Evaluation of drug physical form during granulation, tabletting and storage

An active pharmaceutical ingredient (API) was found to dissociate from the highly crystalline hydrochloride form to the amorphous free base form, with consequent alterations to tablet properties. Here, a wet granulation manufacturing process has been investigated using in situ Fourier transform (FT)-Raman spectroscopic analyses of granules and tablets prepared with different granulating fluids and under different manufacturing conditions. Dosage form stability under a range of storage stresses was also investigated. Despite the spectral similarities between the two drug forms, low levels of API dissociation could be quantified in the tablets; the technique allowed discrimination of around 4% of the API content as the amorphous free base (i.e. less than 1% of the tablet compression weight). API dissociation was shown to be promoted by extended exposure to moisture. Aqueous granulating fluids and manufacturing delays between granulation and drying stages and storage of the tablets in open conditions at 40◦C/75% relative humidity (RH) led to dissociation. In contrast, non-aqueous granulating fluids, with no delay in processing and storage of the tablets in either sealed containers or at lower temperature/humidity prevented detectable dissociation. It is concluded that appropriate manufacturing process and storage conditions for the finished product involved minimising exposure to moisture of the API. Analysis of the drug using FT-Raman spectroscopy allowed rapid optimisation of the process whilst offering quantitative molecular information concerning the dissociation of the drug salt to the amorphous free base form.

Experience and real estate investment decision-making: a process-tracing investigation

This study investigates the impact of experience upon trained behaviours in real estate investment decision‐making. In a controlled experiment design, two groups of subjects, experts and novices, conduct an evaluation and reach a decision about two investment options. Using a process‐tracing technique, each subject’s behaviour is observed and recorded. Differences between the groups are discovered in relation to some behaviour characteristics, but experience appears not to impact all behaviours. These findings are discussed in relation to the current absence of a universal normative model of real estate investment decision‐making. In an associated component of the study, the belief that monetary compensation is needed in order to render valid results from studies such as this is tested. We find this not to be the case.

Natural caprine whey oligosaccharides separated by membrane technology and profile evaluation by capillary electrophoresis

The functional food market is growing rapidly and membrane processing offers several advantages over conventional methods for separation, fractionation and recovery of bioactive components. The aim of the present study was to select a process that could be implemented easily on an industrial scale for the isolation of natural lactose-derived oligosaccharides (OS) from caprine whey, enabling the development of functional foods for clinical and infant nutrition. The most efficient process was the combination of a pre-treatment to eliminate proteins and fat, using an ultrafiltration (UF) membrane of 25 kDa molecular weight cut off (MWCO), followed by a tighter UF membrane with 1 kDa MWCO. Circa 90% of the carbohydrates recovered in the final retentate were OS. Capillary electrophoresis was used to evaluate the OS profile in this retentate. The combined membrane-processing system is thus a promising technique for obtaining natural concentrated OS from whey. Powered

Evaluation of Earth system models using modern and palaeo-observations: the state-of-the-art

Earth system models are increasing in complexity and incorporating more processes than their predecessors, making them important tools for studying the global carbon cycle. However, their coupled behaviour has only recently been examined in any detail, and has yielded a very wide range of outcomes, with coupled climate-carbon cycle models that represent land-use change simulating total land carbon stores by 2100 that vary by as much as 600 Pg C given the same emissions scenario. This large uncertainty is associated with differences in how key processes are simulated in different models, and illustrates the necessity of determining which models are most realistic using rigorous model evaluation methodologies. Here we assess the state-of-the-art with respect to evaluation of Earth system models, with a particular emphasis on the simulation of the carbon cycle and associated biospheric processes. We examine some of the new advances and remaining uncertainties relating to (i) modern and palaeo data and (ii) metrics for evaluation, and discuss a range of strategies, such as the inclusion of pre-calibration, combined process- and system-level evaluation, and the use of emergent constraints, that can contribute towards the development of more robust evaluation schemes. An increasingly data-rich environment offers more opportunities for model evaluation, but it is also a challenge, as more knowledge about data uncertainties is required in order to determine robust evaluation methodologies that move the field of ESM evaluation from "beauty contest" toward the development of useful constraints on model behaviour.

Development and evaluation of an Earth-System model – HadGEM2

We describe here the development and evaluation of an Earth system model suitable for centennial-scale climate prediction. The principal new components added to the physical climate model are the terrestrial and ocean ecosystems and gas-phase tropospheric chemistry, along with their coupled interactions. The individual Earth system components are described briefly and the relevant interactions between the components are explained. Because the multiple interactions could lead to unstable feedbacks, we go through a careful process of model spin up to ensure that all components are stable and the interactions balanced. This spun-up configuration is evaluated against observed data for the Earth system components and is generally found to perform very satisfactorily. The reason for the evaluation phase is that the model is to be used for the core climate simulations carried out by the Met Office Hadley Centre for the Coupled Model Intercomparison Project (CMIP5), so it is essential that addition of the extra complexity does not detract substantially from its climate performance. Localised changes in some specific meteorological variables can be identified, but the impacts on the overall simulation of present day climate are slight. This model is proving valuable both for climate predictions, and for investigating the strengths of biogeochemical feedbacks.

