Evaluating the QileX-RhE skin corrosion test for chemical subcategorization in accordance with OECD TG 431.

Skin corrosion testing is integral to evaluating the potential harm posed by chemicals, impacting regulatory decisions on safety, transportation, and labeling. Traditional animal testing methods are giving way to in vitro alternatives, such as reconstructed human epidermis (RhE) models, aligning with evolving ethical standards. This study evaluates the QileX-RhE test system's performance for chemical subcategorization within the OECD TG 431 framework. Results demonstrate its ability to differentiate subcategories, accurately predicting 83% of UN GHS Category 1A and 73% of UN GHS Category 1B/1C chemicals with 100% sensitivity in corrosive prediction. Additionally, this study provides a comprehensive assessment of the test method's performance by employing nuanced parameters such as positive predictive value (PPV), negative predictive value (NPV), post-test odds and likelihood rations, offering valuable insights into the applicability and effectiveness of the QileX-RhE test method.

Rigidez carotídea y riesgo de eventos vasculares y mortalidad: el estudio REGICOR / Carotid artery stiffness and risk of vascular events and mortality: the REGICOR study

Introducción y objetivos: Los objetivos son analizar la relación dosis-respuesta de la rigidez de la arteria carótida y la mortalidad y evaluar su capacidad predictiva. Métodos: Estudio de cohorte poblacional que incluyó a 6.468 participantes, con una mediana de seguimiento de 6,5 años. Se evaluaron 6 índices de rigidez. Se identificaron los eventos coronarios y cerebrovasculares y la mortalidad. Resultados: La rigidez carotídea, el coeficiente de Peterson y la velocidad de la onda de pulso (VOP) se asociaron de manera lineal y directa con los eventos cerebrovasculares: aumento del 8% (IC95%, 1-16%) por unidad de rigidez, del 7% (IC95%, 2-13%) cada 10 unidades del coeficiente de Peterson y del 26% (IC95%, 8-48%) por unidad de la VOP. La tensión carotídea se asoció de modo no lineal con el riesgo de enfermedad coronaria: en valores <0,09 unidades, cada aumento de 0,01 unidades se asoció con una disminución de un 16% del riesgo (IC95%, –33 a +6%); por encima de 0,09 unidades, cada incremento de 0,01 unidades se asoció con un aumento de un 16% del riesgo (IC95%, 6-27%). La inclusión de estos índices no mejoró la capacidad predictiva de las funciones de riesgo. Conclusiones: La rigidez carotídea, el coeficiente de elasticidad de Peterson y la VOP tienen una relación lineal y directa con el riesgo de enfermedad cerebrovascular. La tensión (strain) carotídea tiene una relación en U con el riesgo de enfermedad coronaria. Estos índices no contribuyen a mejorar la capacidad predictiva de las funciones de riesgo. (AU)

Introduction and objectives: The aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. Methods: Population-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. Results: Carotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,−33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. Conclusions: Carotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions. (AU)

Carotid artery stiffness and risk of vascular events and mortality: the REGICOR study.

INTRODUCTION AND OBJECTIVES: The aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. METHODS: Population-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. RESULTS: Carotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,-33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. CONCLUSIONS: Carotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions.

Optimal objective measurement of physical function and its predictive capacity for mortality among community-dwelling older women.

AIM: Objective measurements of physcial function, including gait speed, handgrip strength, and the chair stand test, have been shown to have predictive capacity for negative health-related outcomes. The aim of this study was to examine campariatively which of these common assessments may be optimal in terms of their predictive capacity for mortality. METHODS: A total of 9834 community-dwelling older women aged 65-89 years from the Study of Osteoporotic Fractures (SOF) were followed for 20 years. Gait speed, handgrip strength, and the chair stand test were measured every 2-4 years on up to 9 visits. All deaths were adjudicated. RESULTS: All three measurements of physical function were significantly associated with overall, cardiovascular disease and other mortality. Gait speed had the greatest magnitude of hazard ratios (HRs) for all outcomes of interest. A one-unit standard deviation increase in gait speed was associated with a 33% (HR = 0.67, 95% confidence interval [95% CI]: 0.64-0.70) lower risk for overall mortality, a 31% (HR = 0.69, 95% CI: 0.64-0.73) lower risk for cardiovascular disease mortality, a 15% (HR = 0.85, 95% CI: 0.78-0.92) lower risk for cancer mortality and a 42% (HR = 0.58, 95% CI: 0.55-0.62) lower risk for other mortality. Further examination of gait speed identified two cut-points (0.9 and 0.7 m/s) that were strongly indicative of increased mortality risk. CONCLUSION: Our large prospective study indicates that gait speed possesses a better prediction of mortality among older women compared with handgrip strength or the chair stand test. Using cut-points of 0.9 and 0.7 m/s can help identify older women at higher mortality risk, who may benefit from physical function improvement interventions. Geriatr Gerontol Int 2023; 23: 715-721.

