Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients.

BACKGROUND: Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children. AIMS: The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients. METHODS: A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range. RESULTS: For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose. CONCLUSION: It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.

Global, Regional, and National Incidence and Year Lived with Disability for Benign Prostatic Hyperplasia from 1990 to 2019.

The objective of this study is to provide comprehensive and up-to-date estimates on the disease burden of BPH in 204 countries and territories between 1990 and 2019. Data about incidence, year lived with disability (YLD), and their age-standardized rates (ASRs) for 21 regions, 5 Socio-demographic Index (SDI) quintiles, 204 countries and territories, and 12 age categories from 1990 to 2019 were obtained from the Global Burden of Disease 2019 study. Estimated annual percentage changes (EAPCs) of the ASRs and the associations between SDI and the ASRs were estimated. The effects of population growth, population aging, and age-specific rate on the changes in the absolute numbers of incidence and YLD were quantified. Globally, there were 11.26 million (95% uncertainty interval [UI]: 8.79, 14.46) new cases and 1.86 million (95%UI: 1.13, 2.78) YLD due to BPH in 2019. The global ASRs of incidence (EAPC: -0.031, 95% CI: -0.050, -0.012) and YLD (EAPC: -0.058, 95% CI: -0.084, -0.031) decreased slightly from 1990 to 2019, whereas the absolute numbers increased dramatically from 1990 (incidence by 105.7% and YLD by 110.6%), mainly driven by the population growth (53.5% for incidence and 54.4% for YLD) and population aging (55.7% for incidence and 63.2% for YLD). The burden of BPH varied markedly among different regions, socioeconomic status, and countries. As the population is growing and aging, great efforts are required to develop effective prevention, treatment and management strategies to meet the high and increasing burden of BPH worldwide.

Benchmark Status of Women Interventional Radiologists in China.

PURPOSE: To evaluate the current status of women interventional radiologists in China and discuss possible measures to boost their representation in this male-dominated field for a more diverse workplace environment in the future. MATERIALS AND METHODS: The list of Chinese interventional radiologists obtained from the Chinese College of Interventionalists was retrospectively reviewed. Key information was extracted from the database, including sex, chronologic trends of representation of women interventional radiologists, position, education level, geographic distribution, interventional radiology (IR) practice time, departmental affiliation, and hospital classification. RESULTS: Of the 13,855 entries, 7,324 (52.9%) were interventional radiologists having valid information. Among them, 684 (9.3%) were identified as women. The number of women interventional radiologists has continued to increase since the first woman registered in 1992. The average age of women interventional radiologists was 39.1 years ± 5.7 (range, 26-50). The majority of them were attending physicians (n = 280; 40.9%) with a bachelor's degree (n = 363; 53.1%). Most women interventional radiologists (n = 215, 31.4%) joined this specialty 5-9 years after becoming physicians, whereas 128 (18.7%) started practicing IR from the very beginning. A total of 42.4% of women interventional radiologists were from the departments of IR and cardiology. CONCLUSIONS: Although the total number shows an upward trend, women interventional radiologists are still underrepresented. Education level, geographic areas, and other socioeconomic factors may simultaneously influence the population size of women interventional radiologists in China.

Spatial distribution, source analysis, and ecological risk assessment of PBDEs in river sediment around Taihu Lake, China.

The distribution and composition of organic pollutants in sediment are affected by the source and regional environment. To understand the characteristics and risk of polybrominated diphenyl ethers (PBDEs) in the area around Taihu Lake, composite sediment samples (n = 41) were collected in rivers around Taihu Lake to explore the level, spatial distribution, and source of PBDEs. The results showed that the most abundant BDE congener in river sediment was BDE209, followed by BDE99 and BDE47, with median values of 48.7, 2.17, and 1.52 ng g-1, respectively. Concentrations of PBDEs in sediments from northern rivers were significantly higher than those from other areas, but the overall risk was at a moderate-lower level compared with research results in other references. Results of principle component analysis (PCA) and source characteristics analysis revealed that most of PBDEs in river sediments around Taihu Lake were mixture of multiple sources, which mainly originated from atmospheric deposition, industrial wastewater, and municipal sewage. TOC showed good correlations with most PBDEs, which implied that PBDE components were influenced by sediment organic matter. Meanwhile, the risk of PBDEs in river sediments in this study area is a moderate-lower level.