Evaluation of biospheric components in Earth system models using modern and palaeo-observations: the state-of-the-art

Earth system models (ESMs) are increasing in complexity by incorporating more processes than their predecessors, making them potentially important tools for studying the evolution of climate and associated biogeochemical cycles. However, their coupled behaviour has only recently been examined in any detail, and has yielded a very wide range of outcomes. For example, coupled climate–carbon cycle models that represent land-use change simulate total land carbon stores at 2100 that vary by as much as 600 Pg C, given the same emissions scenario. This large uncertainty is associated with differences in how key processes are simulated in different models, and illustrates the necessity of determining which models are most realistic using rigorous methods of model evaluation. Here we assess the state-of-the-art in evaluation of ESMs, with a particular emphasis on the simulation of the carbon cycle and associated biospheric processes. We examine some of the new advances and remaining uncertainties relating to (i) modern and palaeodata and (ii) metrics for evaluation. We note that the practice of averaging results from many models is unreliable and no substitute for proper evaluation of individual models. We discuss a range of strategies, such as the inclusion of pre-calibration, combined process- and system-level evaluation, and the use of emergent constraints, that can contribute to the development of more robust evaluation schemes. An increasingly data-rich environment offers more opportunities for model evaluation, but also presents a challenge. Improved knowledge of data uncertainties is still necessary to move the field of ESM evaluation away from a "beauty contest" towards the development of useful constraints on model outcomes.

An introduction to the Chinese Evaluation Standard for the indoor thermal environment

Designing for indoor thermal environmental conditions is one of the key elements in the energy efficient building design process. This paper introduces a development of the Chinese national Evaluation Standard for indoor thermal environments (Evaluation Standard). International standards including the ASHRAE55, ISO7730, DIN EN, and CIBSE Guide-A have been reviewed and referenced for the development of the Evaluation Standard. In addition, over 28,000 subjects participated in the field study from different climate zones in China and over 500 subjects have been involved in laboratory studies. The research findings reveal that there is a need to update the Chinese thermal comfort standard based on local climates and people's habitats. This paper introduces in detail the requirements for the thermal environment for heated and cooled buildings and free-running buildings in China.

Evaluation of boundary-layer type in a weather forecast model utilising long-term Doppler lidar observations

Many studies evaluating model boundary-layer schemes focus either on near-surface parameters or on short-term observational campaigns. This reflects the observational datasets that are widely available for use in model evaluation. In this paper we show how surface and long-term Doppler lidar observations, combined in a way to match model representation of the boundary layer as closely as possible, can be used to evaluate the skill of boundary-layer forecasts. We use a 2-year observational dataset from a rural site in the UK to evaluate a climatology of boundary layer type forecast by the UK Met Office Unified Model. In addition, we demonstrate the use of a binary skill score (Symmetric Extremal Dependence Index) to investigate the dependence of forecast skill on season, horizontal resolution and forecast leadtime. A clear diurnal and seasonal cycle can be seen in the climatology of both the model and observations, with the main discrepancies being the model overpredicting cumulus capped and decoupled stratocumulus capped boundary-layers and underpredicting well mixed boundary-layers. Using the SEDI skill score the model is most skillful at predicting the surface stability. The skill of the model in predicting cumulus capped and stratocumulus capped stable boundary layer forecasts is low but greater than a 24 hr persistence forecast. In contrast, the prediction of decoupled boundary-layers and boundary-layers with multiple cloud layers is lower than persistence. This process based evaluation approach has the potential to be applied to other boundary-layer parameterisation schemes with similar decision structures.

Consumers perception and evaluation of fresh cut buying attributes: a survey on the Italian market

During the last twenty years, consumer choice in high income countries is no longer merely dictated by price and the organoleptic characteristics of a product, but also by other features some of which are not patently tangible. The growing importance of such attributes in the process of consumer choice is not only due to income increase, but also to changes in lifestyle such as migrations from the countryside, a generalized urbanization and consequential city life style, female emancipation and work outside the domestic walls for women, the drastic decrease in hard physical labor and the process of internationalization. The present survey study aims to explore the importance that Italian consumers give to fresh cut buying attributes and which of these attributes should be taken into consideration by industries in order to satisfy the needs of the most critical shoppers. Where possible, market and survey data for fresh cut products will be compared with those for cooked products and before presenting the results and conclusions of the study, the technical issues of processing will be highlighted owing to the fact that they affect the marketing of these products, the recent market situation with regard to consumption will be illustrated and the methodology used will be described.

