Managing delayed or missed pregabalin doses in patients with focal epilepsy: a Monte Carlo simulation study.

BACKGROUND: Delayed or missed doses are inevitable in epilepsy pharmacotherapy. The current remedial measures recommended by the United States Food and Drug Administration (FDA) for non-adherence are generic and lack clinical evidence. AIM: To assess remedial strategies for delayed or missed pregabalin doses in patients with epilepsy using Monte Carlo simulations. METHOD: Monte Carlo simulations were performed using a published population pharmacokinetic model for pregabalin. The applicability of five proposed remedial regimens as well as FDA recommendations was evaluated by simulating various poor adherence scenarios in eight populations, including those with renal dysfunction. RESULTS: All proposed remedial strategies were associated with delay duration and renal function. When delays are relatively short, an immediate regular dose is advised. The cut-off time points for taking the regular dose as a remedial regimen were 1, 2, 4, and 12 h for patients with mild renal impairment and normal renal function, moderate renal impairment, severe renal impairment, and end-stage renal disease, respectively. However, when delay aligns closely with a dosing interval, a regular dose combined with a partial dose proves effective. Generally, supplementing 1.3-fold the regular dose at the next scheduled time adequately compensates for the missed dose. CONCLUSION: Model-based simulations provided quantitative evidence for the effectiveness and feasibility of remedial strategies for missed or delayed pregabalin doses.

The impact of industrial structure adjustment on the spatial industrial linkage of carbon emission: From the perspective of climate change mitigation.

Industrial structure adjustment is an effective way to reduce carbon emissions. When adjusting the industrial structure, changes in the input and output of industrial sectors in one region may cause changes in industrial sectors of other regions, resulting in inter-regional industrial linkages. What is the impact of industrial structure adjustment on the linkages, and how does it impact climate change? The modified gravity model combines the influence and inductive coefficients to build the carbon emission industrial spatial linkage network (ISL) using social network analysis (SNA) in this work with the data of China's 2008-2019 provincial carbon emissions. The impact of industrial structure adjustment on carbon emission industrial spatial linkage network and its effect on climate change mitigation are explored with the help of the STIRPAT model and quality assurance procedure (QAP). The results of this study are as follows: (1) The provincial carbon emissions under industrial spatial linkages show significant network characteristics, the network density increased from 0.1437 in 2008 to 0.323 in 2019. (2) There is a significant spatial spillover effect in the industrial spatial linkage network (2019) centered on Shandong and Jiangsu. The provinces can be divided into 4 blocks, which play different roles in the network. (3) The industrial structure upgrading can significantly promote the carbon emission industrial linkage network and mitigate climate change. (4) The industrial structure rationalization can promote the development of the network and mitigate climate change in the early and late development stages of carbon emissions industrial linkage. In addition, it is necessary for the government to pay more attention to the development level of the carbon emission spatial industrial linkage network when implementing industrial structure adjustment in response to climate change.

Population Pharmacokinetic Modeling Using Polymyxin B Free Plasma Concentrations From Published Reports and Evaluation of Dosage Regimens Based on Monte Carlo Simulation in Critically Ill Patients.

A population pharmacokinetic (pop PK) model of polymyxin B was developed using nonlinear mixed-effects (NONMEM) modeling based on free plasma concentrations to determine whether dose adjustment is required in critically ill patients. One thousand pharmacokinetic profiles for virtual patients with a body weight of 70 kg were simulated using Monte Carlo simulation at different dose scenarios, and area under the concentration-time curve of free drug (fAUC) was computed. The probability of target attainment (PTA) at each minimum inhibitory concentration (MIC) was calculated using fAUC/MIC as a pharmacokinetic/pharmacodynamic (PK/PD) index. The final population PK model was a 2-compartment model. PTA showed that 3.5 mg/kg/day regimens of polymyxin B effectively achieved the fAUC/MIC target of 10 (one log10 kill) against Pseudomonas aeruginosa strains with MIC of 1 mg/L or less (PTA,  90.7% or greater), while the dose regimen were ineffective against strains with an MIC of 2 mg/L or greater (PTA, 56.9% or less). For Klebsiella pneumoniae, the fAUC/MIC target of 17.4 (one log10 kill) was achieved in more than 90.4% of cases for MIC of 0.5 mg/L or less with 3 mg/kg/day regimens. However, the PTA decreased dramatically as MICs increased above 1 mg/L (PTA, 56.1% or less). The polymyxin B dosage regimen of 3.5 mg/kg/day and 3 mg/kg/day are sufficient to treat P. aeruginosa infections with an MIC of 1 mg/L or less and K. pneumoniae infections with an MIC of 0.5 mg/L or less, respectively. The current recommended dose (1.5-3 mg/kg/day) of polymyxin B appears inadequate to attain the PK/PD target for therapeutic efficacy against infections caused by P. aeruginosa and K. pneumoniae isolates when MIC is above the values.

