Labeling For Use Research Articles

Zoysia spp. putting green tolerance to postemergence herbicides

AbstractSpecies of Zoysia Willd. are used on approximately 9550 ha of golf course surfaces throughout the United States, primarily fairways and tees in transitional climates. Recently, cultivars featuring dwarf canopy height and improved quality have been released for putting green use; however, tolerance of these cultivars to postemergence herbicides is unknown. Field research was conducted in 2021 and 2022 evaluating the tolerance of Prizm® [Zoysia matrella (L.) Merr.] and Lazer® [Z. matrella (L.) Merr. × Zoysia minima (Colenso) Zotov] zoysiagrass to pyrimisulfan + penoxsulam (Aethon™), pyrimisulfan (Arkon™), flazasulfuron (Katana®), 2,4‐D + quinclorac + dicamba + sulfentrazone (Q4® Plus), 2,4‐D + MCPP + dicamba + carfentrazone (SpeedZone® EW), 2,4‐D + MCPP + dicamba + sulfentrazone (Surge®), and pyrimisulfan (formulated as a granule; Vexis®). A nontreated check was included for comparison. All of these herbicides have commercial labeling for use on zoysiagrass (Zoysia Willd.); however, none of these herbicides have labeling for use on zoysiagrass putting greens. Application rates in this study exceeded label maximums (for use on zoysiagrass) to ascertain the upper limits of Prizm® and Lazer® tolerance to these herbicides in Knoxville, TN and College Station, TX, respectively. Plots were arranged in randomized complete block design with four replications at both sites. Turfgrass injury was visually evaluated with data subjected to analysis of variance. Prizm® in Tennessee exhibited commercially acceptable tolerance to the applied herbicides, resulting in ≤8% injury either year. Lazer® in Texas sustained injury ranging from 21% to 61% and 10% to 31% in 2021 and 2022, respectively. Conditions of extreme heat and drought in Texas may have exacerbated differences in Lazer® tolerance to applied herbicides between years. Additional research across varying geographies and environmental conditions is needed to better understand tolerance of new zoysiagrass putting green lines, particularly within Z. minima.

Oxyfluorfen use in Combination with Clomazone or Quinclorac

Abstract Oxyfluorfen, a Herbicide Resistance Action Committee (HRAC)/Weed Science Society of America (WSSA) Group 14 herbicide that inhibits protoporphyrinogen IX oxidase, has shown significant potential in controlling barnyardgrass. Despite its current lack of labeling for use in midsouthern U.S. rice due to the potential for crop injury, the introduction of a trait in rice that confers resistance to oxyfluorfen could provide producers with an effective alternative site of action for weed control. Field experiments were conducted during the 2021 and 2022 growing seasons near Stuttgart, AR, and near Lonoke, AR, to determine the optimum rates of clomazone (280 or 336 g ha-1) and oxyfluorfen (673 or 840 g ha-1) to use in sequential preemergence (PRE) and postemergence (POST) applications on a silt loam soil and to assess the efficacy of oxyfluorfen when combined with clomazone and quinclorac PRE, followed by oxyfluorfen POST. No differences in barnyardgrass control were observed among treatments 14 days after emergence (DAE) in three site years, as all control was ≥90%. By 35 days after the postemergence application (DAPOST), all barnyardgrass control was ≥94% for herbicide treatments in all site years. All herbicide treatments resulted in lower barnyardgrass seed production than the nontreated in 2021. Contrasts revealed that oxyfluorfen applied PRE on a silt loam soil resulting in barnyardgrass control similar to clomazone or quinclorac alone at 14 DAE. Although oxyfluorfen combined with clomazone or quinclorac did not increase barnyardgrass control, an additional site of action for control of this weed could help reduce the evolution of resistance. Mixing oxyfluorfen with clomazone in a dry-seeded rice production system in the midsouthern U.S. would effectively control barnyardgrass and reduce the risk for resistance to both herbicides, further highlighting the potential of oxyfluorfen in rice production.

