradigms of pattern reversal SSVEP paradigms showed a similar anti-fatigue efficacy, which was between motion expansion-contraction mode and onset mode. CONCLUSION: This study recommended the paradigm of oscillating expansion-contraction concentric rings as the stimulation paradigm in SSVEP visual acuity because of its superior anti-fatigue efficacy.

Comparison of the performance of six stimulus paradigms in visual acuity assessment based on steady-state visual evoked potentials.

PURPOSE: There are several stimulus paradigms used in objective visual acuity assessment based on steady-state visual evoked potentials (SSVEPs). The aim of this study was to explore the difference and performance of common used six stimulus paradigms (reverse vertical sinusoidal gratings, reverse horizontal sinusoidal gratings, reverse vertical square-wave gratings, brief-onset vertical sinusoidal gratings, reversal checkerboards and oscillating expansion-contraction concentric-rings) of SSVEP acuity assessment. METHODS: We tested subjective visual acuity both by tumbling E and Freiburg Visual Acuity and Contrast Test (FrACT) in 11 subjects. SSVEPs were induced by 11 spatial frequencies for each paradigm, and then a threshold determination criterion was used to define the objective SSVEP visual acuity. RESULTS: After SSVEP signal analysis, we found there was difference in SSVEP response of harmonic components and no difference in sensitive electrode placement for the six paradigms. We selected six electrodes (PO3, POz, PO4, O1, Oz and O2) as the sensitive electrodes to use in data processing for each paradigm. The results showed that except for brief-onset vertical sinusoidal gratings, the correlation and agreement between objective SSVEP and subjective FrACT acuity were all quite good, demonstrating good performance in acuity detection for the rest five paradigms. CONCLUSION: Except for brief-onset vertical sinusoidal gratings, all the five stimulus paradigms of reverse vertical sinusoidal gratings, reverse horizontal sinusoidal gratings, reverse vertical square-wave gratings, reversal checkerboards and oscillating expansion-contraction concentric-rings performed quite well in objective SSVEP visual acuity assessment.

Objective and quantitative assessment of interocular suppression in strabismic amblyopia based on steady-state motion visual evoked potentials.

In this study, we aimed to explore an objective, sensitive and quantitative measurement of interocular suppression in strabismic amblyopia. We compared 11 strabismic subjects with 12 normal vision subjects to explore the different response characterizations in normal eyes, nondominant and dominant eyes of strabismic subjects by using steady-state motion visual evoked potentials (SSMVEPs). Stimulation at different temporal frequencies was presented to two eyes by using an interocular dichoptic technique. Furthermore, canonical correlation analysis (CCA), signal-to-noise ratio (SNR) and some statistical methods, such as the paired t-test, analysis of variance (ANOVA) and correlation analysis, were used to analyze electroencephalography (EEG) signals. We proposed two indices-divergence J and suppression imbalance (SI) to describe the deficits in interocular suppression-and one index - mask attenuation coefficient (MAC)- to describe the influence of a dichoptic mask from the dominant eyes to nondominant eyes of strabismic subjects. A significant difference was found between nondominant and dominant eyes of strabismic subjects in SSMVEP response and SNR value while no apparent difference was observed between the two eyes in subjects with normal vision. There was a strong linear correlation between divergence J, SI and visual acuity difference of two eyes both in strabismic amblyopia and normal vision. A linear correlation was also found between visual acuity difference and MAC in patients with strabismic amblyopia. Our findings suggest that SSMVEPs can be an objective and quantitative method for measuring the interocular suppression in strabismus and assessing the deficits of strabismic amblyopia.

Objective and quantitative assessment of visual acuity and contrast sensitivity based on steady-state motion visual evoked potentials using concentric-ring paradigm.

