Probing Latent Interactions Estimated with a Residual Centering Approach

Understanding latent interactions is an important need for the structural equation modeler. Plotting and probing latent interactions, however, has not been well defined. We describe methods for plotting and probing two- and three-way latent interactions fit with a variety of approaches (LMS/QML, residual centering, double mean centering). The methods are demonstrated through a small simulation and examples based on existing data.

A comparison of root canal transportation and centering ability between WaveOne® Gold and Protaper Next® files, using microcomputed tomography

This study compared the transportation and centering ability of ProTaper Next (PTN) and WaveOne Gold (WOG) files in curved permanent teeth using micro-computed tomography (μCT). Twenty-four molar teeth with curved roots were divided randomly into two equal groups. The root canals of one group was prepared using PTN files, and the other using WOG files. Pre-instrumentation and post-instrumentation μCT imaging were taken for all the teeth. The dentine thickness of the pre-and the post-instrumentation cross sections was measured at eight different points at three levels: 3, 5 and 7mm from the apex, by two dentists using image analysis software. The data were analysed using one-way ANOVA, at a 5% significance level. The transportation in both groups was within the range accepted in the literature. The WOG file exhibited significantly less root canal transportation compared with the PTN file (p=0.001). The WOG file showed a significantly (p<0.001) higher mean centering ratio of 0.4286 when compared to that of PTN at 0.2448. Using a novel technique to measure canal transportation, this study found that the WOG and PTN systems were both suitable for preparation of curved molar root canals, but the WOG showed significantly less canal transportation and better centering ability than the PTN system.

Identification and validation of endogenous control miRNAs in plasma samples for normalization of qPCR data for Alzheimer’s disease

Background MicroRNAs (miRNAs) are noncoding RNAs that are highly relevant as disease biomarkers. Several studies that explored the role of miRNAs in Alzheimer’s disease (AD) demonstrated their usefulness in clinical identification. Nevertheless, miRNAs that may act as endogenous controls (ECs) have not yet been established. The identification of ECs would contribute to the standardization of these biomarkers in AD. The objective of the study was to identify miRNAs that can be used as ECs in AD. Methods We evaluated 145 patients divided into two different cohorts. One was a discovery cohort of 19 women diagnosed with mild to moderate AD (Mini-Mental State Examination (MMSE) score ≥ 20) and with confirmed pathologic levels of Aβ42 in CSF. The stability assessment cohort consisted of 126 individuals: 24 subjects without AD or any kind of dementia and negative for all core CSF biomarkers of AD, 25 subjects with MCI and negative for CSF biomarkers (MCI −), 22 subjects with MCI and positive for CSF biomarkers (MCI +), and 55 subjects with AD and positive for CSF biomarkers. In the discovery cohort, a profile of 384 miRNAs was determined in the plasma by TaqMan low-density array. The best EC candidates were identified by mean-centering and concordance correlation restricted normalization methods. The stability of the EC candidates was assessed using the GeNorm, BestKeeper, and NormFinder algorithms. Results Nine miRNAs (hsa-miR-324-5p, hsa-miR-22-5p, hsa-miR-103a-2-5p, hsa-miR-362-5p, hsa-miR-425-3p, hsa-miR-423-5p, hsa-let-7i-3p, hsa-miR-532-5p, and hsa-miR-1301-3p) were identified as EC candidates in the discovery cohort. The validation results indicated that hsa-miR-103a-2-5p was the best EC, followed by hsa-miR-22-5p, hsa-miR-1301-3p, and hsa-miR-425-3p, which had similar stability values in all three algorithms. Conclusions We identified a profile of four miRNAs as potential plasma ECs to be used for normalization of miRNA expression data in studies of subjects with cognitive impairment.

