A facile system to evaluate in vitro drug release from dissolving microneedle arrays

The use of biological tissues in the in vitro assessments of dissolving (?) microneedle (MN) array mechanical strength and subsequent drug release profiles presents some fundamental difficulties, in part due to inherent variability of the biological tissues employed. As a result, these biological materials are not appropriate for routine used in industrial formulation development or quality control (QC) tests. In the present work a facile system using Parafilm M® (PF) to test drug permeation performance using dissolving MN arrays is proposed. Dissolving MN arrays containing 196 needles (600 μm needle height) were inserted into a single layer of PF and a hermetic “pouch” was created including the array inside. The resulting system was placed in a dissolution bath and the release of model molecules was evaluated. Different MN formulations were tested using this novel setup, releasing between 40 and 180 µg of their cargos after 6 hours. The proposed system is a more realistic approach for MN testing than the typical performance test described in the literature for conventional transdermal patches. Additionally, the use of PF membrane was tested either in the hermetic “pouch” and using Franz Cell methodology yielding comparable release curves. Microscopy was used in order to ascertain the insertion of the different MN arrays in the PF layer. The proposed system appears to be a good alternative to the use of Franz cells in order to compare different MN formulations. Given the increasing industrial interest in MN technology, the proposed system has potential as a standardised drug/active agent release test for quality control purposes.

PicSOr - An objective test of perceptual skill that predicts laparoscopic technical skill in three initial studies of laparoscopic performance

Background: Laparoscopic surgery requires surgeons to infer the shape of 3-D structures, such as the internal organs of patients, from 2-D displays on a video monitor. Recent evidence indicates that the issue is not resolved by the use of contemporary 3-D camera systems. It is therefore crucial to find ways of measuring differences in aptitude for recovering 3-D structure from 2-D images, and assessing its impact on performance. Our aim was to test empirically for a relationship between laparoscopic ability and the perceptual skill of recovering information about 3-D structures from 2-D monitor displays.

The performance of concrete exposed to marine environments: predictive modelling and use of laboratory/on site test methods

This paper reports an approach by which laboratory based testing and numerical modelling can be combined to predict the long term performance of a range of concretes exposed to marine environments. Firstly, a critical review of the test methods for assessing the chloride penetration resistance of concrete is given. The repeatability of the different test results is also included. In addition to the test methods, a numerical simulation model is used to explore the test data further to obtain long-term chloride ingress trends. The combined use of testing and modelling is validated with the help of long-term chloride ingress data from a North Sea exposure site. In summary, the paper outlines a methodology for determining the long term performance of concrete in marine environments.

A durability performance-index for concrete: developments in a novel test method

Implementation of both design for durability and performance-based standards and specifications are limited by the lack of rapid, simple, science based test methods for characterising the transport properties and deterioration resistance of concrete. This paper presents developments in the application of electrical property measurements as a testing methodology to evaluate the relative performance of a range of concrete mixes. The technique lends itself to in-situ monitoring thereby allowing measurements to be obtained on the as-placed concrete. Conductivity measurements are presented for concretes with and without supplementary cementitious materials (SCM’s) from demoulding up to 350 days. It is shown that electrical conductivity measurements display a continual decrease over the entire test period and attributed to pore structure refinement due to hydration and pozzolanic reaction. The term formation factor is introduced to rank concrete performance in terms of is resistance to chloride penetration.

Novel ketone diet enhances physical and cognitive performance

Ketone bodies are the most energy-efficient fuel and yield more ATP per mole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, low-carbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson's disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)-3-hydroxybutyl (R)-3-hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a treadmill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palm oil (P < 0.05). Ketone-fed rats completed an 8-arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P < 0.05). Isolated, perfused hearts from rats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [(31)P]-NMR spectroscopy. The novel ketone diet, therefore, improved physical performance and cognitive function in rats, and its energy-sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.