Multicentric Assessment of the Hong Kong Liver Cancer Staging System in Chinese Patients Following Transarterial Chemoembolization.

PURPOSE: We aimed to validate the performance of the hepatitis B-based Hong Kong Liver Cancer (HKLC) staging system compared with the Barcelona Clinic Liver Cancer (BCLC) staging system in Chinese hepatocellular carcinoma (HCC) patients treated with conventional transarterial chemoembolization (TACE) as the initial treatment. MATERIALS AND METHODS: The study was approved by the Institutional Review Boards at all participating centers. This retrospective study included 715 patients with HCC who underwent TACE as the initial treatment between January 2008 and December 2016 at three Chinese institutions. All of the patients calculated HCC stage using 5-substage HKLC (HKLC-5), 9-substage HKLC (HKLC-9), and the BCLC system. Based on overall survival (OS), these three staging systems' performance on treatment outcome prediction were compared using C statistic, Akaike information criterion (AIC), area under the receiver operating characteristic curve (AUC), linear trend Chi-square, likelihood ratio Chi-square, and calibration plots, respectively. RESULTS: The median OS was 10.1 months. Compared with the BCLC system, the HKLC system, especially HKLC-9, showed better performance on survival prediction (HKLC-9: C = 0.689, AIC = 6646.162; HKLC-5: C = 0.683, AIC = 6662.663; BCLC: C = 0.680, AIC = 6654.146), homogeneity (likelihood ratio Chi-square: HKLC-9 = 232.38, HKLC-5 = 215.87, and BCLC = 224.39, P < 0.001), and calibration (R2: HKLC-9 = 0.923, HKLC-5 = 0.916, and BCLC = 0.914). HKLC-9 outperformed on AUC at 6-, 12-, and 24-month survival prediction than HKLC-5 and BCLC. BCLC showed better performance on monotonicity (linear trend Chi-square: HKLC-9 = 121.641, HKLC-5 = 117.389, and BCLC = 125.752; P < 0.001). CONCLUSIONS: Combining survival prediction, discrimination, and calibration, the HKLC, especially HKLC-9 system, performed better for Chinese patients treated with TACE than the BCLC system.

Process Safety Assessment of the Iron-Catalyzed Direct Olefin Diazidation for the Expedient Synthesis of Vicinal Primary Diamines.

We report herein a process safety assessment of the iron-catalyzed direct olefin diazidation for the preparation of a broad range of synthetically valuable vicinal primary diamines. Differential scanning calorimetry analysis of the corresponding reagents, intermediates, and a list of representative diazide/diaminium salt products revealed that all of them are thermal stable at the reaction temperature. The drop weight test of the diazides suggested that they are moderately impact-sensitive. Guided by this assessment, an optimized olefin diazidation/diamination procedure has been developed which allows for the gram-scale diaminium salt synthesis without purification of the diazide intermediate.

Assessment of pathological complete response to preoperative chemoradiotherapy by means of multiple mathematical models of diffusion-weighted MRI in locally advanced rectal cancer: A prospective single-center study.

PURPOSE: To assess stretched-exponential, mono-exponential and intravoxel incoherent motion (IVIM) models of diffusion-weighted MRI(DWI) in predicting pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in rectal cancer patients. MATERIALS AND METHODS: This prospective study recruited 98 consecutive patients with locally advanced rectal cancer who underwent 3 Tesla MR examination before, during and after CRT. The apparent diffusion coefficient (ADC), IVIM-derived parameters (D, f, and D*), and stretched-exponential model-derived parameters (DDC and α) were measured. The parameters and their corresponding changes during and after CRT were compared between pCR and non-pCR. Receiver-operating characteristic curve analysis was performed to evaluate the diagnostic performance. Coefficient of variations and intraclass correlation coefficient were calculated to assess reliability and agreement. RESULTS: Nineteen patients achieved pCR while 79 did not. The pCR group had higher ADC and α (ADC2 and α2 ), and their changes (ΔADC2 , and Δα2 ) at the endpoint than non-pCR group. α2 and ADC2 yielded similar AUCs (P = 0.339), Δα2 and ΔADC2 yielded similar AUCs (P = 0.263) ADC and α presented substantial agreement, and α presented the minimum CV (5.0-7.0%). CONCLUSION: ADC and α were useful for assessing pCR after CRT. α might be more useful because it demonstrated better diagnostic performance than IVIM-derived parameters and better reliability than ADC. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:175-183.

