The HEXACO Personality Space Before and After Re-Rotation to Approximate the Big Five Dimensions.

We re-oriented the HEXACO personality dimensions to approximate the Big Five, using two measures of the Big Five as targets in a derivation sample and then in cross-validation samples. The HEXACO approximations of Big Five Agreeableness represented blends of HEXACO Agreeableness, Emotionality, and Honesty-Humility. The HEXACO approximations of Big Five Neuroticism represented blends of Emotionality with low Agreeableness and low Extraversion. The residual sixth dimension, unrelated to the Big Five, contrasted Honesty-Humility with HEXACO Agreeableness. We then examined, in additional samples, some correlates of the original and re-rotated HEXACO dimensions. In the original HEXACO factor space, Honesty-Humility was the strongest correlate of unethical behaviors (selfishness and cheating), participant age, and "assumed similarity" to a friend or partner. Upon re-rotation of the HEXACO factors, associations involving these variables were divided between Big Five Agreeableness and the residual sixth dimension. Sex differences were mainly associated with Emotionality but after re-rotation of the HEXACO factors were divided between Big Five Agreeableness and Neuroticism. We discuss the relative merits of the original and Big Five-targeted HEXACO dimensions with reference to the practical utility of Big Five Agreeableness and Neuroticism and the simplicity and theoretical interpretability of the original HEXACO factors.

N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an in vitro investigation.

N, N-dimethyltryptamine (DMT) is a psychedelic compound that has shown potential in the treatment of depression. Aside from the primary role of monoamine oxidase A (MAO-A) in DMT metabolism, the metabolic pathways are poorly understood. Increasing this understanding is an essential aspect of ensuring safe and efficacious use of DMT.This work aimed to investigate the cytochrome 450 (CYP) mediated metabolism of DMT by incubating DMT with recombinant human CYP enzymes and human liver microsomes (HLM) followed by analysis using high-resolution mass spectrometry for metabolite identification.DMT was rapidly metabolised by CYP2D6, while stable with all other investigated CYP enzymes. The metabolism of DMT in HLM was reduced after inclusion of harmine and SKF-525A whereas quinidine did not affect the metabolic rate, likely due to MAO-A residues present in HLM. Analysis of the CYP2D6 incubates showed formation of mono-, di- and tri-oxygenated metabolites, likely as a result of hydroxylation on the indole core.More research is needed to investigate the role of this metabolic pathway in vivo and any pharmacological activity of the proposed metabolites. Our findings may impact on safety issues following intake of ayahuasca in slow CYP2D6 metabolizers or with concomitant use of CYP2D6 inhibitors.

Effects of Enzyme Induction and Polymorphism on the Pharmacokinetics of Isoniazid and Rifampin in Tuberculosis/HIV Patients.

Tuberculosis is the most common cause of death in HIV-infected individuals. Rifampin and isoniazid are the backbones of the current first-line antitubercular therapy. The aim of the present study was to describe the time-dependent pharmacokinetics and pharmacogenetics of rifampin and isoniazid and to quantitatively evaluate the drug-drug interaction between rifampin and isoniazid in patients coinfected with HIV. Plasma concentrations of isoniazid, acetyl-isoniazid, isonicotinic acid, rifampin, and 25-desacetylrifampin from 40 HIV therapy-naive patients were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after the first dose and at steady state of antitubercular therapy. Patients were genotyped for determination of acetylator status and CYP2C19 phenotype. Nonlinear mixed-effects models were developed to describe the pharmacokinetic data. The model estimated an autoinduction of both rifampin bioavailability (0.5-fold) and clearance (2.3-fold). 25-Desacetylrifampin clearance was 2.1-fold higher at steady state than after the first dose. Additionally, ultrarapid CYP2C19 metabolizers had a 2-fold-higher rifampin clearance at steady state than intermediate or extensive metabolizers. An induction of isonicotinic acid formation from isoniazid dependent on total rifampin dose was estimated. Simulations indicated a 30% lower isoniazid exposure at steady state during administration of standard rifampin doses than isoniazid exposure in noninduced individuals. Rifampin exposure was correlated with CYP2C19 polymorphism, and rifampin administration may increase exposure to toxic metabolites by isoniazid in patients. Both findings may influence the risk of treatment failure, resistance development, and toxicity and require further investigation, especially with regard to ongoing high-dose rifampin trials.