Calibration and evaluation of individual-based models using Approximate Bayesian Computation

This paper investigates the feasibility of using approximate Bayesian computation (ABC) to calibrate and evaluate complex individual-based models (IBMs). As ABC evolves, various versions are emerging, but here we only explore the most accessible version, rejection-ABC. Rejection-ABC involves running models a large number of times, with parameters drawn randomly from their prior distributions, and then retaining the simulations closest to the observations. Although well-established in some fields, whether ABC will work with ecological IBMs is still uncertain. Rejection-ABC was applied to an existing 14-parameter earthworm energy budget IBM for which the available data consist of body mass growth and cocoon production in four experiments. ABC was able to narrow the posterior distributions of seven parameters, estimating credible intervals for each. ABC’s accepted values produced slightly better fits than literature values do. The accuracy of the analysis was assessed using cross-validation and coverage, currently the best available tests. Of the seven unnarrowed parameters, ABC revealed that three were correlated with other parameters, while the remaining four were found to be not estimable given the data available. It is often desirable to compare models to see whether all component modules are necessary. Here we used ABC model selection to compare the full model with a simplified version which removed the earthworm’s movement and much of the energy budget. We are able to show that inclusion of the energy budget is necessary for a good fit to the data. We show how our methodology can inform future modelling cycles, and briefly discuss how more advanced versions of ABC may be applicable to IBMs. We conclude that ABC has the potential to represent uncertainty in model structure, parameters and predictions, and to embed the often complex process of optimizing an IBM’s structure and parameters within an established statistical framework, thereby making the process more transparent and objective.

Dehydrodipeptide hydrogelators containing naproxen N‑Capped tryptophan: self-assembly, hydrogel characterization, and evaluation as potential drug nanocarriers

In this work, we introduce dipeptides containing tryptophan N-capped with the nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids, dehydrophenylalanine (ΔPhe), dehydroaminobutyric acid (ΔAbu), and dehydroalanine (ΔAla) as efficacious protease resistant hydrogelators. Optimized conditions for gel formation are reported. Transmission electron microscopy experiments revealed that the hydrogels consist of networks of micro/nanosized fibers formed by peptide self-assembly. Fluorescence and circular dichroism spectroscopy indicate that the self-assembly process is driven by stacking interactions of the aromatic groups. The naphthalene groups of the naproxen moieties are highly organized in the fibers through chiral stacking. Rheological experiments demonstrated that the most hydrophobic peptide (containing C-terminal ΔPhe) formed more elastic gels at lower critical gelation concentrations. This gel revealed irreversible breakup, while the C-terminal ΔAbu and ΔAla gels, although less elastic, exhibited structural recovery and partial healing of the elastic properties. A potential antitumor thieno[3,2-b]pyridine derivative was incorporated (noncovalently) into the gel formed by the hydrogelator containing C-terminal ΔPhe residue. Fluorescence and Förster resonance energy transfer measurements indicate that the drug is located in a hydrophobic environment, near/associated with the peptide fibers, establishing this type of hydrogel as a good drug-nanocarrier candidate.

Design and techno-economic evaluation of microbial oil production as a renewable resource for biodiesel and oleochemical production

Experimental results from the open literature have been employed for the design and techno-economic evaluation of four process flowsheets for the production of microbial oil or biodiesel. The fermentation of glucose-based media using the yeast strain Rhodosporidium toruloides has been considered. Biodiesel production was based on the exploitation of either direct transesterification (without extraction of lipids from microbial biomass) or indirect transesterifaction of extracted microbial oil. When glucose-based renewable resources are used as carbon source for an annual production capacity of 10,000 t microbial oil and zero cost of glucose (assuming development of integrated biorefineries in existing industries utilising waste or by-product streams) the estimated unitary cost of purified microbial oil is $3.4/kg. Biodiesel production via indirect transesterification of extracted microbial oil proved more cost-competitive process compared to the direct conversion of dried yeast cells. For a price of glucose of $400/t oil production cost and biodiesel production cost are estimated to be $5.5/kg oil and $5.9/kg biodiesel, correspondingly. Industrial implementation of microbial oil production from oleaginous yeast is strongly dependent on the feedstock used and on the fermentation stage where significantly higher productivities and final microbial oil concentrations should be achieved.

Using developmental evaluation methods with communities of practice

Purpose This research explored the use of developmental evaluation methods with community of practice programmes experiencing change or transition to better understand how to target support resources. Design / methodology / approach The practical use of a number of developmental evaluation methods was explored in three organisations over a nine month period using an action research design. The research was a collaborative process involving all the company participants and the academic (the author) with the intention of developing the practices of the participants as well as contributing to scholarship. Findings The developmental evaluation activities achieved the objectives of the knowledge managers concerned: they developed a better understanding of the contribution and performance of their communities of practice, allowing support resources to be better targeted. Three methods (fundamental evaluative thinking, actual-ideal comparative method and focus on strengths and assets) were found to be useful. Cross-case analysis led to the proposition that developmental evaluation methods act as a structural mechanism that develops the discourse of the organisation in ways that enhance the climate for learning, potentially helping develop a learning organization. Practical implications Developmental evaluation methods add to the options available to evaluate community of practice programmes. These supplement the commonly used activity indicators and impact story methods. 2 Originality / value Developmental evaluation methods are often used in social change initiatives, informing public policy and funding decisions. The contribution here is to extend their use to organisational community of practice programmes.