Novel polyvinylpyrrolidones to improve delivery of poorly-water soluble drugs; from design to synthesis and evaluation

Polyvinylpyrrolidone is a widely used in tablet formulations with the linear form acting as a wetting agent and disintegrant whereas the cross-linked form is a super-disintegrant. We have previously reported that simply mixing the commercial cross-linked polymer with ibuprofen disrupted drug crystallinity with consequent improvements in drug dissolution behavior. In this study, we have designed and synthesized novel cross-linking agents containing a range of oligoether moieties which have then be polymerized with vinylpyrrolidone to generate a suite of novel excipients with enhanced hydrogen-bonding capabilities. The polymers have a porous surface and swell in most common solvents and in water; properties which suggest their value as disintegrants. The polymers were evaluated in simple physical mixtures with ibuprofen as a model poorly-water soluble drug. The results show that the novel PVPs induce the drug to become “X-ray amorphous”, which increased dissolution to a greater extent than that seen with commercial cross-linked PVP. The polymers stabilize the amorphous drug with no evidence for recrystallization seen after 20 weeks storage.

An evaluation of the spatiotemporal structure of large-scale European drought within the HiGEM climate model

We compare the characteristics of synthetic European droughts generated by the HiGEM1 coupled climate model run with present day atmospheric composition with observed drought events extracted from the CRU TS3 data set. The results demonstrate consistency in both the rate of drought occurrence and the spatiotemporal structure of the events. Estimates of the probability density functions for event area, duration and severity are shown to be similar with confidence > 90%. Encouragingly, HiGEM is shown to replicate the extreme tails of the observed distributions and thus the most damaging European drought events. The soil moisture state is shown to play an important role in drought development. Once a large-scale drought has been initiated it is found to be 50% more likely to continue if the local soil moisture is below the 40th percentile. In response to increased concentrations of atmospheric CO2, the modelled droughts are found to increase in duration, area and severity. The drought response can be largely attributed to temperature driven changes in relative humidity. 1 HiGEM is based on the latest climate configuration of the Met Office Hadley Centre Unified Model (HadGEM1) with the horizontal resolution increased to 1.25 x 0.83 degrees in longitude and latitude in the atmosphere and 1/3 x 1/3 degrees in the ocean.

Novel management to enhance spider biodiversity in existing grass buffer strips

Grass buffer strips have been widely sown to mitigate against intensive agricultural management practices that have negatively impacted on invertebrate and plant biodiversity in arable farming systems. Typically, such strips are floristically species poor and are dominated by grasses. In the present study, we developed management practices to enhance the floristic and structural diversity of these existing strips for the benefit of spiders, a key provider of natural pest control in crops. Across three UK arable farms, we investigated the benefits of: (i) scarification to create germination niches into which wildflower seeds were sown and (ii) the effect of graminicide applications to suppress grass dominance. Spiders were sampled twice per year (July and September) during 2008 and 2009. The combination of scarification with wildflower seeds, as well as graminicide, resulted in the greatest wildflower cover and lowest grass cover, with a general trend of increased abundance of adult and juvenile spiders. The abundance of Pachygnatha degeeri, Bathyphantes gracilis and juvenile wolf spiders of the genus Pardosa was positively correlated with wildflower cover, probably reflecting increased prey availability. Sward structure was negatively correlated with Erigone atra, Oedothorax fuscus and juvenile Pardosa abundance. Management that utilizes existing commonly adopted agri-environment options, such as grass buffer strips, represents a potentially important conservation tool for increasing the quantity and quality of invertebrate habitats. This can maximize opportunities for the provision of multiple ecosystem services, including pest regulation by predators such as spiders. These management practices have the potential to be incorporated into existing U.K. and European agri-environment schemes.

Description and process evaluation of pharmacists’ interventions in a pharmacist-led information technology-enabled multicentre cluster randomised controlled trial for reducing medication errors in general practice (PINCER trial)

Objective To undertake a process evaluation of pharmacists' recommendations arising in the context of a complex IT-enabled pharmacist-delivered randomised controlled trial (PINCER trial) to reduce the risk of hazardous medicines management in general practices. Methods PINCER pharmacists manually recorded patients’ demographics, details of interventions recommended, actions undertaken by practice staff and time taken to manage individual cases of hazardous medicines management. Data were coded and double entered into SPSS v15, and then summarised using percentages for categorical data (with 95% CI) and, as appropriate, means (SD) or medians (IQR) for continuous data. Key findings Pharmacists spent a median of 20 minutes (IQR 10, 30) reviewing medical records, recommending interventions and completing actions in each case of hazardous medicines management. Pharmacists judged 72% (95%CI 70, 74) (1463/2026) of cases of hazardous medicines management to be clinically relevant. Pharmacists recommended 2105 interventions in 74% (95%CI 73, 76) (1516/2038) of cases and 1685 actions were taken in 61% (95%CI 59, 63) (1246/2038) of cases; 66% (95%CI 64, 68) (1383/2105) of interventions recommended by pharmacists were completed and 5% (95%CI 4, 6) (104/2105) of recommendations were accepted by general practitioners (GPs), but not completed at the end of the pharmacists’ placement; the remaining recommendations were rejected or considered not relevant by GPs. Conclusions The outcome measures were used to target pharmacist activity in general practice towards patients at risk from hazardous medicines management. Recommendations from trained PINCER pharmacists were found to be broadly acceptable to GPs and led to ameliorative action in the majority of cases. It seems likely that the approach used by the PINCER pharmacists could be employed by other practice pharmacists following appropriate training.