Large-Scale Land Cover Mapping Framework Based on Prior Product Label Generation: A Case Study of Cambodia

Large-Scale land cover mapping (LLCM) based on deep learning models necessitates a substantial number of high-precision sample datasets. However, the limited availability of such datasets poses challenges in regularly updating land cover products. A commonly referenced method involves utilizing prior products (PPs) as labels to achieve up-to-date land cover mapping. Nonetheless, the accuracy of PPs at the regional level remains uncertain, and the Remote Sensing Image (RSI) corresponding to the product is not publicly accessible. Consequently, the sample dataset constructed through geographic location matching may lack precision. Errors in such datasets are not only due to inherent product discrepancies, and can also arise from temporal and scale disparities between the RSI and PPs. In order to solve the above problems, this paper proposes an LLCM framework for generating labels for use with PPs. The framework consists of three main parts. First, initial generation of labels, in which the collected PPs are integrated based on D-S evidence theory and initial labels are obtained using the generated trust map. Second, for dynamic label correction, a two-stage training method based on initial labels is adopted. The correction model is pretrained in the first stage, then the confidence probability (CP) correction module of the dynamic threshold value and NDVI correction module are introduced in the second stage. The initial labels are iteratively corrected while the model is trained using the joint correction loss, with the corrected labels obtained after training. Finally, the classification model is trained using the corrected labels. Using the proposed land cover mapping framework, this study used PPs to produce a 10 m spatial resolution land cover map of Cambodia in 2020. The overall accuracy of the land cover map was 91.68% and the Kappa value was 0.8808. Based on these results, the proposed mapping framework can effectively use PPs to update medium-resolution large-scale land cover datasets, and provides a powerful solution for label acquisition in LLCM projects.

Development of xanthan gum intelligent oil-in-water ink and its application in pork freshness preservation

To optimize the stability of oil-based inks and ensure their wide application in freshness indication, new natural indicator inks were prepared using a stable oil-in-water structure. This study selected natural Lycium ruthenicum anthocyanin as the dye and glucose as the pigment carrier. Soybean oil was introduced as a linker and xanthan gum as a thickener, and an oil-in-water ink with the function of freshness indication was successfully developed. In ensuring the safety of ink labels for use on food packaging, particular attention is paid to the origin and properties of the materials used. All ingredients are of food-grade or bio-friendly provenance, thereby ensuring the safety of the product when in direct contact with food. We measured the viscosity, particle size and fineness of the ink for micro characterization and evaluated its macro printing performance by its printing effect on A4 paper. According to the experimental results, when the water-oil ratio of the ink is 10:5, the average particle size of the emulsion system is 822.83 nm, and the fineness reaches 5 μm. These values are relatively low, which indicates that the stability of the ink system is high at this time, and the ink shows excellent rheological and printing characteristics. With this water-to-oil ratio, the ink can show the best results when printed on A4 paper, clearly displaying image details. In addition, in fresh pork applications, inks with a 10: 5 water-to-oil ratio provide an accurate and highly sensitive indication of the freshness of pork. When the freshness of the pork changes, the ink color responds promptly. This high sensitivity makes the ink ideal for use as a food freshness indication tool, providing consumers with an intuitive and reliable reference for pork freshness. As a further innovation, combining this ink-printed label with a WeChat app not only allows consumers to know the freshness of the food in real-time but also tracks the supply chain information of the food, providing a more comprehensive application prospect for freshness-indicating products.

Development of multifunctional curcuminoid dye-based inks and applications

Curcuminoids are a group of naturally occurring polyphenolic compounds found in turmeric (Curcuma longa) that are widely employed as coloring agents in traditional medicine and the food industry. Moreover, they have been used as dyes in pH indicators, which are part of diagnostic intelligent packaging. Recently, there has seen a steady increase of the interest in the curcuminoids due to their fluorescent property. In this study, a curcuminoid dye (CurD) containing a total curcuminoid content of 38.34 ± 0.66 % w/w was prepared by using a microwave-assisted extraction, and was used as a multifunctional dye with different commercial screen binders, including solvent-based ink (Si) and water-based ink (Wi). A solution of CurD (0.1 % w/v) exhibited a maximum fluorescence wavelength of 526 nm. Based on the print-quality test using a screen printing on clear polyvinyl chloride and paper, the viscosity and drying time of CurD-Si and CurD-Wi inks were not significantly different. The printed-inks had a yellow color under illuminant D50 and D65, and exhibited remarkable green fluorescence under UVA (365 nm). The total color differences (∆Eab∗), which are not fluorescence intensities, of both inks were changed by increasing CurD concentrations. CurD-Wi containing 1 % w/w CurD could be printed as latent graphics on a paper label for use as an anti-counterfeiting application. In addition, it immediately responded to alkaline solution and vapor through color transition from yellow to orange-brown, with the maximum ∆Eab∗ values of 15.02 and 26.62, respectively. In contrast, all CurD-Si samples could fluoresce but did not respond to alkaline conditions.