Factors Affecting the Pharmacokinetics of Pyrazinamide and Its Metabolites in Patients Coinfected with HIV and Implications for Individualized Dosing.

Pyrazinamide is a first-line drug used in the treatment of tuberculosis. High exposure to pyrazinamide and its metabolites may result in hepatotoxicity, whereas low exposure to pyrazinamide has been correlated with treatment failure of first-line antitubercular therapy. The aim of this study was to describe the pharmacokinetics and metabolism of pyrazinamide in patients coinfected with tuberculosis and HIV. We further aimed to identify demographic and clinical factors which affect the pharmacokinetics of pyrazinamide and its metabolites in order to suggest individualized dosing regimens. Plasma concentrations of pyrazinamide, pyrazinoic acid, and 5-hydroxypyrazinamide from 63 Rwandan patients coinfected with tuberculosis and HIV were determined by liquid chromatography-tandem mass spectrometry followed by nonlinear mixed-effects modeling. Females had a close to 50% higher relative pyrazinamide bioavailability compared to males. The distribution volumes of pyrazinamide and both metabolites were lower in patients on concomitant efavirenz-based HIV therapy. Furthermore, there was a linear relationship between serum creatinine and oral clearance of pyrazinoic acid. Simulations indicated that increasing doses from 25 mg/kg of body weight to 35 mg/kg and 50 mg/kg in females and males, respectively, would result in adequate exposure with regard to suggested thresholds and increase probability of target attainment to >0.9 for a MIC of 25 mg/liter. Further, lowering the dose by 40% in patients with high serum creatinine would prevent accumulation of toxic metabolites. Individualized dosing is proposed to decrease variability in exposure to pyrazinamide and its metabolites. Reducing the variability in exposure may lower the risk of treatment failure and resistance development.

Effect of efavirenz-based ART on the pharmacokinetics of rifampicin and its primary metabolite in patients coinfected with TB and HIV.

OBJECTIVES: To evaluate the effects of concomitant efavirenz-based ART and genetic polymorphism on the variability in rifampicin and 25-desacetylrifampicin pharmacokinetics. PATIENTS AND METHODS: Plasma concentrations of rifampicin and 25-desacetylrifampicin from 63 patients coinfected with TB and HIV were analysed by LC-MS/MS followed by non-linear mixed-effects modelling. Patients were genotyped for SLCO1B1 (463 C>A, 388 A>G, 11187 G>A, rs4149015, 521 T>C and 1436 G>C) and SLCO1B3 (334 T>G). RESULTS: One-compartment disposition models described the observations adequately. The oral clearances of rifampicin and 25-desacetylrifampicin were 140% and 110% higher, respectively, in patients on concomitant efavirenz-based ART. Rifampicin bioavailability was also lower in patients on concomitant ART. Further, although not included in the final model, a lower relative bioavailability in carriers of WT SLCO1B3 334 T>G compared with carriers of mutations in the genotype was estimated. CONCLUSIONS: The results presented indicate both pre-systemic and systemic induction by efavirenz-based ART affecting rifampicin pharmacokinetics. The described drug-drug interaction has a clinical impact on rifampicin exposure prior to steady state and may impact the early bactericidal activity in patients on efavirenz-based ART.

On the relations between HEXACO agreeableness (versus anger) and honesty-humility.

The HEXACO personality factors of Agreeableness-versus-Anger (A) and Honesty-Humility (H) are interpreted as two complementary aspects of reciprocal altruistic tendency. Here we consider several ways of representing the positive associations between the defining traits of A and of H, through common factor analysis of self-report HEXACO Personality Inventory-Revised (HEXACO-PI-R) facet scale scores (N ≈ 111,000). We describe orthogonal solutions that differ in the extent to which H facets show secondary loadings on A (and vice versa), as well as an oblique solution compatible with a higher-order "cooperativeness" factor. We discuss the psychological plausibility of these solutions, and we review research showing differential associations of several phenomena or outcomes with A and H. We conclude that the optimal representation of A/H trait associations is not yet known but that the value of separate A and H factor scales is well established.

Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV.