Preliminary Study on an Alternative Test Method with MCTT HCETM for Ocular Irritation Test of Ophthalmic Medical Devices.

The sustained growth of the market for ophthalmic medical devices has increased the demand for alternatives to animal testing for the evaluation of eye irritation. The International Organization for Standardization has acknowledged the need to develop novel in vitro tests to replace animal testing. Here, we evaluated the applicability of an alternative method based on a human corneal model to test the safety of ophthalmic medical devices. 2-Hydroxyethyl methacrylate (HEMA) and Polymethyl methacrylate (PMMA), which are used to fabricate contact lenses, were used as base materials. These materials were blended with eye irritant and non-irritant chemicals specified in the OECD Test Guideline (TG) 492 and Globally Harmonized System (GHS) classification. Then, three GLP-certified laboratories performed three replicates using the developed method using 3D reconstructed human cornea epithelium, MCTT HCETM. OECD TG 492 describes the procedure used to evaluate the eye hazard potential of the test chemical based on its ability to induce cytotoxicity in a reconstructed human cornea-like epithelium (RhCE) tissue. Results: The within-laboratory reproducibility (WLR) and between-laboratory reproducibility (BLR) were both 100%. When a polar extraction solvent was used, the sensitivity, specificity, and accuracy were all 100% in each laboratory. When a non-polar extraction solvent was used, the sensitivity was 80%, the specificity was 100%, and the accuracy was 90%. The proposed method exhibited excellent reproducibility and predictive capacity within and between laboratories. Therefore, the proposed method using the MCTT HCETM model could be used to evaluate eye irritation caused by ophthalmic medical devices.

Early Efficacy of Antipsychotic Medications at Week 2 Predicts Subsequent Responses at Week 6 in a Large-scale Randomized Controlled Trial.

BACKGROUND: Since the early clinical efficacy of antipsychotics has not yet been well perceived, this study sought to decide whether the efficacy of antipsychotics at week 2 can predict subsequent responses at week 6 and identify how such predictive capacities vary among different antipsychotics and psychotic symptoms. METHODS: A total of 3010 patients with schizophrenia enrolled in a randomized controlled trial (RCT) and received a 6-week treatment with one antipsychotic drug randomly chosen from five atypical antipsychotics (risperidone 2-6 mg/d, olanzapine 5-20 mg/d, quetiapine 400-750 mg/d, aripiprazole 10-30 mg/d, and ziprasidone 80-160 mg/d) and two typical antipsychotics (perphenazine 20-60 mg/d and haloperidol 6-20 mg/d). Early efficacy was defined as the reduction rate using the Positive and Negative Syndrome Scale (PANSS) total score at week 2. With cut-offs at 50% reduction, logistic regression, receiver operating characteristic (ROC) and random forests were adopted. RESULTS: The reduction rate of PANSS total score and improvement of psychotic symptoms at week 2 enabled subsequent responses to 7 antipsychotics to be predicted, in which improvements in delusions, lack of judgment and insight, unusual thought content, and suspiciousness/ persecution were endowed with the greatest weight. CONCLUSION: It is robust enough to clinically predict treatment responses to antipsychotics at week 6 using the reduction rate of PANSS total score and symptom relief at week 2. Psychiatric clinicians had better determine whether to switch the treatment plan by the first 2 weeks.

