Linear combination methods for prediction of drug skin permeation

YesMany in-vitro methods for prediction of skin permeability have been reported in literature. Cerasome electrokinetic chromatography is one of the most sophisticated approaches representing a maximum level of similarity to the lipid phase of the stratum corneum. One goal of this study was to investigate the affinity pattern of Cerasome and to compare it with the permeability profile of human skin. Another purpose was to study the applicability of Hansen solubility parameters for modelling skin permeation and to investigate the predictive and explanatory potential of this method. Visualisation in Hansen diagrams revealed very similar profiles of Cerasome electrokinetic chromatography retention factors and skin permeability coefficients. In both cases, the characteristic pattern with two clusters of highly retained or highly permeable substances could be shown to be mainly caused by two groups of compounds, one of them with high affinity to ceramides, fatty acids and lecithin and the other being more affine to cholesterol. If based on a sufficiently comprehensive experimental dataset, model-independent predictions of skin permeability data using three-component Hansen solubility parameters are able to achieve similar accuracy as calculations made with an Abraham linear free energy relationship model in which the compounds are characterized by seven physicochemical descriptors

A Cascade Neural Network Architecture investigating Surface Plasmon Polaritons propagation for thin metals in OpenMP

Surface plasmon polaritons (SPPs) confined along metal-dielectric interface have attracted a relevant interest in the area of ultracompact photonic circuits, photovoltaic devices and other applications due to their strong field confinement and enhancement. This paper investigates a novel cascade neural network (NN) architecture to find the dependance of metal thickness on the SPP propagation. Additionally, a novel training procedure for the proposed cascade NN has been developed using an OpenMP-based framework, thus greatly reducing training time. The performed experiments confirm the effectiveness of the proposed NN architecture for the problem at hand

「問題導向學習」教案之品質改善：香港大學醫學院一年級生之經驗與回饋

To improve the quality of paper cases used for problem-based learning in the medical curriculum of the University of Hong Kong, Year 1 students were asked at the end of the year to fill in a questionnaire which addresses specific issues related to problem based learning. In addition, for each of the 6 new cases of PBL which were introduced into the first year, tutorials groups were asked to rate which of the learning objectives as specified in the cased were covered under the 4 themes: Biology of Health and Disease (Knowledge Component); Doctors and Patients (Clinical and communication Skills); Medicine and the Community (Societal and Population Medicine) and Professional Development (Medical Ethics and Law). Over eighty percent of the students found the PBL process to facilitate self directed learning and contributed to their learning. Over forty percent found there was unequal representation of the 4 themes with the issue of Professional Development to be the most inadequately covered. Various factors can be identified for the under representation and inadequate coverage of professional development issues. Possible solutions may include case modifications to ensure a fairer balance of 4 themes, alternative formats of enhancing the discussion of professional development issues, tutor training and coaching the students to address professional development issues

Game-based training of selective voluntary motor control in children and youth with upper motor neuron lesions: protocol for a multiple baseline design study

Background Impairments of selective control of joint movements can have consequences for many activities of daily life, but there are only a few interventions to improve selective voluntary motor control (SVMC). We have developed a treatment option to specifically enhance SVMC exploiting the advantages of interactive computer play technology. It targets SVMC by training selective activation of a muscle or a selective joint movement while it provides immediate feedback about involuntary muscle activations/movements at an (unwanted) joint. This study aims to investigate the effectiveness of this game-based intervention to enhance SVMC in children and youth with upper motor neuron lesions. Methods We will conduct a randomized, non-concurrent, multiple baseline design study. Patients aged between 6 and 20 years with reduced SVMC due to an upper motor neuron lesion will be included. During the baseline phase of random length, participants will attend their regular intensive rehabilitation program, and in the intervention phase, they will additionally complete 10 therapy sessions (à 40 min) of the game-based SVMC training. The primary outcome will be a short SVMC assessment conducted repeatedly throughout both phases, which quantifies movement accuracy and involuntary movements. Changes in clinical SVMC measures, muscle strength, cortical excitability, motor control of the inhibited/unwanted movement, and functional independence will be assessed as secondary outcomes. We will use a mixed-effect model to determine the change in the course of the primary outcome when the intervention is introduced, and we will compare changes between phases for secondary outcomes with paired tests. Discussion This study will provide first evidence whether SVMC can be improved with our game-based training. The single-case design takes into account the individualization required for this intervention, and it can help to address the challenges of intervention trials in our setting. Trial registration German Clinical Trials Register: DRKS00025184, registered on 28.04.2021

Playfully Assessing Lower Extremity Selective Voluntary Motor Control in Children With Cerebral Palsy: Psychometric Study