Analyzing astronomical data with machine learning techniques

Classification is a popular task in the field of machine learning (ML) and artificial intelligence (AI), and it happens when outputs are categorical variables. There are a wide variety of models that attempt to draw some conclusions from observed values, so classification algorithms predict categorical class labels for use in classifying new data. Popular classification models including logistic regression, decision tree, random forest, support vector machine (SVM), multilayer perceptron, naive bayes, neural networks have proven to be efficient and accurate applied to many industrial and scientific problems. Particularly, application of ML to astronomy has shown to be very useful for classification, clustering and data cleaning. It is because after learning computers, these tasks can be done automatically by them in a more precise and more rapid way than human operators. In view of this, in this paper, we will review some of these popular classification algorithms, and then we apply some of them to the observational data of nonvariable and the RR Lyrae variable stars that come from the SDSS survey. For the sake of comparison, we calculate the accuracy and $F1$-score of the applied models.

Understanding and addressing food waste from confusion in date labeling using a stakeholders’ survey

Food waste is a significant global challenge for the humanity and environment. Different agencies world-wide are trying to reduce food waste in several ways. Of the reasons behind food waste, consumer level waste is significant, often hard to track, but can be a very critical contributor to food security if prevented. Food waste due to confusion in date labeling is one such way that consumers waste food. Currently, there are about 50 different types of date labels in use in the United States of America (USA) and they are not regulated. Due to the complex nature of consumer level food waste, our multi-disciplinary team of researchers conducted a stakeholder needs assessment survey (n = 123) to better understand the existing confusion over date labels. Our survey results indicate that majority of the stakeholders (75% of responses received in this category) are confused about the date labeling and associate it with food safety and feel unsafe to consume foods beyond the date indicated on the labels. The stakeholders think that better understanding the science behind such date labels and potential application of modern technology such as a mobile phone app, targeted community outreach education, social media, and print materials may help reduce food waste, which in turn would positively contribute to global food security. • A stakeholders' survey was conducted in the farm-to-fork continuum. • Respondents confuse date labels with food safety. • A multi-disciplinary approach, novel use-inspired technology, and community level intervention are key to reduce food waste.

Children With Enthesitis-Related Arthritis and Possible Benefits From Treatments for Adults With Spondyloarthritis.

This review will summarize clinical, genetic, and pathophysiologic characteristics that are shared between children with enthesitis-related arthritis (ERA) with axial involvement and adults with nonradiographic (and in some cases radiographic) axial spondyloarthritis (SpA), as well as between children with ERA and primarily peripheral disease manifestations and adults with peripheral SpA. Due to the differences in classification criteria for children with ERA and adults with axial and peripheral SpA, the US Food and Drug Administration (FDA) granted automatic full waivers of studies in children for new medications for "axial spondyloarthropathies including ankylosing spondylitis" up until July 2020. Thus, although current juvenile idiopathic arthritis treatment guidelines recommend the use of biologic disease-modifying antirheumatic drugs as part of the early treatment for patients with ERA, none of the FDA-approved therapies for peripheral SpA or nonradiographic axial SpA (certolizumab pegol, ixekizumab, and secukinumab) have been studied or are labeled for use in children with ERA. Considering the similarities between adult SpA and ERA in terms of etiology, genetics, pathogenesis, and clinical manifestations summarized in this review, medications approved for axial SpA or peripheral SpA should also be studied in children with active ERA involving axial or peripheral joints, respectively, with the intent to achieve labeling for use in children. Considering the current lack of effective FDA-approved therapies for ERA, the FDA should also consider requiring pediatric studies for medications that have already been approved for the treatment of adults with SpA.