Drivetrain Effects on Small Engine Performance

Presented is a study that expands the body of knowledge on the effect of in-cycle speed fluctuations on performance of small engines. It uses the methods developed previously by Callahan, et al. (1) to examine a variety of two-stroke engines and one four-stroke engine. The two-stroke engines were: a high performance single-cylinder, a low performance single-cylinder, a high performance multi-cylinder, and a medium performance multi-cylinder. The four-stroke engine was a high performance single-cylinder unit. Each engine was modeled in Virtual Engines, which is a fully detailed one-dimensional thermodynamic engine simulator. Measured or predicted in-cycle speed data were input into the engine models. Predicted performance changes due to drivetrain effects are shown in each case, and conclusions are drawn from those results. The simulations for the high performance single-cylinder two-stroke engine predicted significant in-cycle crankshaft speed fluctuation amplitudes and significant changes in performance when the fluctuations were input into the engine model. This was validated experimentally on a firing test engine based on a Yamaha YZ250. The four-stroke engine showed significant changes in predicted performance compared to the prediction with zero speed fluctuation assumed in the model. Measured speed fluctuations from a firing Yamaha YZ400F engine were applied to the simulation in addition to data from a simple free mass model. Both methods predicted similar fluctuation profiles and changes in performance. It is shown that the gear reduction between the crankshaft and clutch allowed for this similar behavior. The multi-cylinder, high performance two-stroke engine also showed significant changes in performance, in this case depending on the firing configuration. The low output two-stroke engine simulation showed only a negligible change in performance in spite of high amplitude speed fluctuations. This was due to its flat torque versus speed characteristic. The medium performance multi-cylinder two-stroke engine also showed only a negligible change in performance, in this case due to a relatively high inertia rotating assembly and multiple cylinder firing events within the revolution. These smoothed the net torque pulsations and reduced the amplitude of the speed fluctuation itself.

Directional performance in motion transparency

Motion transparency provides a challenging test case for our understanding of how visual motion, and other attributes, are computed and represented in the brain. However, previous studies of visual transparency have used subjective criteria which do not confirm the existence of independent representations of the superimposed motions. We have developed measures of performance in motion transparency that require observers to extract information about two motions jointly, and therefore test the information that is simultaneously represented for each motion. Observers judged whether two motions were at 90 to one another; the base direction was randomized so that neither motion taken alone was informative. The precision of performance was determined by the standard deviations (S.D.s) of probit functions fitted to the data. Observers also made judgments of orthogonal directions between a single motion stream and a line, for one of two transparent motions against a line and for two spatially segregated motions. The data show that direction judgments with transparency can be made with comparable accuracy to segregated (non-transparent) conditions, supporting the idea that transparency involves the equivalent representation of two global motions in the same region. The precision of this joint direction judgment is, however, 2–3 times poorer than that for a single motion stream. The precision in directional judgment for a single stream is reduced only by a factor of about 1.5 by superimposing a second stream. The major effect in performance, therefore, appears to be associated with the need to compute and compare two global representations of motion, rather than with interference between the dot streams per se. Experiment 2tested the transparency of motions separated by a range of angles from 5 to 180 by requiring subjects to set a line matching the perceived direction of each motion. The S.D.s of these settings demonstrated that directions of transparent motions were represented independently for separations over 20. Increasing dot speeds from 1 to 10 deg/s improved directional performance but had no effect on transparency perception. Transparency was also unaffected by variations of density between 0.1 and 19 dots/deg2

Performance Management in the UK Public Sector: addressing multiple stakeholder complexity