Comparative Study of Different Derivative Spectrophotometric Techniques for the Analysis and Separation of Metformin, Empagliflozin, and Glimepiride

Background: In some cases, lifestyle changes are not enough to keep type 2 diabetes under control, so there are several medications that may help. Metformin can lower your blood sugar levels, Glimepiride makes more insulin, whereas Empagliflozin prevents the kidneys from reabsorbing sugar into the blood and sending it out in the urine. Methods: Mean centering, double divisor, ratio spectra-zero crossing, and successive derivative were applied for the estimation of metformin, empagliflozin, and glimepiride respectively, in their prepared laboratory mixtures and in pharmaceutical tablets, without prior chemical separation. The absorption spectra of the mentioned drugs were recorded in the range of 200-400nm. Results: These methods were linear over concentration ranges of 1.0-10, 2.5-30, and 1.0-10 μgmL-1 of metformin, empagliflozin, and glimepiride respectively. Mean centering for metformin was measured at 234 and 248 nm, while empagliflozin and glimepiride had amplitude values at 276 and 262 nm, respectively. The derivative of double divisor was measured at 234, 278, and 288 nm for metformin, empagliflozin and glimepiride, respectively. The ratio of spectra-zero crossing was quantified at amplitude values of the analytical signal at 234 and 274 nm for metformin and empagliflozin, respectively, whereas glimepiride was determined at 242 and 286 nm. The successive ratio of metformin, empagliflozin, and glimepiride was determined at 284, 242, and 266 nm, respectively. Conclusion: The methods are validated according to the ICH guidelines where accuracy, precision and repeatability are found to be within the acceptable limit. The methods were studied and optimized. Upon validation linearity, precision, accuracy, LOD, LOQ and selectivity were proved to be operative for the analysis of specified drugs in pharmaceutical dosage configuration. Statistical illustration was done between the suggested methods with the reported methods with consideration to accuracy and precision. No significant difference was found by student’s t-test, F-test and one-way ANOVA.

Eco-friendly spectrophotometric methods for assessment of alfuzosin and solifenacin in their new pharmaceutical formulation; Green profile evaluation via eco-scale and GAPI tools

Background: Alfuzosin is recently co-formulated with solifenacin for relieving two coincident urological diseases, namely; benign prostate hyperplasia and overactive bladder Objective: Herein, green, simple and rapid spectrophotometric methods were firstly developed for simultaneous determination of the two cited drugs in their co-formulated pharmaceutical capsule Methods: Alfuzosin, which is the major component in the dosage form, was directly assayed at its extended wavelength at 330.0 nm. The challenging spectrum of the minor component, solifenacin, was resolved by five spectrophotometric methods, namely; dual wavelength (DW) at 210.0 & 230.0 nm, first derivative (1D) at 222.0 nm, ratio difference (RD) at 217.0 - 271.0 nm , derivative ratio (1DD) at 223.0 and mean centering of ratio spectra (MC) at 217.0 nm Results: The Proposed methods were successfully validated as per ICH guidelines. Alfuzosin showed linearity over the range of 4.0 - 70.0 μg/mL, while that of solifenacin were 4.0 - 50.0 μg/mL for DW, 2.0 - 70.0 μg/mL for 1D and RD methods, 1.0 - 70.0 μg/mL for 1DD and 4.0 - 70.0 μg/mL for MC method. Statistical comparison with their official ones showed no noticeable differences. The methods showed good applicability for assaying drugs in their newly combination. Besides eco-scale, the greenness profile of the methods was assessed and compared with the reported spectrophotometric one via the newest metric tool; green analytical procedure index (GAPI). Conclusions: The proposed methods are superior in not only being smart, accurate, selective, robust and time-saving, but also in using distilled water as an eco-friendly and cheap solvent

Disaggregating Between-Person Time Slope Effects from Within-Person Effects

A primary motivation for conducting longitudinal research is to examine variable relationships at both the between-person (BP) and within-person (WP) levels of analysis. In models with time-varying predictors, the problems of conflating WP residual effects with BP intercept effects are relatively well-known, whereas the potential for additional conflation by BP effects of time has received much less attention. The present study used simulation methods to demonstrate the deleterious impact that ignoring BP relations for time slopes across variables can have on the recovery of contemporaneous or lagged WP effects, as well as BP intercept effects, within common longitudinal models (i.e., in mixed-effects models using person-mean-centering, single-level and multilevel structural equation models, and auto-regressive cross-lag panel models). Recommendations are provided for how to use different options for univariate or multivariate longitudinal models to avoid conflating effects across BP and WP levels of analysis in practice.

