High-performance and self-powered visible light photodetector using multiple coupled synergetic effects.

In this work, we demonstrate, for the first time, that coupling together the pyroelectric effect, the photovoltaic effect and the plasmonic effect is a novel method to significantly enhance the performance of self-powered photodetectors in the visible region. Photodetectors based on tri-layered heterojunction of n-Si/p-SnO/n-ZnO through the inclusion of silver (Ag) nanoparticles (NPs) at the SnO/ZnO interface were fabricated. The photo-response of the device, with excitation from a chopped 650 nm wavelength laser, was carefully investigated, and it was shown that the photodetector performance is enhanced the most with the inclusion of spheroidal Ag NPs with ∼70 nm diameter. The Al/Si/SnO/Ag NPs/ZnO/ITO device exhibited an optimum responsivity, detectivity and sensitivity of 210.2 mA W-1, 5.47 × 109 Jones and 15.0 × 104, respectively, together with a rise and fall time of 2.3 and 51.3 µs, respectively, at a laser power density of 317 mW cm-2 and at a chopper frequency of 10 Hz. The present photodetectors are more than twice as responsive as the current best-performing ZnO-based pyro-phototronic photodetectors and they also exhibit other competitive features, such as detectivity, and fall and rise times. Therefore, by exploiting the plasmonic effect of the Ag NPs together with the pyroelectric effect in a ZnO film, and the photovoltaic effect at a Si/SnO junction, all in a single device, photodetectors were developed with state-of-the-art performance for the visible region.

Artificial neural networks applied to quality-by-design: From formulation development to clinical outcome.

Quality-by-Design (QbD) is a methodology used to build quality into products and is characterized by a well-defined roadmap. In this study, the application of Artificial Neural Networks (ANNs) in the QbD-based development of a test drug product is presented, where material specifications are defined and correlated with its performance in vivo. Along with other process parameters, drug particle size distribution (PSD) was identified as a critical material attribute and a three-tier specification was needed. An ANN was built with only five hidden nodes in one hidden layer, using hyperbolic tangent functions, and was validated using a random holdback of 33% of the dataset. The model led to significant and valid prediction formulas for the three responses, with R2 values higher than 0.94 for all responses, both for the training and the validation datasets. The prediction formulas were applied to contour plots and tight limits were set based on the design space and feasible working area for the drug PSD, as well as for process parameters. The manufacturing process was validated through the production of three exhibit batches of 180,000 tablets in the industrial GMP facility, and the ANN model was applied to successfully predict the in vitro dissolution, with a bias of approximately 5%. The product was then tested on two clinical studies (under fasting and fed conditions) and the criteria to demonstrate bioequivalence to the Reference Listed Drug were met. In this study, ANNs were successfully applied to support the establishment of drug specifications and limits for process parameters, bridging the formulation development with in vitro performance and the positive clinical results obtained in the bioequivalence studies.

Effect of acupuncture on pain and quality of life in canine neurological and musculoskeletal diseases.

This prospective study investigated the effects of acupuncture alone or combined with analgesics in chronic pain and quality of life assessed by owners for up to 24 weeks in 181 dogs with neurological and musculoskeletal diseases. The scores before and after the onset of treatment were evaluated using the Wilcoxon test and the evolution of success was evaluated by Kaplan-Meier curves. Differences were considered significant at P < 0.05. The success rates for Helsinki chronic pain index (HCPI), quality of life assessment, and visual analog scales (VAS) for pain and locomotion were 79%, 84%, 78%, and 78% of the animals, respectively, when both diseases and groups of treatment were combined. Dogs with musculoskeletal disorders had greater improvement in HCPI (P = 0.003) and VAS locomotion (P = 0.045) than those with neurological disorders. Use of acupuncture alone or in combination with analgesics reduced pain and improved quality of life in dogs with neurological and musculoskeletal diseases.