Purpose The aim of this paper is to explore the issues involved in developing and applying performance management approaches within a large UK public sector department using a multiple stakeholder perspective and an accompanying theoretical framework. Design/methodology/approach An initial short questionnaire was used to determine perceptions about the implementation and effectiveness of the new performance management system across the organisation. In total, 700 questionnaires were distributed. Running concurrently with an ethnographic approach, and informed by the questionnaire responses, was a series of semi-structured interviews and focus groups. Findings Staff at all levels had an understanding of the new system and perceived it as being beneficial. However, there were concerns that the approach was not continuously managed throughout the year and was in danger of becoming an annual event, rather than an ongoing process. Furthermore, the change process seemed to have advanced without corresponding changes to appraisal and reward and recognition systems. Thus, the business objectives were not aligned with motivating factors within the organisation. Research limitations/implications Additional research to test the validity and usefulness of the theoretical model, as discussed in this paper, would be beneficial. Practical implications The strategic integration of the stakeholder performance measures and scorecards was found to be essential to producing an overall stakeholder-driven strategy within the case study organisation. Originality/value This paper discusses in detail the approach adopted and the progress made by one large UK public sector organisation, as it attempts to develop better relationships with all of its stakeholders and hence improve its performance. This paper provides a concerted attempt to link theory with practice.

Comparison of LIMPET contra-rotating wells turbine with theoretical and model test predictions

The performance of the contra-rotating Wells turbine installed in the LIMPET wave power station is compared to the predicted performance from theoretical analysis and model tests. A reasonable agreement was found between the predicted and measured turbine damping characteristic, however the turbine efficiency was found to be poorly predicted. It is postulated that this is due to the unsteady nature and mal-distribution of flow through the LIMPET turbine, which were not considered in the predictions. It is suggested that the reduced performance of the contra-rotating Wells turbine makes biplane or monoplane Wells turbines with guide vanes better solutions for OWC's.

Errorless learning and memory performance in schizophrenia

There is evidence that patients with schizophrenia have impaired explicit memory and intact implicit memory. The present study sought to replicate and extend that of O'Carroll et al. [O'Carroll, R.E., Russell, H.H., Lawrie, S.M. and Johnstone, E.C., 1999. Errorless learning and the cognitive rehabilitation of memory-impaired schizophrenic patients. Psychological Medicine 29, 105-112.] which reported that for memory-impaired patients with schizophrenia performance on a (cued) word recall task is enhanced using errorless learning techniques (in which errors are prevented during learning) compared to errorful learning (the traditional trial-and-error approach). Thirty patients with a DSM-IV diagnosis of schizophrenia and fifteen healthy controls (HC) participated. The Rivermead Behavioural Memory Test was administered and from their scores, the schizophrenic patients were classified as either memory-impaired (MIS), or memory-unimpaired (MUS). During the training phase two lists of words were learned separately, one using the errorless learning approach and the other using an errorful approach. Subjects were then tested for their recall of the words using cued recall. After errorful learning training, performance on word recall for the MIS group was impaired compared to the MUS and HC groups. However, after errorless learning training, no significant differences in performance were found between the three groups. Errorless learning may play an important role in remediation of cognitive deficits for patients with schizophrenia. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Modelling the performance of self-compacting SIFCON of cement slurries containing limestone powder using genetic programming technique

The paper explores the potential of applicability of Genetic programming approach (GP), adopted in this investigation, to model the combined effects of five independent variables to predict the mini-slump, the plate cohesion meter, the induced bleeding test, the J-fiber penetration value, and the compressive strength at 7 and 28 days of self-compacting slurry infiltrated fiber concrete (SIFCON). The variables investigated were the proportions of limestone powder (LSP) and sand, the dosage rates of superplasticiser (SP) and viscosity modifying agent (VMA), and water-to-binder ratio (W/B). Twenty eight mixtures were made with 10-50% LSP as replacement of cement, 0.02-0.06% VMA by mass of cement, 0.6-1.2% SP and 50-150% sand (% mass of binder) and 0.42-0.48 W/B. The proposed genetic models of the self-compacting SIFCON offer useful modelling approach regarding the mix optimisation in predicting the fluidity, the cohesion, the bleeding, the penetration, and the compressive strength.