This study aimed to characterize the population pharmacokinetics and pharmacogenetics of ethambutol in tuberculosis-HIV-coinfected adult patients. Ethambutol plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, in 63 patients receiving ethambutol as part of rifampin-based fixed-dose combination therapy for tuberculosis were analyzed using nonlinear mixed-effects modeling. A one-compartment disposition model with first-order elimination and four transit compartments prior to first-order absorption was found to adequately describe the concentration-time profiles of ethambutol in plasma. Body weight was implemented as an allometric function on the clearance and volume parameters. Estimates of oral clearance and volume of distribution were 77.4 liters/h and 76.2 liters, respectively. A G/A mutation with regard to CYP1A2 2159 G>A was associated with a 50% reduction in relative bioavailability. Simulations revealed that doses of 30 mg/kg of body weight and 50 mg/kg for G/G and G/A carriers, respectively, would result in clinically adequate exposure. The results presented here suggest that CYP1A2 polymorphism affects ethambutol exposure in this population and that current treatment guidelines may result in underexposure in patients coinfected with tuberculosis and HIV. Based on simulations, a dose increase from15 to 20 mg/kg to 30 mg/kg is suggested. However, the 50-mg/kg dose required to reach therapeutic exposure in G/A carriers may be inappropriate due to the dose-dependent toxicity of ethambutol. Additional studies are required to further investigate CYP450 polymorphism effects on ethambutol pharmacokinetics.

Ab initio Description of Bond Breaking in Large Electric Fields.

Strong (10^{10} V/m) electric fields capable of inducing atomic bond breaking represent a powerful tool for surface chemistry. However, their exact effects are difficult to predict due to a lack of suitable tools to probe their associated atomic-scale mechanisms. Here we introduce a generalized dipole correction for charged repeated-slab models that controls the electric field on both sides of the slab, thereby enabling direct theoretical treatment of field-induced bond-breaking events. As a prototype application, we consider field evaporation from a kinked W surface. We reveal two qualitatively different desorption mechanisms that can be selected by the magnitude of the applied field.

Sex differences in HEXACO personality characteristics across countries and ethnicities.

OBJECTIVE: We examined sex differences in the HEXACO Personality Inventory-Revised (HEXACO-PI-R) factor- and facet-level scales and the associations of national sex differences in those scales with national characteristics such as wealth and gender equality. METHOD: HEXACO-PI-R self-reports were collected online from persons in 48 countries (N = 347,192). RESULTS: (1) Women averaged substantially higher than men in Emotionality and in Honesty-Humility, with (sample-unweighted) mean differences across countries of d = 0.84 and d = 0.37, respectively; (2) the HEXACO-PI-R factor scales showed a rather large multivariate sex difference (D > 1 in most countries), about 19% larger than found in similar samples with the Big Five personality factors, (3) some facet scales belonging to the same factor showed widely varying sex differences, (4) national-level sex differences in Emotionality were larger in wealthy and gender-egalitarian countries, replicating previous counterintuitive findings, but such a tendency was not clearly observed for Honesty-Humility, and (5) within several English-speaking countries, sex differences in Emotionality showed comparatively little ethnic variation, suggesting that societal characteristics may influence the size of sex differences in Emotionality. CONCLUSION: The HEXACO model of personality structure provides some new insights in understanding sex differences in personality at the individual and national levels.

The HEXACO-100 Across 16 Languages: A Large-Scale Test of Measurement Invariance.

The HEXACO Personality Inventory-Revised (HEXACO-PI-R) has become one of the most heavily applied measurement tools for the assessment of basic personality traits. Correspondingly, the inventory has been translated to many languages for use in cross-cultural research. However, formal tests examining whether the different language versions of the HEXACO-PI-R provide equivalent measures of the 6 personality dimensions are missing. We provide a large-scale test of measurement invariance of the 100-item version of the HEXACO-PI-R across 16 languages spoken in European and Asian countries (N = 30,484). Multigroup exploratory structural equation modeling and confirmatory factor analyses revealed consistent support for configural and metric invariance, thus implying that the factor structure of the HEXACO dimensions as well as the meaning of the latent HEXACO factors is comparable across languages. However, analyses did not show overall support for scalar invariance; that is, equivalence of facet intercepts. A complementary alignment analysis supported this pattern, but also revealed substantial heterogeneity in the level of (non)invariance across facets and factors. Overall, results imply that the HEXACO-PI-R provides largely comparable measurement of the HEXACO dimensions, although the lack of scalar invariance highlights the necessity for future research clarifying the interpretation of mean-level trait differences across countries.

