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Agricultural nozzles are the main components that perform the spraying of agrochemicals, and their proper functionality is a key element for uniform spray application on crops. Because nozzles have small orifices, they can become clogged when there is debris from the agrochemical in the tank. Nozzle clogging during spray application results in poor pest and weed management and increased cost for re-spraying the affected crop row. Measures used to prevent nozzles from clogging include using screens or strainers to filter out debris before it reaches the nozzle tip, as well as performing regular checks on the nozzles. However, nozzle clogging still occurs during spraying despite the precautions taken. Thus, a device that can detect nozzle clogging during spraying is necessary to enable a quicker response that will ensure uniform application across each row of the crop. A novel, patented device for detecting clogged nozzles that is externally attachable to each nozzle on a sprayer boom was developed in the Precision Application Technology Lab at Arkansas State University. The main objective of this article is to present a general description of this prototype nozzle clog detection device and the nozzle clog detection system. Spray droplet size and pattern tests under controlled conditions and spray coverage tests under field conditions were conducted with and without the device to determine if there were significant differences in droplet size, spray pattern, or spray coverage between using and not using the device. The tests demonstrated that this new technology has potential for detecting clogged nozzles without significantly influencing spray quality for extended-range nozzles but not for ultra low-drift nozzles. To increase the reliability of the performance of this new technology, further improvements in the design need to be considered. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to gauge dentists' interest, knowledge and training in implantology, and to compare their treatment preferences with current literature. Subsequently, this information may be used to evaluate implantology education pathways.Methods: A cross-sectional postal survey of 600 randomly selected dentists registered with the Dental Practice Board of Victoria was conducted. Respondents were asked about background, interest and training in implantology, and implant treatment preferences. Results were analysed according to primary practice location, decade of graduation and attendance at continuing professional development (CPD) programmes.Results: One hundred and seventy-six questionnaires were included for analysis. In general, dentists rate their implant knowledge, interest and enjoyment in restoring implants favourably. No differences were found between city and country practitioners, and different graduation decades. The level of CPD significantly influenced treatment preferences. Practitioners were generally unwilling to treat patients taking bisphosphonates, or to perform grafting procedures. Most dentists provide common services to treat peri-implant conditions. Direct-to-fixture is the most popular fixture-abutment connection.Conclusions: Overall, there is a high level of implant knowledge corresponding to current evidence in the literature. Level of CPD attendance is the most important factor in dentists' willingness to provide more implant therapy options. [ABSTRACT FROM AUTHOR]

Thermal imaging is widely utilized in agricultural applications such as examining plant physiology, yield prediction, irrigation scheduling, bruises and pathogen determination in fruits and vegetables. There is a need for a cost effective thermal device for this wide range of applications. In this study, a low-cost prototype thermal device was used to measure the temperature of FFBs at three maturity levels, that are under-ripe, ripe and over-ripe. The experiment was repeated using a commercial thermal camera. Then, the mean temperature obtained from both the prototype and commercial thermal sensors was compared. Our results showed the prototype thermal device is capable of estimating the mean temperature of oil palm FFBs with the values analogous to the mean temperature from commercial thermal camera with R2 = 0.71. [ABSTRACT FROM AUTHOR]

The article examines the performance of a manual and remote-controlled sweet cherry harvesters. Topics mentioned include the performance of both equipment in terms of the accuracy of hitting a target branch, field of view for perceiving target branches, and ease of tree rows maneuvering, and the advantage of the remote operation of the harvester over manual operation for achieving higher rate of harvesting sweet cherries.

Fuel efficiency and pollution reduction relate closely to air-ratio (i.e. lambda) control among all the engine control variables. Lambda indicates the amount that the actual available air-fuel ratio mixture differs from the stoichiometric air-fuel ratio of the fuel being used. Accurate lambda prediction is essential for effective lambda control. This paper employs an emerging online time-sequence incremental algorithm and proposes one novel online time-sequence decremental algorithm based on least squares support vector machines (LS-SVMs) to continually update the built LS-SVM lambda function whenever a sample is added to, or removed from, the training dataset. Moreover, the online time-sequence algorithm can also significantly shorten the function updating time as compared with function retraining from scratch. In order to evaluate the effectiveness of this pair of online time-sequence algorithms, three lambda time series obtained from experiments under different operating conditions are employed. The prediction results of the online time-sequence algorithms over unseen cases are compared with those under classical LS-SVMs, typical decremental LS-SVMs, and neural networks. Experimental results show that the online time-sequence incremental and decremental LS-SVMs are superior to the other three typical methods. [ABSTRACT FROM AUTHOR]