Pressure injuries in surgical patients: a comparison of Norton, Braden and Waterlow risk assessment scales.

OBJECTIVE: This study aims to determine the predictive power of the Norton, Braden and Waterlow scales in determining risk of pressure injury (PI) in surgical patients. METHOD: This prospective study was carried out in the surgery clinic of a training and research hospital in Istanbul, Turkey between January and April 2017. The study sample consisted of adult patients aged ≥18 years and who did not have PI on admission to the clinic, had abdominal surgery under general anaesthesia and who stayed in the clinic for at least 48 hours. The data were collected using the Turkish versions of the Norton, Braden and Waterlow risk assessment scales. The predictive validity of PI risk assessment tools was assessed based on their sensitivity, specificity, positive and negative predictive values and the area under the receiver operating characteristic (ROC) curve. Predictive capacity was measured as relative risk (RR) with 95% confidence intervals (CI). RESULTS: The study sample included 250 patients, and the incidence of PI was 12%. The sensitivity, specificity, positive predictive value and negative predictive value were: 83.3%, 45.4%, 17.2% and 95.2%, respectively, for the Norton scale (a cut-off point of 14); 100%, 40.4%, 18.6% and 100%, respectively, for the Braden scale (a cut-off point of 16); and 100%, 48.1%, 20.8% and 100%, respectively, for the Waterlow scale (a cut-off point of 10). The areas under the ROC curve were 0.749 for the Norton, 0.771 for the Braden and 0.971 for the Waterlow scales. This study's findings produced the following predictive capacity indicators: Norton (RR=3.62; 95%CI=1.43-9.14), Braden (RR=33.88; 95%CI=2.09-547.66); and Waterlow (RR=45.01; 95%CI=2.78-727.97). CONCLUSION: In this study, the Waterlow scale demonstrated the best values of predictive validity among the three scales in the assessment of PI risk. However, all three scales had low specificity despite high sensitivity in terms of a good risk prediction. No definitive decision could be reached on the predictive capacities of the scales because of wide CIs.

Within- and between-laboratory reproducibility and predictive capacity of amino acid derivative reactivity assay (ADRA) using a 0.5 mg/mL test chemical solution: Results of the study for reproducibility confirmation implemented in five participating laboratories.

The amino acid derivative reactivity assay (ADRA) is an in chemico alternative assay for skin sensitization listed in OECD test guideline 442C. ADRA evaluates the reactivity of sensitizers to proteins, which is key event 1 in the skin sensitization adverse outcome pathway. Although the current key event 1 evaluation method is a simple assay that evaluates nucleophile and test chemical reactivity, mixtures of unknown molecular weights cannot be evaluated because a constant molar ratio between the nucleophile and test chemical is necessary. In addition, because the nucleophile is quantified by HPLC, the frequency of co-eluting the test chemical and nucleophile increases when measuring multi-component mixtures. To solve these issues, test conditions have been developed using a 0.5 mg/mL test chemical solution and fluorescence-based detection. Since the practicality of these methods has not been substantiated, a validation test to confirm reproducibility was conducted in this study. The 10 proficiency substances listed in the ADRA guidelines were tested three times at five different laboratories. The results of both within- and between-laboratory reproducibility were 100%, and the results of ultraviolet- and fluorescence-based measurements were also consistent. In addition to the proficiency substances, a new positive control, squaric acid diethyl ester, was tested three times at the five laboratories. The results showed high reproducibility with N-(2-(1-naphthyl)acetyl)-l-cysteine depletion of 37%-52% and α-N-(2-(1-naphthyl)acetyl)-l-lysine depletion of 99%-100%. Thus, high reproducibility was confirmed in both evaluations of the 0.5 mg/mL test chemical and the fluorescence-based measurements, validating the practicability of these methods.

The within- and between-laboratories reproducibility and predictive capacity of Amino acid Derivative Reactivity Assay using 4 mM test chemical solution: Results of ring study implemented at five participating laboratories.