Religiousness and the HEXACO personality factors and facets in a large online sample.

OBJECTIVE: To examine the associations of religiousness with personality characteristics. METHOD: We obtained self-ratings of religiousness along with self-reports on the HEXACO Personality Inventory-Revised in a sample of nearly 200,000 online respondents. Respondents also indicated their religious affiliation, religiousness of upbringing, and political orientation; a subset of the respondents also indicated attitudes about immigration and foreign aid. RESULTS: Religiousness showed weak associations (|r|s < 0.15) with several HEXACO factors but somewhat stronger associations with the Fairness and Altruism facets (both rs > 0.20). On those facets, participants with the highest religiousness self-rating (7 on a 1-to-7 scale) averaged about 1 SD higher than did participants with the lowest religiousness self-rating. In addition, religiousness was negatively related to the Unconventionality facet among persons whose upbringing was very religious, but not among persons whose upbringing was very nonreligious. Religiousness/personality associations were generally quite similar within different religious affiliations (Hinduism, Islam, Judaism, Buddhism, and several branches of Christianity) but were stronger within relatively religious countries than within nonreligious countries. Despite the positive association of religiousness with the Altruism facet, religiousness was uncorrelated with pro-out-group attitudes (i.e., favoring multicultural immigration and foreign aid). CONCLUSION: The findings advance our understanding of religiousness/personality associations.

How Well Do Big Five Measures Capture HEXACO Scale Variance?

We examined the ability of several Big Five measures to account for variance in HEXACO Personality Inventory-Revised (HEXACO-PI-R) scales and vice versa. Some Big Five measures accounted for more variance in HEXACO Honesty-Humility than did others, but these differences were largely offset by opposing differences in accounting for variance in HEXACO Agreeableness and Emotionality. As a consequence, the various Big Five measures showed similarly large overall deficiencies in accounting for HEXACO scale variance, relative to variance accounted for in Big Five scales by HEXACO-PI-R scales. The results imply that the use of Big Five instead of HEXACO scales entails a large loss of information, about equal to the amount that would be lost by discarding one of the Big Five scales.

Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis.

BACKGROUND: The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. METHODS AND FINDINGS: A search in PubMed, Embase, ClinicalTrials.gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing <15 kg and 15-25 kg, respectively, and 20.2% lower in pregnant women compared with non-pregnant adults. Lumefantrine exposure decreased with increasing pre-treatment parasitaemia, and the dose limitation on absorption of lumefantrine was substantial. Simulations using the lumefantrine pharmacokinetic model suggest that, in young children and pregnant women beyond the first trimester, lengthening the dose regimen (twice daily for 5 days) and, to a lesser extent, intensifying the frequency of dosing (3 times daily for 3 days) would be more efficacious than using higher individual doses in the current standard treatment regimen (twice daily for 3 days). The model was developed using venous plasma data from patients receiving intact tablets with fat, and evaluations of alternative dosing regimens were consequently only representative for venous plasma after administration of intact tablets with fat. The absence of artemether-dihydroartemisinin data limited the prediction of parasite killing rates and recrudescent infections. Thus, the suggested optimised dosing schedule was based on the pharmacokinetic endpoint of lumefantrine plasma exposure at day 7. CONCLUSIONS: Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment.

Two-Dimensional Intrinsic Half-Metals With Large Spin Gaps.

Through a systematic search of all layered bulk compounds combined with density functional calculations employing hybrid exchange-correlation functionals, we predict a family of three magnetic two-dimensional (2D) materials with half-metallic band structures. The 2D materials, FeCl2, FeBr2, and FeI2, are all sufficiently stable to be exfoliated from bulk layered compounds. The Fe2+ ions in these materials are in a high-spin octahedral d6 configuration leading to a large magnetic moment of 4 µB. Calculations of the magnetic anisotropy show an easy-plane for the magnetic moment. A classical XY model with nearest neighbor coupling estimates critical temperatures, Tc, for the Berezinskii-Kosterlitz-Thouless transition ranging from 122 K for FeI2 to 210 K for FeBr2. The quantum confinement of these 2D materials results in unusually large spin gaps, ranging from 4.0 eV for FeI2 to 6.4 eV for FeCl2, which should defend against spin current leakage even at small device length scales. Their purely spin-polarized currents and dispersive interlayer interactions should make these materials useful for 2D spin valves and other spintronic applications.