A simple and cost-saving phenotypic drug susceptibility testing of HIV-1.

It is essential to monitor the occurrence of drug-resistant strains and to provide guidance for clinically adapted antiviral treatment of HIV/AIDS. In this study, an individual patient's HIV-1 pol gene encoding the full length of protease and part of the reverse transcriptase was packaged into a modified lentivirus carrying dual-reporters ZsGreen and luciferase. The optimal coefficient of correlation between drug concentration and luciferase activity was optimized. A clear-cut dose-dependent relationship between lentivirus production and luciferase activity was found in the phenotypic testing system. Fold changes (FC) to a wild-type control HIV-1 strain ratios were determined reflecting the phenotypic susceptibility of treatment-exposed patient's HIV-1 strains to 12 HIV-1 inhibitors including 6 nucleoside reverse-transcriptase inhibitors (NRTIs), 4 non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 2 protease inhibitors (PIs). Phenotypic susceptibility calls from 8 HIV-1 infected patients were consistent with 80-90% genotypic evaluations, while phenotypic assessments rectified 10-20% genotypic resistance calls. By a half of replacement with ZsGreen reporter, the consumption of high cost Bright-Glo Luciferase Assay is reduced, making this assay cheaper when a large number of HIV-1 infected individuals are tested. The study provides a useful tool for interpreting meaningful genotypic mutations and guiding tailored antiviral treatment of HIV/AIDS in clinical practice.

A Modified Model for Assessment for Retreatment with Transarterial Chemoembolization in Chinese Hepatocellular Carcinoma Patients.

PURPOSE: To develop a modified assessment for retreatment with transarterial chemoembolization (mART) score that may be more suitable for Chinese patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Chinese patients with HCC who were treated with transarterial chemoembolization in four hospitals were included. A univariate analysis and a multivariate forward Cox regression analysis were used to identify significant prognostic factors of overall survival (OS). A point scoring model was subsequently developed from the training cohort, and the validation process was performed in the validation cohort. RESULTS: The study included 259 patients (124 patients in the training cohort and 135 patients in the validation cohort). Increase in Child-Pugh scores relative to the baseline (P < .001), Barcelona Clinic Liver Cancer (BCLC) stage B before first transarterial chemoembolization (P = .001), and absence of radiologic tumor response (P < .001) were identified as negative prognostic factors for OS and were used to create the mART scores. BCLC staging was substituted for aspartate aminotransferase increase in the mART scores. The mART scores differentiated two groups with distinct prognosis by a cutoff score of 2.5 points (22.9 mo [95% confidence interval (CI), 17.4-28.4] vs 8.9 mo [95% CI, 7.5-10.3] in median survival; P < .001). In the validation cohort, the C index in assessment for retreatment with transarterial chemoembolization (ART) criteria was 0.64, whereas it was 0.82 in mART criteria. CONCLUSIONS: In Chinese patients with HCC, mART score of > 2.5 before second transarterial chemoembolization was associated with poor prognosis. The mART score was probably better validated compared with the ART score.

ANVCFV Score System: Assessment for Probability of New Vertebral Compression Fractures after Percutaneous Vertebroplasty in Patients with Vertebral Compression Fractures.