Amino acid derivative reactivity assay (ADRA) for skin sensitization was adopted as an alternative method in the 2019 OECD Guideline for the Testing of Chemicals (OECD TG 442C). The molar ratio of the nucleophilic reagent to the test chemicals in the reaction solution was set to 1:50. Imamura et al. reported that changing this molar ratio from 1:50 to 1:200 reduced in false negatives and improved prediction accuracy. Hence, a ring study using ADRA with 4 mM of a test chemical solution (ADRA, 4 mM) was conducted at five different laboratories to verify within- and between-laboratory reproducibilities (WLR and BLR, respectively). In this study, we investigated the WLR and BLR using 14 test chemicals grouped into three classes: (1) eight proficiency substances, (2) four test chemicals that showed false negatives in the ADRA with 1 mM test chemical solution (ADRA, 1 mM), but correctly positive in ADRA (4 mM), and (3) current positive control (phenylacetaldehyde) and a new additional positive control (squaric acid diethyl ester). The results showed 100% reproducibility and 100% accuracy for skin sensitization. Hence, it is clear that the ADRA (4 mM) is an excellent test method in contrast to the currently used ADRA (1 mM). We plan to resubmit the ADRA (4 mM) test method to the OECD Test Guideline Group in the near future so that OECD TG 442C could be revised for the convenience and benefit of many ADRA users.

The External Validity of Sluggish Cognitive Tempo Versus Inattention in Behavioral, Social Interaction, and Academic Performance Measures / La Validez Externa del Tempo Cognitivo Lento Frente a la Inatención en Medidas Comportamentales, de Interacción Social y de Rendimiento Académico

Background: The main objective was to replicate data on the external validity of the Sluggish Cognitive Tempo (SCT) dimension, versus ADHD Inattention (IN), with the Spanish version of the Child and Adolescent Behavior Inventory (CABI) SCT subscale [Cuestionario sobre el Comportamiento de Niños] (Burns et al., 2015). Method: 273 mothers and 255 fathers evaluated their 9 to13 year old children on SCT, IN and other CABI internalizing externalizing, academic impairment and social interaction measures. Results: As hypothesized, the relationship between SCT and externalizing measures, in contrast to IN, was practically nonexistent, whereas both measures were related to internalizing and social interaction measures. Thus, the unique predictive capacity of SCT and IN was significant and similar on internalizing measures, except in the case of shyness, where SCT was better, while IN was better on externalizing measures. Conclusions: The data largely replicated previous results: SCT, despite its relationship with IN, is capable of predicting a significant proportion of anxiety, depression, and excessive shyness problems and, unlike IN, functions as a protective measure for externalizing problems.(AU)

Antecedentes: El objetivo principal del presente trabajo ha sido replicar datos de la validez externa de la dimensión Tempo Cognitivo Lento (TCL), frente a inatención del TDAH (IN), con la versión española de la medida del TCL del Child and Adolescent Behavior Inventory (CABI) [Cuestionario sobre el Comportamiento de Niños] (Burns et al., 2015). Método: 273 madres y 255 padres evaluaron a sus hijos entre 9 y 13 años en TCL, IN y otras medidas internalizadas, externalizadas, de dificultades académicas e interacción social del CABI. Resultados: La relación de TCL con las medidas externalizadas, al contrario de IN, fue prácticamente nula, en cambio ambas medidas se relacionaron con las medidas internalizadas y de interacción social. La capacidad predictiva única de TCL e IN fue significativa y similar sobre las medidas internalizadas, excepto en el caso de timidez, donde TCL fue superior y, en cambio, en las medidas externalizadas fue superior IN. Conclusiones: Los datos replican en gran parte los resultados previos: el TCL, a pesar de su relación con IN, es capaz de predecir una parte significativa de problemas de ansiedad, depresión y timidez excesiva y, en cambio, al contrario de IN, resulta una medida protectora para los problemas externalizados.(AU)

Uric acid: A new marker for metabolic syndrome? Results of a population-based study with adults.