This paper proposes a novel modelling and optimization approach for steady state and transient performance tune-up of an engine at idle speed. In terms of modelling, Latin hypercube sampling and multiple-input and multiple-output (MIMO) least-squares support vector machines (LS-SVMs) are proposed to build an engine idle-speed model based on experimental sample data. Then, a genetic algorithm (GA) and particle swarm optimization (PSO) are applied to obtain an optimal electronic control unit setting automatically, under various user-defined constraints. All of the above techniques mentioned are artificial intelligence techniques. To illustrate the advantages of the MIMO LS-SVM, a traditional multilayer feedforward neural network (MFN) is also applied to build the engine idle-speed model. The modelling accuracies of the MIMO LS-SVM and MFN are also compared. This study shows that the predicted results using the estimated model from the LS-SVM are in good agreement with the actual test results. Moreover, both the GA and PSO optimization results show an impressive improvement on idle-speed performance in a test engine. The optimization results also indicate that PSO is more efficient than the GA in an idle-speed control optimization problem based on the LS-SVM model. As the proposed methodology is generic, it can be applied to different engine modelling and control optimization problems. [ABSTRACT FROM AUTHOR]

Background: Neurology trials typically rely on composite scales for measuring symptom severity. Completing all items in a long scale can be burdensome for patients, caregivers, and trial personnel., Objectives: To test the hypothesis that sparse item testing, aided by item-response modelling, can preserve the power for detecting treatment effect in a controlled trial., Methods: UPDRS (Unified Parkinson's Disease Rating Scale) Part III (motor examinations) data from a placebo-controlled trial (N = 391) of ropinirole were analysed with a longitudinal item-response model. Symptom severity was estimated directly from item scores as a latent variable, without needing the total score. This enabled sparse item testing. With the symptom severity as a clinical endpoint, the potential power loss for detecting treatment effect due to the sparse testing was assessed by simulation., Results: When each patient took 18 of all 27 tests in UPDRS Part III at each study visit, there was no appreciable power loss. Reducing four visits to three also had negligible effects on power. A threefold reduction of the total tests that each patient needed to do throughout the trial, from 108 to 27, only compromised power slightly, e.g., from 92 to 87% at N = 160., Conclusions: These findings show that using the symptom severity derived from item scores as the endpoint allows sparse testing to drastically reduce trial burden without incurring major power loss. This benefit would multiply for indications like Alzheimer's disease where modern trials often require patients to be tested on multiple scales at several times., (© 2024. The Author(s).)

Background: This study provides a detailed analysis of the daily fluctuations in coronavirus disease 2019 (COVID-19) case numbers in London from January 31, 2020 to February 24, 2022. The primary objective was to enhance understanding of the interactions among government pandemic responses, viral mutations, and the subsequent changes in COVID-19 case incidences., Methods: We employed the adaptive Fourier decomposition (AFD) method to analyze diurnal changes and further segmented the AFD into novel multi-component groups consisting of one to three elements. These restructured components were rigorously evaluated using Pearson correlation, and their effectiveness was compared with other signal analysis techniques. This study introduced a novel approach to differentiate individual components across various time-frequency scales using basis decomposition methods., Results: Analysis of London's daily COVID-19 data using AFD revealed a strong correlation between the "stay at home" directive and high-frequency components during the first epidemic wave. This indicates the need for sustained implementation of vaccination policies to maintain their effectiveness., Discussion: The AFD component method provides a comprehensive analysis of the immediate and prolonged impact of governmental policies on the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This robust tool has proven invaluable for analyzing COVID-19 pandemic data, offering critical insights that guide the formulation of future preventive and public health strategies., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