Background Objective measures specifically assessing selective voluntary motor control are scarce. Therefore, we have developed an interval-scaled assessment based on accelerometers. Objective This study provided a preliminary evaluation of the validity and reliability of this novel gamelike assessment measuring lower limb selective voluntary motor control in children with cerebral palsy (CP). Methods Children with CP and their neurologically intact peers were recruited for this psychometric evaluation of the assessgame. The participants played the assessgame and steered an avatar by selective hip, knee, or ankle joint movements captured with accelerometers. The assessgame’s scores provide information about the accuracy of the selective movement of the target joint and the amplitude and frequency of involuntary movements occurring in uninvolved joints. We established discriminative validity by comparing the assessgame scores of the children with CP with those of the neurologically intact children, concurrent validity by correlations with clinical scores and therapists’ opinions, and relative and absolute test-retest reliability. Results We included 20 children with CP (mean age 12 years and 5 months, SD 3 years and 4 months; Gross Motor Function Classification System levels I to IV) and 31 neurologically intact children (mean age 11 years and 1 month, SD 3 years and 6 months). The assessgame could distinguish between the children with CP and neurologically intact children. The correlations between the assessgame’s involuntary movement score and the therapist’s rating of the occurrence of involuntary movements during the game were moderate (Spearman ρ=0.56; P=.01), whereas the correlations of the assessgame outcomes with the Selective Control Assessment of the Lower Extremity and Gross Motor Function Classification System were low and not significant (|ρ|≤0.39). The intraclass correlation coefficients were >0.85 and indicated good relative test-retest reliability. Minimal detectable changes amounted to 25% (accuracy) and 44% (involuntary movement score) of the mean total scores. The percentage of children able to improve by the minimal detectable change without reaching the maximum score was 100% (17/17) for the accuracy score and 94% (16/17) for the involuntary movement score. Conclusions The assessgame proved reliable and showed discriminative validity in this preliminary evaluation. Concurrent validity was moderate with the therapist’s opinion but relatively poor with the Selective Control Assessment of the Lower Extremity. We assume that the assessment’s gamelike character demanded various other motor control aspects that are less considered in current clinical assessments

Validity and reliability of an accelerometer-based assessgame to quantify upper limb selective voluntary motor control

From Springer Nature via Jisc Publications RouterIntroduction: Current clinical assessments measure selective voluntary motor control (SVMC) on an ordinal scale. We introduce a playful, interval-scaled method to assess SVMC in children with brain lesions and evaluate its validity and reliability. Methods: Thirty-one neurologically intact children (median [1st-3rd quartile]: 11.6 years [8.5–13.9]) and 33 patients (12.2 years [8.8–14.9]) affected by upper motor neuron lesions with mild to moderate impairments participated. Using accelerometers, they played a movement tracking game (assessgame) with isolated joint movements (shoulder, elbow, lower arm [pro−/supination], wrist, and fingers), yielding an accuracy score. Involuntary movements were recorded simultaneously and resulted in an involuntary movement score. Both scores were normalized to the performance of 33 neurologically intact adults (32.5 years [27.9; 38.3]), which represented physiological movement patterns. We correlated the assessgame outcomes with the Manual Ability Classification System, Selective Control of the Upper Extremity Scale, and a therapist rating of involuntary movements. Furthermore, a robust ANCOVA was performed with age as covariate, comparing patients to their healthy peers at the age levels of 7.5, 9, 10.5, 12, and 15 years. Intraclass correlation coefficients and smallest real differences indicated relative and absolute reliability. Results: Correlations (Kendall/Spearman) for the accuracy score were τ = 0.29 (p = 0.035; Manual Ability Classification System), ρ = − 0.37 (p = 0.035; Selective Control of the Upper Extremity Scale), and ρ = 0.64 (p < 0.001; therapist rating). Correlations for the involuntary movement metric were τ = 0.37 (p = 0.008), ρ = − 0.55 (p = 0.001), and ρ = 0.79 (p < 0.001), respectively. The robust ANCOVAs revealed that patients performed significantly poorer than their healthy peers in both outcomes and at all age levels except for the dominant/less affected arm, where the youngest age group did not differ significantly. Robust intraclass correlation coefficients and smallest real differences were 0.80 and 1.02 (46% of median patient score) for the accuracy and 0.92 and 2.55 (58%) for involuntary movements, respectively. Conclusion: While this novel assessgame is valid, the reliability might need to be improved. Further studies are needed to determine whether the assessgame is sensitive enough to detect changes in SVMC after a surgical or therapeutic intervention.pubpu

Diffractive beam splitter characterization via a power-recycled interferometer

We used the high-precision laser interferometer technique of power recycling to characterize the optical loss of an all-reflective grating beam splitter. This beam splitter was used to set up a Michelson interferometer with a power-recycling resonator with a finesse of 883. Analyzing the results obtained, we determined the beam splitter's total optical loss to be (0.193+/-0.019)%. Low loss all-reflective beam splitters might find application in future high-power laser interferometers for the detection of gravitational waves