BACKGROUND AND AIMS: Recently, studies have shown a positive association between serum uric acid (UA) and metabolic syndrome (MS). To evaluate the predictive capacity and the association of serum UA with pre-MS and MS, by sex, in adults. METHODS AND RESULTS: Cross-sectional study with 932 adults, of both sexes, from Viçosa, Minas Gerais (MG), Brazil. Sociodemographic and behavioral data were obtained through a questionnaire and anthropometric, clinical, and biochemical evaluation. We used multinomial logistic regression and the area under receiver operating characteristic curve (AUC). The prevalence of pre-MS was 17.8% and of MS was 26.5%. The fitted models showed positive association of serum UA with pre-MS (OR = 1.62, 95% CI = 1.09-2.40) and MS (OR = 2.61, 95% CI = 1.99-3.42) among men. For women, similar results were found for MS (OR = 2.59, 95% CI = 1.81-3.73). The optimal cutoff points obtained by AUC for pre-MS and MS were 4.7 and 4.9 mg/dL among men and 3.1 and 3.4 mg/dL among women, respectively. CONCLUSION: The results point to a positive association of UA with pre-MS and MS, with no significant differences between sexes. Therefore, UA can be used as an additional marker in the screening of these conditions.

Predictive Capacity of COVID-19 Test Positivity Rate.

COVID-19 infections can spread silently, due to the simultaneous presence of significant numbers of both critical and asymptomatic to mild cases. While, for the former reliable data are available (in the form of number of hospitalization and/or beds in intensive care units), this is not the case of the latter. Hence, analytical tools designed to generate reliable forecast and future scenarios, should be implemented to help decision-makers to plan ahead (e.g., medical structures and equipment). Previous work of one of the authors shows that an alternative formulation of the Test Positivity Rate (TPR), i.e., the proportion of the number of persons tested positive in a given day, exhibits a strong correlation with the number of patients admitted in hospitals and intensive care units. In this paper, we investigate the lagged correlation structure between the newly defined TPR and the hospitalized people time series, exploiting a rigorous statistical model, the Seasonal Auto Regressive Moving Average (SARIMA). The rigorous analytical framework chosen, i.e., the stochastic processes theory, allowed for a reliable forecasting about 12 days ahead of those quantities. The proposed approach would also allow decision-makers to forecast the number of beds in hospitals and intensive care units needed 12 days ahead. The obtained results show that a standardized TPR index is a valuable metric to monitor the growth of the COVID-19 epidemic. The index can be computed on daily basis and it is probably one of the best forecasting tools available today for predicting hospital and intensive care units overload, being an optimal compromise between simplicity of calculation and accuracy.

The predictive capacity of AUDIT and AUDIT-C among adolescents in a one-year follow-up study.

AIM: The Alcohol Use Disorders Identification Test (AUDIT) has been validated for use with adolescents to screen their harmful alcohol consumption. How well AUDIT or its derivative consumption version AUDIT-C predicts the development of problematic alcohol use among adolescents remains unknown. The aim of our study was to examine the predictive capacity of AUDIT and AUDIT-C among adolescents in a one-year follow-up. METHODS: Finnish adolescents (N = 337) were examined at baseline with AUDIT and one year later with the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime version (K-SADS-PL) interview to assess alcohol problem use. Test characteristics and regression models were analyzed in predicting alcohol problem use. RESULTS: The sensitivity of AUDIT (cut-off ≥5) was 0.809 and specificity 0.621 in predicting alcohol problem use among adolescents one year later. The positive test posterior probability was 0.51. For those who screened negative at baseline, the positive test posterior probability was 0.13. With AUDIT-C (cut-off ≥3), the posterior probabilities were 0.47 and 0.12, respectively (sensitivity 0.855, specificity 0.529). The odds ratio was 6.95 for those screening positive with AUDIT and 6.59 with AUDIT-C at baseline to have alcohol problem use one year later. CONCLUSIONS: AUDIT has utility in screening youth at risk for developing alcohol problem use. It has significant predictive capacity in detecting risk especially among adolescents with depression.

Me-too validation study for in vitro skin irritation test with a reconstructed human epidermis model, KeraSkin™ for OECD test guideline 439.