Three Spectrophotometric Methods for Quantitative Analysis of Duloxetine in Presence of its Toxic Impurity: 1-Naphthol

Background Duloxetine hydrochloride (DUL) is a drug used to treat depression and anxiety. 1-Naphthol is a potential toxic impurity of DUL, as it causes hepatotoxicity in humans, and it is harmful to aquatic life. Objective Three simple, selective, rapid, accurate and precise methods were developed and validated according to International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision and selectivity for analysis of duloxetine hydrochloride (DUL) in the presence of its potential toxic impurity 1-Naphthol in different laboratory-prepared mixtures and pharmaceutical formulations. Methods Method (A) is the first derivative of the ratio spectra spectrophotometric (1DD) method which allows determination of DUL at 251 nm and 1-Naphthol at 305.2 nm without interference from each other. Method B (dual wavelength) means that two different wavelengths were chosen to each drug, where the absorbance difference at these two wavelengths is equal to zero to the second drug. The chosen two wavelengths for DUL were 221.4 nm and 235.6, where the absorbance difference for 1-naphthol at these two wavelengths was equal to zero. While the chosen wavelengths for 1-naphthol were 247.8 nm and 297 nm, where the absorbance difference for DUL at these two wavelengths was equal to zero. Method (C) is the mean centering of ratio spectra spectrophotometric (MCR) method, which depends on measuring the mean centered values of ratio spectra of both DUL and 1-Naphthol at 226 nm. Results These methods were validated and agreed with the requirements of ICH guidelines with respect to linearity, accuracy, precision and selectivity. Conclusions The results indicate the ability of developed methods to be used for routine quality control analysis of DUL in bulk and pharmaceutical formulations in the presence of its potential impurity 1-Naphthol.

Separation-free spectrophotometric platforms for rapid assessment of combined antiplatelet therapy in complex matrices

Aim: To develop simple and rapid UV-spectrophotometric platforms for the simultaneous quantification of a binary mixture containing clopidogrel bisulphate (CPS) and aspirin (ASP) in complex matrices without prior separation. Experimental: Five mathematical models namely ratio-difference method, mean centering of the ratio spectra, dual wavelength, induced dual wavelength and H-Point Standard Addition method, were utilized for resolving spectral overlap by mathematical processing of ratio and zero-order absorption spectra. Analytes were extracted from tested matrices (whole blood, pharmaceutical formulations and dissolution media buffer) and quantified using the proposed methods. The methods were validated according to ICH guidelines. Results: The developed methods demonstrated limits of detection ranging from 0.67 to 1.09 μg/ml-1 for CPS and 0.49 to 0.71 μg.ml-1 for ASP. All proposed methods allowed for reliable determination of CPS and ASP in complex matrices within reported reference ranges, indicating their potential application for therapeutic drug monitoring and quality control testing.

Hyperspectral Imaging to Assess the Presence of Powdery Mildew (Erysiphe necator) in cv. Carignan Noir Grapevine Bunches

Powdery mildew is a worldwide major fungal disease for grapevine, which adversely affects both crop yield and produce quality. Disease identification is based on visible signs of a pathogen once the plant has already been infected; therefore, techniques that allow objective diagnosis of the disease are currently needed. In this study, the potential of hyperspectral imaging (HSI) technology to assess the presence of powdery mildew in grapevine bunches was evaluated. Thirty Carignan Noir grape bunches, 15 healthy and 15 infected, were analyzed using a lab-scale HSI system (900–1700 nm spectral range). Image processing was performed to extract spectral and spatial image features and then, classification models by means of Partial Least Squares Discriminant Analysis (PLS-DA) were carried out for healthy and infected pixels distinction within grape bunches. The best discrimination was achieved for the PLS-DA model with smoothing (SM), Standard Normal Variate (SNV) and mean centering (MC) pre-processing combination, reaching an accuracy of 85.33% in the cross-validation model and a satisfactory classification and spatial location of either healthy or infected pixels in the external validation. The obtained results suggested that HSI technology combined with chemometrics could be used for the detection of powdery mildew in black grapevine bunches.