A radical approach to radicals.

Nitroxide radicals are characterized by a long-lived spin-unpaired electronic ground state and are strongly sensitive to their chemical surroundings. Combined with electron paramagnetic resonance spectroscopy, these electronic features have led to the widespread application of nitroxide derivatives as spin labels for use in studying protein structure and dynamics. Site-directed spin labelling requires the incorporation of nitroxides into the protein structure, leading to a new protein-ligand molecular model. However, in protein crystallographic refinement nitroxides are highly unusual molecules with an atypical chemical composition. Because macromolecular crystallography is almost entirely agnostic to chemical radicals, their structural information is generally less accurate or even erroneous. In this work, proteins that contain an example of a radical compound (Chemical Component Dictionary ID MTN) from the nitroxide family were re-refined by defining its ideal structural parameters based on quantum-chemical calculations. The refinement results show that this procedure improves the MTN ligand geometries, while at the same time retaining higher agreement with experimental data.

G6PD distribution in sub-Saharan Africa and potential risks of using chloroquine/hydroxychloroquine based treatments for COVID-19

Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, p = 2.4 × 10−3). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydroxychloroquine for treatment of COVID-19 in Africans.

Breeding and Evaluation of Fine Fescues for Increased Tolerance to Mesotrione Herbicide

Fine fescues (Festuca sp.) are a group of species that require fewer inputs, such as fertilizer, than other cool-season species managed for turf. They are adapted to infertile, acidic soils; shade; and drought. One area that poses additional challenges is the lack of weed control options for fine fescues during establishment from seed. Mesotrione is a herbicide that provides preemergence control of many broadleaf and grassy weeds, such as annual bluegrass (Poa annua), but is currently not labeled for use in fine fescues at seeding. The objectives of this research were 1) to use a recurrent selection technique to develop mesotrione-tolerant chewings fescue (Festuca rubra ssp. commutata), hard fescue (Festuca brevipila), and strong creeping red fescue (F. rubra spp. rubra); and 2) to conduct field trials to compare the new selections to commercially available cultivars and experimental lines not selected for tolerance to mesotrione. Progress was made after each of the three generations of recurrent selection. The top statistical grouping of entries for injury following application of mesotrione at the 8-oz/acre rate included all the third-generation (G3) hard fescues, all the G3 chewings fescues, and the G3 strong creeping red fescue STB1 Composite. After three generations, selections of hard, chewings, and strong creeping red fescues had equivalent or better tolerance to mesotrione than tall fescue (Festuca arundinacea) and kentucky bluegrass (Poa pratensis) cultivars, which are on the label for safe use at seeding. These new selections would provide turf managers an option to control weeds using mesotrione during seedling establishment of fine fescues.

Comparing lifeact and phalloidin for super-resolution imaging of actin in fixed cells.

Visualizing actin filaments in fixed cells is of great interest for a variety of topics in cell biology such as cell division, cell movement, and cell signaling. We investigated the possibility of replacing phalloidin, the standard reagent for super-resolution imaging of F-actin in fixed cells, with the actin binding peptide ‘lifeact’. We compared the labels for use in single molecule based super-resolution microscopy, where AlexaFluor 647 labeled phalloidin was used in a dSTORM modality and Atto 655 labeled lifeact was used in a single molecule imaging, reversible binding modality. We found that imaging with lifeact had a comparable resolution in reconstructed images and provided several advantages over phalloidin including lower costs, the ability to image multiple regions of interest on a coverslip without degradation, simplified sequential super-resolution imaging, and more continuous labeling of thin filaments.