Topology-Scaling Identification of Layered Solids and Stable Exfoliated 2D Materials.

The Materials Project crystal structure database has been searched for materials possessing layered motifs in their crystal structures using a topology-scaling algorithm. The algorithm identifies and measures the sizes of bonded atomic clusters in a structure's unit cell, and determines their scaling with cell size. The search yielded 826 stable layered materials that are considered as candidates for the formation of two-dimensional monolayers via exfoliation. Density-functional theory was used to calculate the exfoliation energy of each material and 680 monolayers emerge with exfoliation energies below those of already-existent two-dimensional materials. The crystal structures of these two-dimensional materials provide templates for future theoretical searches of stable two-dimensional materials. The optimized structures and other calculated data for all 826 monolayers are provided at our database (https://materialsweb.org).

Trait Variance and Response Style Variance in the Scales of the Personality Inventory for DSM-5 (PID-5).

Using self- and observer reports on the Personality Inventory for DSM-5 (PID-5) and the HEXACO Personality Inventory-Revised (HEXACO-PI-R), we identified for each inventory several trait dimensions (each defined by both self- and observer reports on the facet-level scales belonging to the same domain) and 2 source dimensions (each defined by self-reports or by observer reports, respectively, on all facet-level scales). Results (N = 217) showed that the source dimensions of the PID-5 were very large (much larger than those of the HEXACO-PI-R), and suggest that self-report (or observer report) response styles substantially inflate the intercorrelations and the alpha reliabilities of the PID-5 scales. We discuss the meaning and the implications of the large PID-5 source components, and we suggest some methods of controlling their influence.

Population pharmacokinetic properties of artemisinin in healthy male Vietnamese volunteers.

BACKGROUND: Artemisinin-based combination therapy is recommended as first-line anti-malarial treatment worldwide. A combination of artemisinin with the long acting drug piperaquine has shown high efficacy and tolerability in patients with uncomplicated Plasmodium falciparum infections. The aim of this study was to characterize the population pharmacokinetic properties of artemisinin in healthy male Vietnamese volunteers after two different dose sizes, formulations and in a combination with piperaquine. A secondary aim was to compare two different methods for the evaluation of bioequivalence of the formulations. METHODS: Fifteen subjects received four different dose regimens of a single dose of artemisinin as a conventional formulation (160 and 500 mg) and as a micronized test formulation (160 mg alone and in combination with piperaquine phosphate, 360 mg) with a washout period of 3 weeks between each period (i.e. four-way cross-over). Venous plasma samples were collected frequently up to 12 h after dose in each period. Artemisinin was quantified in plasma using liquid chromatography coupled with tandem mass spectrometry. A nonlinear mixed-effects modelling approach was utilized to evaluate the population pharmacokinetic properties of the drug and to investigate the clinical impact of different formulations. RESULTS: The plasma concentration-time profiles for artemisinin were adequately described by a transit-absorption model with a one-compartment disposition, in all four sequences simultaneously. The mean oral clearance, volume of distribution and terminal elimination half-life was 417 L/h, 1210 L and 1.93 h, respectively. Influence of formulation, dose and possible interaction of piperaquine was evaluated as categorical covariates in full covariate approaches. No clinically significant differences between formulations were shown which was in accordance with the previous results using a non-compartmental bioequivalence approach. CONCLUSIONS: This is the first population pharmacokinetic characterization of artemisinin in healthy volunteers. Increasing the dose resulted in a significant increase in the mean transit-time but the micronized formulation or concomitant piperaquine administration did not affect the pharmacokinetic properties of artemisinin. The results from the traditional bioequivalence evaluation were comparable with results obtained from mixed-effects modelling.

Artemether-lumefantrine co-administration with antiretrovirals: population pharmacokinetics and dosing implications.