We conducted a me-too validation study to confirm the reproducibility, reliability, and predictive capacity of KeraSkin™ skin irritation test (SIT) as a me-too method of OECD TG 439. With 20 reference chemicals, within-laboratory reproducibility (WLR) of KeraSkin™ SIT in the decision of irritant or non-irritant was 100%, 100%, and 95% while between-laboratory reproducibility (BLR) was 100%, which met the criteria of performance standard (PS, WLR≥90%, BLR≥80%). WLR and BLR were further confirmed with intra-class correlation (ICC, coefficients >0.950). WLR and BLR in raw data (viability) were also shown with a scatter plot and Bland-Altman plot. Comparison with existing VRMs with Bland-Altman plot, ICC and kappa statistics confirmed the compatibility of KeraSkin™ SIT with OECD TG 439. The predictive capacity of KeraSkin™ SIT was estimated with 20 reference chemicals (the sensitivity of 98.9%, the specificity of 70%, and the accuracy of 84.4%) and additional 46 chemicals (for 66 chemicals [20 + 46 chemicals, the sensitivity, specificity and accuracy: 95.2%, 82.2% and 86.4%]). The receiver operating characteristic (ROC) analysis suggested a potential improvement of the predictive capacity, especially sensitivity, when changing cut-off (50% → 60-75%). Collectively, the me-too validation study demonstrated that KeraSkin™ SIT can be a new me-too method for OECD TG 439.

Two tiered approaches combining alternative test methods and minimizing the use of reconstructed human cornea-like epithelium tests for the evaluation of eye irritation potency of test chemicals.

In order to overcome the limitations of single in vitro eye irritation tests, Integrated Approaches to Testing Assessment strategies have been suggested for evaluating eye irritation. This study developed two tiered approaches combining alternative test methods. They were designed in consideration of the solubility property of test chemicals and to use the RhCE tests at final steps. The tiered approach A is composed of the STE, BCOP, HET-CAM or RhCE tests, whereas the tiered approach B is designed to perform simultaneously two in vitro test methods at the first stage and the RhCE test at the final stage. The predictive capacity of the two tiered approaches was estimated using 47 chemicals. The accuracy, sensitivity, and specificity value of the tiered approach A were 95.7% (45/47), 100% (34/34), and 84.6% (11/13), respectively, whereas those of the tiered approach B were 95.7% (45/47), 97.1% (33/34), and 92.3% (12/13), respectively. The approach A and B were considered to be available methods for distinguishing test chemicals of Category 1 (all 73.3%) and No Category (84.6% and 92.3%), respectively. Especially, the approach B was considered as an efficient method as the Bottom-Up approach, because it predicted correctly test chemicals classified as No Category.

The within- and between-laboratory reproducibility and predictive capacity of the in chemico amino acid derivative reactivity assay: Results of validation study implemented in four participating laboratories.

The amino acid derivative reactivity assay (ADRA) is an in chemico alternative method that focuses on protein binding as the molecular initiating event for skin sensitization. It is a simple and versatile method that has successfully solved some of the problems of the direct peptide reactivity assay (DPRA). The transferability and within- and between-laboratory reproducibility of ADRA were evaluated and confirmed as part of a validation study conducted at four participating laboratories. The transfer of ADRA technology from the lead laboratory to the four participating laboratories was completed successfully during a two-step training program, after which the skin sensitization potentials of 40 coded chemicals were predicted based on the results of ADRA testing. Within-laboratories reproducibility was 100% (10 of 10), 100% (10 of 10), 100% (7 of 7) and 90% (9 of 10), or an average of 97.3% (36 of 37); between-laboratory reproducibility as calculated on the results of three laboratories at the time was 91.9%. The overall predictive capacity comprised an accuracy of 86.9%, sensitivity of 81.5% and specificity of 98.1%. These results satisfied the targets set by the validation management team for demonstrating transferability, within- and between-laboratory reproducibility, and predictive capacity as well as gave a clear indication that ADRA is easily transferable and sufficiently robust to be used in place of DPRA.

Statistical analysis of the reproducibility and predictive capacity of MCTT HCE™ eye irritation test, a me-too test method for OECD TG 492.