What is at stake in the information sphere? Anxieties about malign information influence among ordinary Swedes

ABSTRACT Scholars, states and organisations have warned that authoritarian regimes and other hostile actors are projecting information to inflict harm upon others. Yet, there is little agreement on the nature of this threat. This is mirrored in the plethora of labels in use, ranging from “disinformation” to “sharp power” and “information warfare”. In order to investigate this menace further, we turn our focus to ordinary people’s anxieties, since a better understanding of threat perceptions will also provide a better understanding of the problem. We conducted a comprehensive case study comprising focus group discussions (n: 97) and an extensive survey (n: 2046) among Swedish citizens. We asked: To what extent do people worry about information influence and why? What can this tell us about the nature of this problem or threat? The empirical results suggest that respondents were first and foremost worried about societal cohesion and democracy. They also identified a risk that information influence can undermine trust in societal institutions and the EU. Based on our findings, we suggest that “malign information influence” is an appropriate label to be used in future research. Finally, we propose directions for future systematic research on how malign information infuence is received and processed in different national contexts.

ISUOG Safety Committee Position Statement on safe performance of obstetric and gynecological scans and equipment cleaning in context of COVID-19.

ISUOG Safety Committee Position Statement on safe performance of obstetric and gynecological scans and equipment cleaning in context of COVID-19.

Labels for Eternity: Testing Printed Labels for use in Wet Collections

Abstract Will printed labels survive prolonged immersion in collection fluids, and, if so, which printing system is preferable: inkjet, laser, or thermal transfer printing? In a world with a wide variety of printers, printing substrates, and printer technologies, the interactions between them very likely affect long-term label preservation in the chemical environment of the preservation fluid. In fluid-preserved collections, the main issues frequently encountered with labels include delamination, abrasion, fading, and disintegration during immersion in solutions such as ethanol and formaldehyde aqueous solution (widely known under the commercial name formalin). Very few publications have presented testing procedures assessing the behavior and stability of printed matter immersed in the types of solvents used in fluid-based collections. This article presents a series of experiments set up at the National Natural History Collections at the Hebrew University of Jerusalem to test a variety of museum labels. The tests compared labels actually used in different natural history collections and included labels from both thermal transfer and inkjet printers. All were subjected to accelerated aging and mechanical abrasion. In our series of tests, inkjet labels gave the best performance.

Colloidal silver-based lateral flow immunoassay for rapid detection of melamine in milk and animal feed

An immunosilver chromatographic strip based on a monoclonal antibody was developed for the detection of melamine (MEL) residues in milk and animal feed. Colloidal silver nanoparticles (AgNPs), of a diameter of approximately 10.4 nm, were surface-modified with trisodium citrate dehydrate (TSC) in order to improve their stability and dispersion. The anti-MEL monoclonal antibody (mAb) was successfully immobilized on the surface of AgNPs by ionic interactions and characterized using XRD, UV–Vis, TEM and XPS analyses. Surface modification of Ag-mAb conjugates with varying cross-reactivity and thermo-stability was employed to design and prepare labels for use in a lateral flow immunoassay (LFIA) to examine whether these factors affect the performance of the assay. The results showed that no cross-reactions with homologues cyanuric acid, ammeline or ammelide were found, and the test strip remained stable after storage for one year at room temperature. Under optimized conditions, a detection limit of 0.30 ppm for standard melamine was achieved, and limits of detection of 0.750 ppm and 0.875 ppm were obtained in milk and animal feed, respectively.

Magnetic Nanoparticle-Based Lateral Flow Immunochromatographic Strip as a Reporter for Rapid Detection of Melamine.

Magnetite nanoparticles (MNPs) Fe3O4 and r-Fe2O3 were surface-modified with poly(ethylene glycol) (PEG) in order to improve their specificity and bioactivity. PEG and the anti-MEL monoclonal antibody (mAb) were successfully immobilized on the surface of MNPs and characterized using FTIR, UV-Vis and TEM analyses. Surface modification of MNPs-PEG-mAb conjugates of a variety of sizes and magnetite types was employed to design and prepare labels for use in a lateral flow immunoassay (LFIA) to test whether the size of the conjugate can affect the performance of the assay. The results showed that the detection limit was mainly determined by the size of the MNPs-PEG-mAb conjugate. Under optimized conditions, a detection limit of 0.4 ppm for melamine was achieved using Fe2O3-PEG-mAb, which was almost 5-fold lower than that of the Fe3O4-PEG-mAb conjugate (2.2 ppm).

Texture-modified foods and thickened fluids used in dysphagia: Israeli standardised terminology and definitions.