These analyses characterized tofacitinib pharmacokinetics (PKs) in children and adolescents with juvenile idiopathic arthritis (JIA). Data were pooled from phase I (NCT01513902), phase III (NCT02592434), and open-label, long-term extension (NCT01500551) studies of tofacitinib tablet/solution (weight-based doses administered twice daily [b.i.d.]) in patients with JIA aged 2 to less than 18 years. Population PK modeling used a nonlinear mixed-effects approach, with covariates identified using stepwise forward-inclusion backward-deletion procedures. Simulations were performed to derive dosing recommendations for children and adolescents with JIA. Two hundred forty-six pediatric patients were included in the population PK model. A one-compartment model with first-order elimination and absorption with body weight as a covariate for oral clearance and apparent volume of distribution sufficiently described the data. Oral solution was associated with comparable average concentration (C avg ) and slightly higher (113.9%) maximum concentration (C max ) versus tablet, which was confirmed by a subsequent randomized, open-label, bioavailability study conducted in healthy adult participants (n = 12) by demonstrating adjusted geometric mean ratios (90% confidence interval) between oral solution and tablet of 1.04 (1.00-1.09) and 1.10 (1.00-1.21) for area under the curve extrapolated to infinity and C max , respectively (NCT04111614). A dosing regimen of 3.2 mg b.i.d. solution in patients 10 to less than 20 kg, 4 mg b.i.d. solution in patients 20 to less than 40 kg, and 5 mg b.i.d. tablet/solution in patients greater than or equal to 40 kg, irrespective of age, was proposed to achieve constant C avg across weight groups. In summary, population PK characterization informed a simplified tofacitinib dosing regimen that has been implemented in pediatric patients with JIA., (© 2024 Pfizer Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Pregnant women identified to carry hepatitis B surface antigen (HBsAg) should be linked to care for the determination of the need for long-term antiviral therapy (LTT). We assessed the performance of simplified criteria, free from HBV DNA quantification, to select women eligible for LTT using different international guidelines as a reference. A retrospective analysis of HBV-infected pregnant women enrolled in the phase 4 ANRS TA-PROHM study was conducted in Cambodia. Sensitivity, specificity, and AUROC were computed to compare three simplified criteria (TREAT-B, HBcrAg/ALT, and TA-PROHM) with the American (AASLD) and European (EASL) guidelines as a reference. An additional assessment was performed at 6 months postpartum. Of 651 HBsAg-positive women, 209 (32%) received peripartum antiviral prophylaxis using tenofovir disoproxil fumarate (TDF). During pregnancy, 9% and 12% of women were eligible for LTT according to AASLD and EASL guidelines, respectively; 21% and 24% of women were eligible for prophylactic TDF and 2% and 5% in those ineligible ( p < 0.001). Using the AASLD guidelines, the AUROC of TREAT-B, HBcrAg/ALT, and TA-PROHM scores were 0.88 (95%CI, 0.85-0.90), 0.90 (95%CI, 0.87-0.92), and 0.76 (95%CI, 0.73-0.80), respectively. Using the EASL guidelines, the AUROCs were lower: 0.73 (95%CI, 0.69-0.76), 0.76 (95%CI, 0.73-0.80), and 0.71 (95%CI, 0.67-0.74), respectively. Among those ineligible for prophylactic TDF, only 2% to 6% present an indication for LTT at 24 weeks postpartum. Few pregnant women are eligible for LTT, and the use of simplified criteria could represent an efficient triage option in decentralized areas to identify those negative for whom there is no urgent indication for LTT and focus on those positive for whom other exams must be conducted to confirm LTT indication.