We aimed to conduct additional statistical analysis of the reproducibility and predictive capacity of MCTT HCE™ eye irritation test (EIT), a me-too test method for OECD TG 492 with the data generated during the validation study in which 30 reference chemicals were tested in three repeated runs by three independent laboratories. We evaluated the within-laboratory reproducibility (WLR) and the between-laboratory reproducibility (BLR) through tabulation and graphs and presented the concordance of eye irritancy prediction with 95% Wilson's confidence intervals (CIs). Also, the analyses of the Intra-Class Correlation Coefficient (ICC) and Bland-Altman plot were applied to confirm the reproducibility and the comparability, referring to the validated methods of OECD TG 492. Kappa analysis was also performed to check the degree of agreement of the within- and between-laboratory reproducibility and agreement between MCTT HCE™ EIT and the reference methods. We calculated the predictive capacity via misprediction over total prediction method. The predictive capacity (sensitivity, specificity, and accuracy) was presented with 95% of Wilson's CIs. Also, bootstrap resampling was performed to express the 95% CI by the simple percentile methods for 30 chemicals and 141 reference chemicals additionally tested. Collectively, WLR (92.2%) and BLR (93.3%) met the criteria of the performance standards (WLR ≥ 90% and BLR ≥ 85%), and the results of ICC analysis and the Bland-Altman plot suggested an acceptable WLR and BLR and comparability to other validated methods of OECD TG 492. Also, the predictive capacity results for the 30 reference chemicals confirmed the good performance of the MCTT HCE™ EIT by satisfying the criteria of sensitivity, specificity, and the accuracy stated in the PS. The bootstrap resampling method showed a predictive capacity, sufficiently satisfying the criteria stated in the Performance Standards.

A flexible and robust method for assessing conditional association and conditional concordance.

When analyzing bivariate outcome data, it is often of scientific interest to measure and estimate the association between the bivariate outcomes. In the presence of influential covariates for one or both of the outcomes, conditional association measures can quantify the strength of association without the disturbance of the marginal covariate effects, to provide cleaner and less-confounded insights into the bivariate association. In this work, we propose estimation and inferential procedures for assessing the conditional Kendall's tau coefficient given the covariates, by adopting the quantile regression and quantile copula framework to handle marginal covariate effects. The proposed method can flexibly accommodate right censoring and be readily applied to bivariate survival data. It also facilitates an estimator of the conditional concordance measure, namely, a conditional C index, where the unconditional C index is commonly used to assess the predictive capacity for survival outcomes. The proposed method is flexible and robust and can be easily implemented using standard software. The method performed satisfactorily in extensive simulation studies with and without censoring. Application of our methods to two real-life data examples demonstrates their desirable practical utility.

Visceral adiposity index is a better predictor of unhealthy metabolic phenotype than traditional adiposity measures: results from a population-based study.

OBJECTIVE: The present study aimed to investigate whether the visceral adiposity index (VAI) is an effective predictor to identify unhealthy metabolic phenotype by comparing normal-weight and overweight individuals. DESIGN: A population-based cross-sectional study. Data were collected by interviews, anthropometric evaluation, dietetic, clinical and laboratory tests. The area under the receiver-operating characteristic curve (AUC) and prevalence ratio (PR), obtained from Poisson regression, were used to compare the predictive capacity of the obesity indicators evaluated (VAI, BMI, waist and neck circumference, waist-to-height and waist-to-hip ratios) and their association with the unhealthy metabolic phenotype. All analyses were stratified by sex and by nutritional status. SETTING: Viçosa, Minas Gerais, Brazil.ParticipantsA total of 854 Brazilian adults (20-59 years old) of both sexes. RESULTS: VAI was the best predictor for unhealthy metabolic phenotype among men (AUC = 0·865) and women (AUC = 0·843) at normal weight. VAI also had the best predictive capacity among overweight women (AUC = 0·903). Among overweight men, its accuracy (AUC = 0·830) was higher than that of waist-to-hip ratio. In the adjusted regression models, VAI was the indicator most strongly associated with the unhealthy metabolic phenotype, especially among those with normal weight (PR = 6·74; 95 % CI 3·15, 14·42 for men; PR = 7·14; 95 % CI 3·79, 13·44 for women). CONCLUSIONS: VAI has better predictive capacity in detecting unhealthy metabolic phenotype than conventional anthropometric indicators, regardless of nutritional status and sex.