Texture-modified foods and thickened fluids are used as a strategy that aims to compensate for dysphagia and improve the safety and efficiency of swallowing. Currently, in Israel, there are no standardised terminologies and definitions for texture-modified diets. The inconsistent terminology adversely affects patient safety and the efficiency of communication between staff members both within and between health institutions. This present study describes a project of the Israeli Ministry of Health in which the labels and definitions of prevalent foods and fluids used in health institutions are mapped to develop a consensus on national standards. A multidisciplinary committee of speech-language pathologists (SLPs) and registered dietitians (RDs) was appointed. A questionnaire was developed to identify the labels of texture-modified foods and fluids used in the Israeli healthcare system. The questionnaire included questions on knowledge, attitudes and barriers related to the need for a consistent national terminology for texture-modified diets. Questionnaires were sent to 120 institutions. The project was conducted between September 2016 and December 2017. Twenty-six SLPs and 42 RDs responded. The answers revealed that there were 50 labels in use for texture-modified foods. When asked to describe the texture of a particular food item, up to 17 different labels were used. There was broad support for a standardised terminology. The results of the present study confirm the lack of national standards in clinical practice and the need for a consistent terminology. A consensus was achieved between the committee members and the committee adopted the International Dysphagia Diet Standardization Initiative (IDDSI) recommendations and adapted the terminology to Hebrew.

Photocatalyst activity indicating adhesive labels for use in the field

The preparation and characterisation of a resazurin-based photocatalyst activity indicator label is described. The label is applied to a number of different TiO2-based, photocatalytic materials, including self-cleaning: glass, tile, paint and awning materials, as well as a thin, sol-gel film, produced in-house. In all cases, the label exhibited a blue to pink colour transition upon irradiation with UV light. In most cases, the time taken to bleach 90% of the red component of the digital image of the ink, ttb(90), was twice that for a traditional Rz ink, produced by the drawdown method, since the former was twice as thick. Although not as fast as a drawdown Rz ink, by a factor of ca. Two, it still only takes minutes to change and the Rz label is much more easily used, stored and does not need the sample to be: very smooth, horizontal or flat. As such it appears ideal for testing samples, both quantitatively and qualitatively in situ, i.e. in the field.

Development of Guanfacine Extended-Release Dosing Strategies in Children and Adolescents with ADHD Using a Physiologically Based Pharmacokinetic Model to Predict Drug-Drug Interactions with Moderate CYP3A4 Inhibitors or Inducers.

BackgroundGuanfacine extended-release (GXR) is an orally administered, non-stimulant treatment for children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and is primarily metabolized by the 3A4 isozyme of cytochrome P450 (CYP3A4). The results of clinical pharmacokinetic (PK) studies indicate that guanfacine is sensitive to drug–drug interactions (DDIs) perpetrated by strong inhibitors and inducers of CYP3A4.ObjectiveThe aim was to provide guidance on the possible requirement for GXR dose adjustment in children and adolescents with ADHD by predicting DDIs following co-administration with moderate CYP3A4 inhibitors and inducers.MethodsA physiologically based PK model for GXR orally administered to healthy adults was developed based on physicochemical, in vitro and clinical PK data. The model was validated using clinical PK data for co-administration of GXR with ketoconazole (strong CYP3A4 inhibitor) or rifampicin (strong CYP3A4 inducer).ResultsModel predictions indicated that co-administration of GXR with the moderate CYP3A4 inhibitors erythromycin 500 mg three times a day or fluconazole 200 mg daily (q.d.) increased the guanfacine area under the plasma concentration–time curve (AUC) by 2.31-fold or 1.98-fold, respectively, compared with GXR monotherapy. The moderate CYP3A4 inducer efavirenz 400 mg or 600 mg q.d. was predicted to reduce guanfacine AUC to 58 or 33% of its value for GXR monotherapy, respectively.ConclusionWithout the requirement for additional clinical studies, the following GXR dose recommendations were developed and approved for US labeling for use in children and adolescents with ADHD: (1) decrease GXR to 50% of the usual target dose when it is co-administered with strong or moderate CYP3A4 inhibitors; (2) consider titrating GXR up to double the usual target dose over 1–2 weeks when it is co-administered with strong or moderate CYP3A4 inducers.