How do resource dependence and technological progress affect carbon emissions reduction effect of industrial structure transformation? Empirical research based on the rebound effect in China.

Under the guidance of carbon peak and carbon neutral targets, the industrial structure transformation is vital for carbon emissions reduction in China. However, there is a rebound effect of carbon emissions during the industrial structure transformation. Resource dependence and technological progress have significant impacts on industrial structure transformation and its carbon reduction effect. This paper explores how industrial structure transformation under resource dependence causes the rebound effect from a technological progress perspective. The key results indicate that (1) resource dependence distorts the carbon emissions reduction effect of industrial structure transformation; (2) with the development of technology, the industrial structure upgrading under resource dependence could cause an increase on carbon emissions at the beginning, but the increase would be weakened subsequently, displaying a two-stage feature; (3) the industrial structure rationalization under resource dependence reduces carbon emissions at first, but the reduction would be weakened as the technology develops, then industrial structure's rationalization shows an insignificant impact on carbon emissions, and finally reduces carbon emissions again, presenting a four-stage characteristic; (4) environmental protection technology can correct the distortion effect of resource dependence on the industrial structure rationalization and amplify the industrial structure rationalization's reduction effects on carbon emissions; (5) with the development of energy-saving technology, industrial structure rationalization has a paradoxical impact on carbon emissions, the industrial structure rationalization first reduces, then increases, and finally reduces carbon emissions, indicating an inverted "N" relationship. Finally, policy recommendations for carbon emissions reduction are proposed from the perspective of industrial structure transformation and technological progress.

Industrial Structure Adjustment and Regional Green Development from the Perspective of Mineral Resource Security.

Mineral resource security is the premise and foundation of the regional green rise strategy. And the adjustment of industrial structure is an effective way to relieve the pressure of the current green economy transformation. Based on the Shift-share Method and the Spatial Durbin model, this paper takes 30 regions in China from 2006 to 2017 as examples to study the impact of industrial structure adjustment on China's green development from the perspective of mineral resource security. The empirical results show that: China is still in the process of industrial transfer. The dynamic effect of industrial structure promotes green development from the perspective of mineral resource security, while its static effect inhibits green development from the perspective of mineral resource security. The spatial spillover effect of the industrial structure affecting green development from the perspective of mineral resource security is significant. The static structural effect of the tertiary industry promotes the green development of the region, and it has a significant negative impact on neighboring areas, while the secondary industry's static structural effect has the opposite effect.

Open reduction and internal fixation of mandibular condylar fractures: A national inpatient sample analysis, 2005-2014.

The purpose of this study was to compare outcomes of open reduction and internal fixation (ORIF) versus closed reduction (CR) for mandibular condylar fractures.Patients included in the National Inpatient Sample (NIS) database (2005-2014) who were admitted to the hospital for unilateral mandibular condylar fracture were included in the analysis. Patient characteristics and clinical outcomes were compared between those who received ORIF and those receiving CR. Logistic regression analysis was performed to estimate odds ratios (ORs) for each aspect of the main observed events.NIS data of 12,303 patients who underwent ORIF and 4310 patients who underwent CR were analyzed. Compared to CR, ORIF had an increased risk of longer hospital stay (adjusted OR [aOR] = 1.78, 95% confidence intervals [CIs] = 1.51-2.09), higher total medical cost (aOR = 2.57, 95% CI = 2.17-3.05), and hematoma development (aOR = 10.66, 95% CI = 1.43-75.59), but had a lower risk of having wound complications (aOR = 0.86, 95% CI = 0.79-0.93).Patients with mandibular condylar fractures who receive ORIF have greater risk of having an extended hospital stay, higher total medical costs, and hematoma development but lower risk of experiencing wound complications compared to those who receive CR.