The integrated WRF/urban modelling system: development, evaluation, and applications to urban environmental problems

To bridge the gaps between traditional mesoscale modelling and microscale modelling, the National Center for Atmospheric Research, in collaboration with other agencies and research groups, has developed an integrated urban modelling system coupled to the weather research and forecasting (WRF) model as a community tool to address urban environmental issues. The core of this WRF/urban modelling system consists of the following: (1) three methods with different degrees of freedom to parameterize urban surface processes, ranging from a simple bulk parameterization to a sophisticated multi-layer urban canopy model with an indoor–outdoor exchange sub-model that directly interacts with the atmospheric boundary layer, (2) coupling to fine-scale computational fluid dynamic Reynolds-averaged Navier–Stokes and Large-Eddy simulation models for transport and dispersion (T&D) applications, (3) procedures to incorporate high-resolution urban land use, building morphology, and anthropogenic heating data using the National Urban Database and Access Portal Tool (NUDAPT), and (4) an urbanized high-resolution land data assimilation system. This paper provides an overview of this modelling system; addresses the daunting challenges of initializing the coupled WRF/urban model and of specifying the potentially vast number of parameters required to execute the WRF/urban model; explores the model sensitivity to these urban parameters; and evaluates the ability of WRF/urban to capture urban heat islands, complex boundary-layer structures aloft, and urban plume T&D for several major metropolitan regions. Recent applications of this modelling system illustrate its promising utility, as a regional climate-modelling tool, to investigate impacts of future urbanization on regional meteorological conditions and on air quality under future climate change scenarios. Copyright © 2010 Royal Meteorological Society

Aerosol indirect effects – general circulation model intercomparison and evaluation with satellite data

Aerosol indirect effects continue to constitute one of the most important uncertainties for anthropogenic climate perturbations. Within the international AEROCOM initiative, the representation of aerosol-cloud-radiation interactions in ten different general circulation models (GCMs) is evaluated using three satellite datasets. The focus is on stratiform liquid water clouds since most GCMs do not include ice nucleation effects, and none of the model explicitly parameterises aerosol effects on convective clouds. We compute statistical relationships between aerosol optical depth (τa) and various cloud and radiation quantities in a manner that is consistent between the models and the satellite data. It is found that the model-simulated influence of aerosols on cloud droplet number concentration (Nd ) compares relatively well to the satellite data at least over the ocean. The relationship between �a and liquid water path is simulated much too strongly by the models. This suggests that the implementation of the second aerosol indirect effect mainly in terms of an autoconversion parameterisation has to be revisited in the GCMs. A positive relationship between total cloud fraction (fcld) and �a as found in the satellite data is simulated by the majority of the models, albeit less strongly than that in the satellite data in most of them. In a discussion of the hypotheses proposed in the literature to explain the satellite-derived strong fcld–�a relationship, our results indicate that none can be identified as a unique explanation. Relationships similar to the ones found in satellite data between �a and cloud top temperature or outgoing long-wave radiation (OLR) are simulated by only a few GCMs. The GCMs that simulate a negative OLR - �a relationship show a strong positive correlation between �a and fcld. The short-wave total aerosol radiative forcing as simulated by the GCMs is strongly influenced by the simulated anthropogenic fraction of �a, and parameterisation assumptions such as a lower bound on Nd . Nevertheless, the strengths of the statistical relationships are good predictors for the aerosol forcings in the models. An estimate of the total short-wave aerosol forcing inferred from the combination of these predictors for the modelled forcings with the satellite-derived statistical relationships yields a global annual mean value of −1.5±0.5Wm−2. In an alternative approach, the radiative flux perturbation due to anthropogenic aerosols can be broken down into a component over the cloud-free portion of the globe (approximately the aerosol direct effect) and a component over the cloudy portion of the globe (approximately the aerosol indirect effect). An estimate obtained by scaling these simulated clearand cloudy-sky forcings with estimates of anthropogenic �a and satellite-retrieved Nd–�a regression slopes, respectively, yields a global, annual-mean aerosol direct effect estimate of −0.4±0.2Wm−2 and a cloudy-sky (aerosol indirect effect) estimate of −0.7±0.5Wm−2, with a total estimate of −1.2±0.4Wm−2.