AIM: Drug-drug interactions between antimalarial and antiretroviral drugs may influence antimalarial treatment outcomes. The aim of this study was to investigate the potential drug-drug interactions between the antimalarial drugs, lumefantrine, artemether and their respective metabolites desbutyl-lumefantrine and dihydroartemisinin, and the HIV drugs efavirenz, nevirapine and lopinavir/ritonavir. METHOD: Data from two clinical studies, investigating the influence of the HIV drugs efavirenz, nevirapine and lopinavir/ritonavir on the pharmacokinetics of the antimalarial drugs lumefantrine, artemether and their respective metabolites, in HIV infected patients were pooled and analyzed using a non-linear mixed effects modelling approach. RESULTS: Efavirenz and nevirapine significantly decreased the terminal exposure to lumefantrine (decrease of 69.9% and 25.2%, respectively) while lopinavir/ritonavir substantially increased the exposure (increase of 439%). All antiretroviral drugs decreased the total exposure to dihydroartemisinin (decrease of 71.7%, 41.3% and 59.7% for efavirenz, nevirapine and ritonavir/lopinavir, respectively). Simulations suggest that a substantially increased artemether-lumefantrine dose is required to achieve equivalent exposures when co-administered with efavirenz (250% increase) and nevirapine (75% increase). When co-administered with lopinavir/ritonavir it is unclear if the increased lumefantrine exposure compensates adequately for the reduced dihydroartemisinin exposure and thus whether dose adjustment is required. CONCLUSION: There are substantial drug interactions between artemether-lumefantrine and efavirenz, nevirapine and ritonavir/lopinavir. Given the readily saturable absorption of lumefantrine, the dose adjustments predicted to be necessary will need to be evaluated prospectively in malaria-HIV co-infected patients.

Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer.

PURPOSE: The purpose of this study were firstly to characterize the population pharmacokinetics of artesunate (ARS) and its active metabolite dihydroartemisinin (DHA) in patients with metastatic breast cancer during long-term (>3 weeks) daily oral ARS administration and secondly to study the relationship between salivary and plasma concentrations of DHA. METHODS: Drug concentration-time data from 23 patients, receiving oral ARS (100, 150, or 200 mg OD), was analyzed using nonlinear mixed effects modeling. A combined drug-metabolite population pharmacokinetic model was developed to describe the plasma pharmacokinetics of ARS and DHA in plasma. Saliva drug concentrations were incorporated as being directly proportional to plasma concentrations. RESULTS: A first-order absorption model for ARS linked to a combined two-compartment disposition model for ARS and one-compartment disposition model for DHA provided the best fit to the data. No covariates were identified that could explain between-subject variability. A time-dependent increase in apparent elimination clearance of DHA was observed. Salivary DHA concentrations were proportionally correlated with total DHA plasma concentrations, with an estimated slope factor of 0.116. CONCLUSIONS: Population pharmacokinetics of ARS and DHA in patients with breast cancer was well described by a combined drug-metabolite model without any covariates and with an increase in apparent elimination clearance of DHA over time. The estimated DHA saliva/plasma ratio was in good agreement with the reported DHA unbound fraction in human plasma. Saliva ARS concentrations correlated poorly with plasma concentrations. This suggests the use of saliva sampling for therapeutic drug monitoring of DHA. However, further studies are warranted to investigate the robustness of this approach.

The HEXACO Honesty-Humility, Agreeableness, and Emotionality factors: a review of research and theory.

We review research and theory on the HEXACO personality dimensions of Honesty-Humility (H), Agreeableness (A), and Emotionality (E), with particular attention to the following topics: (1) the origins of the HEXACO model in lexical studies of personality structure, and the content of the H, A, and E factors in those studies; (2) the operationalization of the H, A, and E factors in the HEXACO Personality Inventory-Revised; (3) the construct validity of self-reports on scales measuring the H factor; (4) the theoretical distinction between H and A; (5) similarity and assumed similarity between social partners in personality, with a focus on H and A; (6) the extent to which H (and A and E) variance is represented in instruments assessing the "Five-Factor Model" of personality; and (7) the relative validity of scales assessing the HEXACO and Five-Factor Model dimensions in predicting criteria conceptually relevant to H, A, and E.