Background: Fatigue can be a disabling multiple sclerosis (MS) symptom with no effective treatment options., Objective: Determine whether a low-fat diet improves fatigue in people with MS (PwMS)., Methods: We conducted a 16-week randomized controlled trial (RCT) and allocated PwMS to a low-fat diet (active, total daily fat calories not exceeding 20%) or wait-list (control) group. Subjects underwent 2 weeks of baseline diet data collection (24-hour diet recalls (24HDRs)), followed by randomization. The active group received 2 weeks of nutrition counseling and underwent a 12-week low-fat diet intervention. One set of three 24HDRs at baseline and week 16 were collected. We administered a food frequency questionnaire (FFQ) and Modified Fatigue Impact Scale (MFIS) every 4 weeks. The control group continued their pre-study diet and received diet training during the study completion., Results: We recruited 39 PwMS (20-active; 19-control). The active group decreased their daily caloric intake by 11% (95% confidence interval (CI): -18.5%, -3.0%) and the mean MFIS by 4.0 (95% CI: -12.0, 4.0) compared to the control (intent-to-treat). Sensitivity analysis strengthened the association with a mean MFIS difference of -13.9 (95% CI: -20.7, -7.2)., Conclusions: We demonstrated a significant reduction in fatigue with a low-fat dietary intervention in PwMS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is based on administration of vaccine and immunoglobulins (HBIg) to newborns at birth and maternal antiviral prophylaxis for those with an HBV-DNA viral load of at 5·3 log 10 IU/mL or more. Many low-income and middle-income countries face difficulty in accessing HBIg and HBV-DNA quantification. The aim of this study was to evaluate the effectiveness of an HBIg-free strategy to prevent MTCT of HBV., Methods: TA-PROHM was a single-arm, multicentre, phase 4 trial done in five maternity units in Cambodia. Pregnant women who were positive for hepatitis B surface antigen (HBsAg), aged 18 years or older were included. Women who were HCV or HIV positive, had creatinine clearance of less than 30 mL/min, severe gravid disease, and planned to give birth outside the study sites were excluded. From Oct 4, 2017, to Jan 9, 2019, HBsAg positive pregnant women who tested positive for hepatitis B e antigen (HBeAg) with a rapid diagnostic test were eligible to receive tenofovir disoproxil fumarate. From Jan 9, 2019, women who were HBeAg negative with an alanine aminotransferase concentration of ≥40 IU/L were also eligible to receive tenofovir disoproxil fumarate. Women in the tenofovir disoproxil fumarate eligible group received 300 mg of tenofovir disoproxil fumarate orally once a day from the 24th week of gestation until 6 weeks postpartum. The primary outcome was the overall proportion of infants who were HBsAg positive at 6 months of life, confirmed by positive HBV DNA quantification. For the primary outcome, the proportion (95% CI) of infants with HBsAg at 6 months was stratified according to infant's HBIg status, duration of maternal tenofovir disoproxil fumarate treatment (>4 weeks and ≤4 weeks), and study period (before and after the change in therapeutic algorithm) and was measured in a modified intention-to-treat analysis, which excluded infants lost to follow-up or who were withdrawn before 6 months. The study is registered with ClinicalTrials.gov, NCT02937779., Findings: From Oct 4, 2017, to Nov 27, 2020, 21 251 pregnant women were screened for HBsAg, of whom 1194 (6%) were enrolled in the study: 338 (28%) were eligible to receive tenofovir disoproxil fumarate. For the tenofovir disoproxil fumarate eligible group, four (1% [95% CI 0·34-3·20]) of 317 infants had HBV infection at 6 months; in the subgroup of 271 children who did not receive HBIg, four (1% [0·40-3·74]) had HBV infection at 6 months. In absence of HBIg, MTCT HBV transmission occurred in none (0% [0-1·61]) of 227 women who received tenofovir disoproxil fumarate for more than 4 weeks before giving birth and three (8% [1·75-22·47]) of 36 women who received tenofovir disoproxil fumarate for less than 4 weeks. In the tenofovir disoproxil fumarate ineligible group, seven (1% [0·40-2·02]) of 712 infants had HBV infection at 6 months; in the subgroup of 567 children who did not receive HBIg, six (1% [0·39-2·30]) had HBV infection at 6 months., Interpretation: An immunoglobulin-free strategy using an HBeAg rapid diagnosis test and alanine aminotransferase-based algorithm to assess eligibility for tenofovir, is effective at preventing MTCT of HBV when tenofovir was initiated at least 4 weeks before birth., Funding: French Agency for Research on AIDS and Viral Hepatitis and Emerging Infectious diseases., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

With the multiplication of electronic devices in our daily life, there is a need for tailored wideband electromagnetic (EM) absorbers that could be conformed on any type of surface-like antennas for interference attenuation or military vehicles for stealth applications. In this study, a wideband flexible flat electromagnetic absorber compatible with additive manufacturing has been studied in the X-Ku frequency bands. A multilayer structure has been optimized using a genetic algorithm (GA), adapting the restrictions of additive manufacturing and exploiting the EM properties of loaded and non-loaded filaments, of which the elaboration is described. After optimization, a bi-material multilayer absorber with a thickness of 4.1 mm has been designed to provide a reflectivity below -12 dB between 8 and 18 GHz. Finally, the designed multilayer structure was 3D-printed and measured in an anechoic chamber, achieving -11.8 dB between 7 and 18 GHz. Thus, the development of dedicated materials has demonstrated the strong potential of additive technologies for the manufacturing of thin wideband flexible EM absorbers.