BACKGROUND: Percutaneous vertebroplasty (PVP) is widely used for the treatment of painful vertebral compression fractures (VCFs). However, new VCFs occur frequently after PVP. OBJECTIVES: We aim to establish an objective risk score system to assess the possibility of new vertebral fractures in patients with VCFs undergoing PVP. STUDY DESIGN: This study was a retrospective study, and it was approved by the Institutional Review Board of our 2 institutions. SETTING: This study consists of patients from 2 large academic centers. METHODS: Patients with VCFs who underwent their first PVP and met the inclusion criteria between January 2007 and December 2013 at Hospital A (training cohort) and Hospital B (validation cohort) were included. In the training cohort, the independent risk factors for new VCFs after PVP were identified by multivariate stepwise backward Cox regression analysis from the risk factors selected by univariate analysis and Harrell's C-statistics and used to develop the score system (assessment for new VCFs after PVP [ANVCFV]) to predict the probability of new VCFs. RESULTS: In total, 397 patients (training cohort: n = 241; validation cohort: n = 156) were included in this study. In the training cohort, the ANVCFV score was developed based on 5 independent risk factors for the new VCFs after PVP, including lower computed tomography (CT) values, pre-existing old VCFs, intradiscal cement leakage, more than one vertebra treated, and superior or inferior marginal cement distribution in the vertebra. The patients were divided into 2 groups by the ANVCFV score of -1.5 to 8.5 vs. > 8.5 points in the probability of new VCFs (median fracture-free time: 1846 vs. 732 days; P < 0.001) in the training cohort. The accuracy of this score system was 77.4% for the training cohort and 85.3% for the validation cohort. LIMITATIONS: The main limitations of this study are that it is a retrospective study and that there is a significant difference of the treated vertebrae of PVP per session between the 2 cohorts. CONCLUSION: Patients who underwent their first PVP with an ANVCFV score > 8.5 points may exhibit an increased chance of suffering from new VCFs.

A stationary north-finding scheme for an azimuth rotational IMU utilizing a linear state equality constraint.

The Kalman filter (KF) has always been used to improve north-finding performance under practical conditions. By analyzing the characteristics of the azimuth rotational inertial measurement unit (ARIMU) on a stationary base, a linear state equality constraint for the conventional KF used in the fine north-finding filtering phase is derived. Then, a constrained KF using the state equality constraint is proposed and studied in depth. Estimation behaviors of the concerned navigation errors when implementing the conventional KF scheme and the constrained KF scheme during stationary north-finding are investigated analytically by the stochastic observability approach, which can provide explicit formulations of the navigation errors with influencing variables. Finally, multiple practical experimental tests at a fixed position are done on a postulate system to compare the stationary north-finding performance of the two filtering schemes. In conclusion, this study has successfully extended the utilization of the stochastic observability approach for analytic descriptions of estimation behaviors of the concerned navigation errors, and the constrained KF scheme has demonstrated its superiority over the conventional KF scheme for ARIMU stationary north-finding both theoretically and practically.

[Structure problem analysis and trend prediction of energy supply and demand in Guangzhou City].

This paper aims at the tense situation of energy demand and supply and analysis the current situation and problems of energy supply and demand in Guangzhou. We predict total demand of energy which will be 4534.7 x 10(4) of standard coal in 2010 by using the department analysis method and sequence method, and the balance between supply and demand of energy will be 45,000 thousand tons of standard coal. From the primary conclusions of our empirical analysis and together with the overall environment of energy in Guangdong and China, we think the development strategies of energy in Guangzhou in the future should involve several main points as following: (1) Energy of Guangzhou should base on the overall energy development programming of China and that is, it should depend on the "transmission of electricity from the western to the eastern region", power incorporation of Sanxia, power generated of water energy, nuclear power and new resource. (2) Stop setting up or expending the natural monopoly and resource oriented Huangpu thermal power plant located in the windward direction of summer of Guangzhou which has serious pollution and consumes large quantities of energy. (3) It should not absolutely depend on the coal of the poor mountainous region of Guangdong and small power station and can make full use of the resource potential.

[An event-related potential study the on information processing of binocular disparity in random-dot stereogram].

OBJECTIVE: To study the effects of discontinuous-continuous disparity gradient, uncrossed-crossed disparity and small-large disparity in random-dot stereogram (RDS) on the event-related potentials (ERPs). METHOD: Behavioral data and ERP were recorded when 16 healthy participants (8 males and 8 females) with normal depth perception were performing the task, in which the stereopsis were generated by red-blue glasses. RESULT: 1) The accuracy in discontinuous disparity gradient was higher than that in continuous disparity gradient, and the accuracy in large disparity was higher than that in small one. 2) Discontinuous disparity gradient elicited shorter N160 latency and larger N350 amplitude than continuous disparity gradient did. Compared with uncrossed disparity, crossed disparity elicited shorter N350 latency. In addition, large disparity elicited shorter N160 latency and larger P280 amplitude than small disparity did. CONCLUSION: The effect of disparity gradient on disparity information processing is significant, and the discontinuous disparity gradient has its processing advantage. Latency of N160 and amplitude of P280 is correlated with the information processing of the size of disparity. N350 component is correlated with the information processing of the uncrossed-crossed information of disparity.