PURPOSE: The traditional assessment of visual acuity and contrast sensitivity depends more on subjective judgments. Steady-state motion visual evoked potentials (SSMVEPs) can provide an objective and quantitative method to evaluate visual functions such as visual acuity and contrast sensitivity. Here, we explored the possibility of objective SSMVEP visual acuity and contrast sensitivity testing, and compared its performance with that of psychophysical methods. METHODS: In this study, we designed a specific concentric ring with oscillating expansion and contraction SSMVEP paradigm to assess visual acuity and contrast sensitivity. By changing the parameters of the paradigm, the SSMVEP paradigm with different contrasts and spatial frequencies corresponding to different visual acuity and contrast sensitivity was designed. Moreover, we proposed a threshold determination criterion to define the corresponding objective SSMVEP visual acuity and contrast sensitivity. RESULTS: We tested visual acuity and contrast sensitivity of sixteen healthy adults utilizing this paradigm with an electroencephalography system. Our data suggested that there was no significant difference between objective visual acuity and contrast sensitivity measurements based on the SSMVEPs and subjective psychophysical ones. CONCLUSION: Our study proved that SSMVEPs can be an objective and quantitative method to measure visual acuity and contrast sensitivity.

Pharmacokinetic/Pharmacodynamic Analysis of Isavuconazole Against Aspergillus spp. and Candida spp. in Healthy Subjects and Patients With Hepatic or Renal Impairment by Monte Carlo Simulation.

The aim of this pharmacokinetic/pharmacodynamic (PK/PD) study is to evaluate the efficacy of various isavuconazole dosing regimens for healthy individuals and patients with hepatic or renal impairment against Aspergillus spp. and Candida spp. Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamics (PD) data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (AUC/MIC) targets of isavuconazole. A clinically recommended dosage regimen of isavuconazole (200 mg qd) obtained high cumulative fraction of response values of > 90% for all subjects against A. fumigatus, A. flavus, A. nidulans, A. terreus, A. versicolor, C. parapsilosis and C. tropicalis. For patients with mild or moderate hepatic impairment, the dosage should be halved only when treating invasive fungal infections caused by C. albicans, C. parapsilosis or C. tropicalis. However, dose adjustment is unlikely to be required in mild to severe renal impairment patients because all cumulative fraction of response values were similar to those of comparing with healthy subjects. Notably, all isavuconazole dosing regimens were not effective against C. glabrata and C. krusei in all subjects. These PK/PD-based simulations rationalize and optimize the dosage regimens of isavuconazole for healthy individuals and patients with hepatic or renal impairment against Aspergillus spp. and Candida spp.

Pharmacokinetic/pharmacodynamic adequacy of echinocandins against Candida spp. in intensive care unit patients and general patient populations.

This study evaluated whether contemporary echinocandin regimens achieved pharmacokinetic/pharmacodynamic targets in ICU patients and general patient populations (GPPs) and assessed caspofungin (CAS) regimens in hepatic impairment (HI) patients. A Monte Carlo simulation was performed using previously published data. Recommended dosing regimens of echinocandins in ICU patients, GPPs and healthy volunteers were evaluated: 70mg loading dose then 50mg maintenance dose (70/50mg) for CAS; 100mg q24h for micafungin (MCF); and 200/100mg for anidulafungin (ANF). Moreover, CAS 70mg and 100mg q24h in GPPs, and CAS 70/50mg and 70/35mg in mild and moderate HI patients, respectively, were evaluated. Cumulative fraction of response (CFR) was calculated for each dosing regimen. For Candida albicans, CFRs for the recommended doses of CAS, MCF and ANF were 95.8%, 13.5% and 50.5% in ICU patients and 96.3%, 42.4% and 61.6% in GPPs, respectively; for Candida glabrata, CFRs were 99.4%, 90.6% and 44.6% in ICU patients and 99.5%, 97.1% and 59.8% in GPPs. For Candida parapsilosis, CFRs of echinocandins for standard regimens were <70%; only CAS 100mg q24h achieved the target CFR. CAS 70/50mg and 70/35mg in mild and moderate HI patients were appropriate. Considerable interindividual variability was observed. For C. albicans and C. glabrata, CAS is good choice both for ICU and other patient populations, but for C. parapsilosis an increased dose should be considered. For MCF and ANF, administering higher doses with longer dosing intervals achieves better target attainment and should be investigated in clinical trials.