Effet de l'acupuncture dans la douleur et la qualité de vie dans les maladies neurologiques et musculo-squelettiques chez le chiens. Cette étude prospective a étudié les effets de l'acupuncture (AP) seul ou combinée avec des analgésiques pour traiter la douleur chronique et de la qualité de vie évaluée par les propriétaires pendant 24 semaines à 181 chiens atteints de maladies neurologiques et musculo-squelettiques. Les scores des animaux ont été évalués avant et après le début du traitement au moyen du test de Wilcoxon et l'évolution du succès par des courbes de Kaplan-Meier. Les différences ont été considérées comme significatives lorsque P < 0,05. Le taux de réussite pour l'indice de la douleur chronique de Helsinki (IDCH), évaluation de la qualité de vie et des échelles visuelles analogiques (EVA) pour la douleur et la locomotion étaient respectivement de 79 %, 84 %, 78 %, et 78 %. des animaux, respectivement, lorsque les deux types de maladies, et les deux groupes de traitement ont été combinés. Les chiens souffrant de maladies musculo-squelettiques ont une plus grande amélioration de IDCH (P = 0,003) et EVA locomotion (P = 0,045) scores que ceux souffrant de maladies neurologiques. Utilisation d'AP seul ou associé à traitements analgésiques réduite la douleur et meilleure qualité de vie chez les chiens atteints de maladies neurologiques et musculo-squelettiques.(Traduit par les auteurs).

Bioequivalence evaluation of three different oral formulations of ciprofloxacin in healthy volunteers.

Two bioequivalence studies were performed in twenty four healthy male volunteers with the objective of comparing the bioavailability of three different oral formulations of ciprofloxacin as immediate release tablets 250, 500 and 750 mg (test formulations) with a reference formulation at 500 and 750 mg strengths forms. In study 1, the subjects were enrolled in a single-dose, open-label, 3-period, crossover randomised study, designed to compare the bioavailability of two test formulations of ciprofloxacin (A and B) as 250 and 500 mg tablets, compared to the reference formulation (C), as 500 mg tablets. In study 2, the same 24-subjects were included in a single-dose, open-label, 2-period, crossover randomised study, designed to compare the bioavailability of one test formulation of ciprofloxacin (A) as compared to the reference formulation (B), both products as 750 mg tablets. In both studies multiple blood samples were collected over 24 hours post-dosing. One washout period of six days was observed between the periods. Plasma was harvested and assayed for ciprofloxacin using a selective and sensitive high-performance liquid chromatography (HPLC) method with UV detection. The pharmacokinetic parameter values of Cmax and tmax were obtained directly from plasma data, ke was estimated by log-linear regression, and AUC was calculated by trapezoidal rule. Different statistical tests were performed on the basis of untransformed and log-transformed data and the overall residual variance from ANOVA. Assuming the accepted tolerance intervals, a beta-error of 20% and 90% confidence intervals (alpha = 0.10) of all the generally accepted tests (Westlake, Schuirmann test and Wilcoxon-Tukey nonparametric tests) showed that the formulations can be considered as bioequivalent with respect to the extent of absorption, given by the AUC0-infinity and with respect to rate of absorption as assessed by Cmax and tmax.

Comparative bioavailability of two immediate release tablets of enalapril/hydrochlorothiazide in healthy volunteers.

A bioequivalence study of two oral formulations of 20/12.5 mg tablets of enalapril/hydrochlorothiazide was carried out in 20 healthy male volunteers according to a single dose, two-sequence, crossover randomized design. One washout period of nine days was observed between the two periods. Multiple samples were collected over 96 hours post-dosing. Bioavailability was evaluated on the basis of plasma concentrations of enalapril and its main active metabolite, enalaprilat and hydrochlorothiazide. Plasma samples were assayed for enalapril, enalaprilat and hydrochlorothiazide using a selective and sensitive high-performance liquid chromatography method with mass spectrometry detection (LC-MS). The pharmacokinetic parameter values of Cmax and tmax were obtained directly from plasma data, k(e) was estimated by log-linear regression, and AUC was calculated by trapezoidal rule. Different statistical tests were performed on the basis of untransformed and log-transformed data and the overall residual variance from ANOVA. Assuming the accepted tolerance intervals, a beta-error of 20% and 90% confidence intervals (alpha = 0.10), all the generally accepted tests (Schuirmann test and Wilcoxon-Tukey and Hauschke nonparametric tests) showed that the formulations can be considered as bioequivalent with respect to the extent of absorption, given by the AUC(0-infinity) and with respect to rate of absorption as assessed by Cmax and tmax.