Early clinical trials of therapies to treat Duchenne muscular dystrophy (DMD), a fatal genetic X-linked pediatric disease, have been designed based on the limited understanding of natural disease progression and variability in clinical measures over different stages of the continuum of the disease. The objective was to inform the design of DMD clinical trials by developing a disease progression model-based clinical trial simulation (CTS) platform based on measures commonly used in DMD trials. Data were integrated from past studies through the Duchenne Regulatory Science Consortium founded by the Critical Path Institute (15 clinical trials and studies, 1505 subjects, 27,252 observations). Using a nonlinear mixed-effects modeling approach, longitudinal dynamics of five measures were modeled (NorthStar Ambulatory Assessment, forced vital capacity, and the velocities of the following three timed functional tests: time to stand from supine, time to climb 4 stairs, and 10 meter walk-run time). The models were validated on external data sets and captured longitudinal changes in the five measures well, including both early disease when function improves as a result of growth and development and the decline in function in later stages. The models can be used in the CTS platform to perform trial simulations to optimize the selection of inclusion/exclusion criteria, selection of measures, and other trial parameters. The data sets and models have been reviewed by the US Food and Drug Administration and the European Medicines Agency; have been accepted into the Fit-for-Purpose and Qualification for Novel Methodologies pathways, respectively; and will be submitted for potential endorsement by both agencies., (© 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade., (© 2021. The Author(s).)

Introduction: ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) demonstrated the efficacy and safety of tafamidis in transthyretin amyloid cardiomyopathy (ATTR-CM). Model-based analyses from ATTR-ACT can examine predictor effects on dose-response/exposure-response relationships., Methods: Parametric hazard distributions were developed for all-cause mortality and frequency of cardiovascular-related hospitalization. Time-to-event models were fitted to survival data, and repeated time-to-event models were fitted to hospitalization data. Disease-specific characteristics were assessed as baseline predictors of event hazards., Results: There were 441 patients in this analysis. At month 30, 70.5% (tafamidis) and 57.1% (placebo) of patients were alive, with 154/441 deaths reported; 495 cardiovascular-related hospitalizations occurred. The cumulative risk of death was 42.1% (95% confidence interval [CI] 24.2-58.0) lower with tafamidis than with placebo, regardless of New York Heart Association (NYHA) class; significant predictors of decreased risk were genotype (wild-type), greater 6-Minute Walk Test (6MWT) distance, higher left ventricular ejection fraction (LVEF), and lower blood urea nitrogen (BUN) and N-terminal pro-B-type natriuretic peptide concentrations. The average cumulative risk of cardiovascular-related hospitalization up to 30 months was 40.8% (95% CI 31.0-49.7) lower with tafamidis in NYHA class I/II patients. Significant predictors of reduced risk were greater 6MWT distance, higher LVEF, and lower BUN and troponin I concentrations., Conclusions: Tafamidis reduced cumulative mortality and hospitalization risk versus placebo in patients with ATTR-CM. Baseline predictors of outcome were consistent with the cardiovascular nature of the disease and suggested that earlier treatment may improve outcomes. CLINICAL TRIALS., Gov Identifier: NCT01994889 (date of registration: November 26, 2013)., (© 2021. The Author(s).)

Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We characterized tofacitinib pharmacokinetics in patients with moderate to severe UC, and the effects of covariates on variability in pharmacokinetic parameter estimates. Data were pooled from 1 8-week phase 2 and 2 8-week phase 3 induction studies, and a 52-week phase 3 maintenance study (N = 1096). Population pharmacokinetic analysis was conducted using nonlinear mixed-effects modeling. Potential predictors of apparent oral clearance (CL/F) and volume of distribution (V/F) were evaluated. The PK was described by a 1-compartment model parameterized in terms of CL/F (26.3 L/hour [h]) and V/F (115.8 L), with first-order absorption (K a ; 9.85 h -1 ) and lag time (0.236 h). The derived elimination half-life was approximately 3.05 h. In the final model, baseline creatinine clearance, sex, and race (Asian vs non-Asian) were significant covariates for CL/F; significant covariates for V/F were age, sex, and body weight; baseline albumin and baseline Mayo score were not significant covariates. CL/F between-patient variability was estimated at 22%. Tofacitinib exposure did not change significantly over the duration of induction/maintenance treatment in patients with UC. Although statistically significant covariate effects on CL/F and V/F were observed, the magnitude of the effects are not clinically significant. Therefore, dose adjustment/restrictions for age, body weight, sex, race, or baseline disease severity are not required during tofacitinib treatment. ClinicalTrials.gov numbers: NCT00787202, NCT01465763, NCT01458951, NCT01458574., (© 2021 Pfizer Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: The paucity of hepatitis B virus (HBV) DNA measurement in low-/middle-income countries hinders the identification of HBV-infected pregnant women at risk of perinatal transmission. This study evaluates the validity of an algorithm selecting HBeAg-positive women and HBeAg-negative women with alanine aminotransferase (ALT) ≥40 IU/L as a predictor of high HBV DNA level., Methods: All women with reactive samples for hepatitis B surface antigen (HBsAg) were assessed with an SD BIOLINE HBeAg rapid test and HBV DNA quantification was performed. Validities of HBeAg and of the algorithm to identify HBV DNA >2 thresholds (5.3 and 7.3 log10 IU/mL) were evaluated., Results: For the 515 HBsAg-positive women, median age was 29 years, 92 (17.9%) were HBeAg positive, 47 (9.1%) were HBeAg negative with ALT ≥40 IU/L, and 144 (28.0%) had an HBV DNA >5.3 log10 IU/mL. Sensitivity and specificity of HBeAg were 61.8% and 99.2% for HBV DNA >5.3 log10 IU/mL and 81.3% and 96.7% for HBV DNA >7.3 log10 IU/mL. For the algorithm, sensitivity and specificity were 79.2% and 93.3% for HBV DNA level >5.3 log10 IU/mL and 92.7% and 88.1% for HBV DNA >7.3 log10 IU/mL. The AUCs for the algorithm (0.92 and 0.94 for HBV DNA >5.3 and 7.3, respectively) were significantly greater (P < .001) than the AUCs for HBeAg (0.81 and 0.89 for HBV DNA >5.3 and 7.3, respectively)., Conclusions: An algorithm using HBeAg and ALT level could be an effective strategy to identify HBV-infected pregnant women at risk of perinatal transmission in countries where HBV DNA quantification is not routinely available., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background & Aims: Renal toxicity of first generation protease inhibitors (PIs) was not a safety signal in phase III clinical trials, but was recently reported in recent studies. It appeared important to determine the clinical significance of these findings., Methods: We retrospectively analysed 101 HCV patients receiving triple therapy with telaprevir (n = 36) or boceprevir (n = 26) or double therapy (n = 39) with peginterferon and ribavirin and having a close monitoring of eGFR (MDRD formula) during and after treatment. EGFR decline over time was assessed by a linear mixed-effects model (LMEM) with search for possible explanatory covariates., Results: Patients treated with telaprevir presented a significant decrease of eGFR with the same kinetics: initial decrease at W (week) 4, nadir at W8 (mean decrease 17.0 ± 18.9 ml/min/1.73 m(2)) and return to baseline at W16. The W8 eGFR was correlated with the D0 eGFR (R(2) = 0.49). The LMEM showed that interindividual variability in the slope of eGFR vs time between D0 and W8 was non-significant and eGFR nadir could be predicted from eGFR obtained at D0. In multivariate analysis, eGFR intercept (i.e. baseline value) was associated with older age and male sex., Conclusion: The eGFR significantly varied in telaprevir group only. Our model showed that eGFR nadir mainly depended on initial eGFR. As telaprevir has been shown to inhibit mostly the drug transporter OCT2 which interacts with creatinine transport, the early decrease of eGFR observed could be a benign phenomenon. However, as unpredictable true renal toxicity may occur during therapy, we recommend a thorough follow-up of eGFR., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Efficient power calculation methods have previously been suggested for Wald test-based inference in mixed-effects models but the only available alternative for Likelihood ratio test-based hypothesis testing has been to perform computer-intensive multiple simulations and re-estimations. The proposed Monte Carlo Mapped Power (MCMP) method is based on the use of the difference in individual objective function values (ΔiOFV) derived from a large dataset simulated from a full model and subsequently re-estimated with the full and reduced models. The ΔiOFV is sampled and summed (∑ΔiOFVs) for each study at each sample size of interest to study, and the percentage of ∑ΔiOFVs greater than the significance criterion is taken as the power. The power versus sample size relationship established via the MCMP method was compared to traditional assessment of model-based power for six different pharmacokinetic and pharmacodynamic models and designs. In each case, 1,000 simulated datasets were analysed with the full and reduced models. There was concordance in power between the traditional and MCMP methods such that for 90% power, the difference in required sample size was in most investigated cases less than 10%. The MCMP method was able to provide relevant power information for a representative pharmacometric model at less than 1% of the run-time of an SSE. The suggested MCMP method provides a fast and accurate prediction of the power and sample size relationship.