[Ozone Deposition and Risk Assessment for a Winter Wheat Field:Partitioning Between Stomatal and Non-stomatal Pathways].

To better understand the ozone deposition and risk assessment over agroecosystems based on the ozone flux indices, an eddy-covariance system was used for measuring the ozone deposition continuously and dynamically in a winter wheat field. We analyzed the variations in ozone concentration, total ozone flux, and stomatal and non-stomatal flux. The relationships between stomatal/non-stomatal ozone deposition velocity and the main meteorological factors were investigated. Finally, the yield losses of winter wheat based on the ozone-dose index (AOT40) and ozone flux index (DFs06) were calculated. Results showed that average daily ozone concentration (cO3) was 32.9 nL·L-1. The daytime (08:00-18:00) and nighttime total ozone flux (FO3) were -7.6 nmol·(m2·s)-1 and -3.1 nmol·(m2·s)-1, respectively, and the mean diurnal FO3 was -5.1 nmol·(m2·s)-1. The mean daily stomatal ozone flux (Fs) and non-stomatal ozone flux (Fns) ranged from 0 to -5.1 nmol·(m2·s)-1 and from -1.43 to -10.31 nmol·(m2·s)-1, respectively. The mean diurnal Fs and Fns were -1.43 nmol·(m2·s)-1 and -3.66 nmol·(m2·s)-1. High solar radiation (SR), high temperature (T), and moderate humidity were used to analyze stomatal ozone deposition; high SR, moderate T, and high humidity were suitable to analyze non-stomatal ozone deposition. The cumulative total ozone flux (DFO3), cumulative stomatal ozone flux (DFs), and cumulative non-stomatal ozone flux (DFns) were 31.58, 9.99, and 21.59 mmol·m-2 during the entire experimental period, and DFs and DFns accounted for 32% and 68% of DFO3. The ranges of yield loss in winter wheat were estimated at 11.58%-20.37% and 20%-23.56% using different assessment models based on the ozone dose index AOT40 and ozone flux index DFs06, respectively.

Development of immunochromatography strip-test using nanocolloidal gold-antibody probe for the rapid detection of aflatoxin B1 in grain and feed samples.

An immunochromatography (ICG) strip test using a nanocolloidal gold-antibody probe was developed and optimized for the rapid detection of aflatoxin B1 (AFB1). A monoclonal antibody specific to AFB1 was produced from the cloned hybridoma cell (AF78), coupled with nanocolloidal gold, and distributed on the conjugate pad of the ICG strip test. The visual detection limit of the ICG strip test was 0.5 ng/ml, and this method showed a cross-reaction to aflatoxin B2, G1, and G2. In total, 172 grain and feed samples were collected and analyzed by both the ICG strip test and HPLC. The results of the ICG strip test showed a good agreement with those obtained by HPLC. These results indicated that the ICG strip test has a potential use as a rapid and cost-effective screening tool for the determination of AFB1 in real samples and could be applied to the preliminary screening of mycotoxin in food and agricultural products, generating results within 15 min without complicated steps.

[China's environmental load and environmental depressurization analysis].

Based on material flow accounting and related indicators, an indicator, domestic environmental load, is formulated to measure the aggregate environmental pressure of a nation. Combining this indicator with the gross national product, an indicator for environmental efficiency is derived. The domestic environmental load is then decomposed into the rebound effect caused by economic growth and the depressurization effect induced by the efficiency increase. A case study was carried out for the Chinese economy to investigate its domestic environmental load, environmental efficiency and the rebound and depressurization effects. Results show that the environmental efficiency of the Chinese economy increased during the study period with an annual rate of 5.6%, indicating that a certain degree of depressurization was achieved. However, the rebound effect caused by economic growth was much greater than the depressurization effect induced by the efficiency increase,resulting in a considerable increase in the domestic environmental load (the annual growth rate was 3.8%). The Chinese economy is characterized by high environmental pressure and it is hard to achieve absolute depressurization.