A low-cost wireless temperature sensor: evaluation for use in environmental applications

With a wide range of applications benefiting from dense network air temperature observations but with limitations of costs, existing siting guidelines and risk of damage to sensors, new methods are required to gain a high resolution understanding of the spatio-temporal patterns of urban meteorological phenomena such as the urban heat island or precision farming needs. With the launch of a new generation of low cost sensors it is possible to deploy a network to monitor air temperature at finer spatial resolutions. Here we investigate the Aginova Sentinel Micro (ASM) sensor with a bespoke radiation shield (together < US$150) which can provide secure near-real-time air temperature data to a server utilising existing (or user deployed) Wireless Fidelity (Wi-Fi) networks. This makes it ideally suited for deployment where wireless communications readily exist, notably urban areas. Assessment of the performance of the ASM relative to traceable standards in a water bath and atmospheric chamber show it to have good measurement accuracy with mean errors < ± 0.22 °C between -25 and 30 °C, with a time constant in ambient air of 110 ± 15 s. Subsequent field tests of it within the bespoke shield also had excellent performance (root-mean-square error = 0.13 °C) over a range of meteorological conditions relative to a traceable operational UK Met Office platinum resistance thermometer. These results indicate that the ASM and bespoke shield are more than fit-for-purpose for dense network deployment in urban areas at relatively low cost compared to existing observation techniques.

Intercomparison and evaluation of global aerosol microphysical properties among AeroCom models of a range of complexity

Many of the next generation of global climate models will include aerosol schemes which explicitly simulate the microphysical processes that determine the particle size distribution. These models enable aerosol optical properties and cloud condensation nuclei (CCN) concentrations to be determined by fundamental aerosol processes, which should lead to a more physically based simulation of aerosol direct and indirect radiative forcings. This study examines the global variation in particle size distribution simulated by 12 global aerosol microphysics models to quantify model diversity and to identify any common biases against observations. Evaluation against size distribution measurements from a new European network of aerosol supersites shows that the mean model agrees quite well with the observations at many sites on the annual mean, but there are some seasonal biases common to many sites. In particular, at many of these European sites, the accumulation mode number concentration is biased low during winter and Aitken mode concentrations tend to be overestimated in winter and underestimated in summer. At high northern latitudes, the models strongly underpredict Aitken and accumulation particle concentrations compared to the measurements, consistent with previous studies that have highlighted the poor performance of global aerosol models in the Arctic. In the marine boundary layer, the models capture the observed meridional variation in the size distribution, which is dominated by the Aitken mode at high latitudes, with an increasing concentration of accumulation particles with decreasing latitude. Considering vertical profiles, the models reproduce the observed peak in total particle concentrations in the upper troposphere due to new particle formation, although modelled peak concentrations tend to be biased high over Europe. Overall, the multi-model-mean data set simulates the global variation of the particle size distribution with a good degree of skill, suggesting that most of the individual global aerosol microphysics models are performing well, although the large model diversity indicates that some models are in poor agreement with the observations. Further work is required to better constrain size-resolved primary and secondary particle number sources, and an improved understanding of nucleation and growth (e.g. the role of nitrate and secondary organics) will improve the fidelity of simulated particle size distributions.

Causes of plasma flow bursts and dayside auroral transients: An evaluation of two models Invoking reconnection pulses and changes in the Y component of the magnetosheath field

Longitudinal flow bursts observed by the European Incoherent Scatter (EISCAT) radar, in association with dayside auroral transients observed from Svalbard, have been interpreted as resulting from pulses of enhanced reconnection at the dayside magnetopause. However, an alternative model has recently been proposed for a steady rate of magnetopause reconnection, in which the bursts of longitudinal flow are due to increases in the field line curvature force, associated with the By component of the magnetosheath field. We here evaluate these two models, using observations on January 20, 1990, by EISCAT and a 630-nm all-sky camera at Ny Ålesund. For both models, we predict the behavior of both the dayside flows and the 630-nm emissions on newly opened field lines. It is shown that the signatures of steady reconnection and magnetosheath By changes could possibly resemble the observed 630-nm auroral events, but only for certain locations of the observing site, relative to the ionospheric projection of the reconnection X line: however, in such cases, the flow bursts would be seen between the 630-nm transients and not within them. On the other hand, the model of reconnection rate pulses predicts that the flows will be enhanced within each 630-nm transient auroral event. The observations on January 20, 1990, are shown to be consistent with the model of enhanced reconnection rate pulses over a background level and inconsistent with the effects of periodic enhancements of the magnitude of the magnetosheath By component. We estimate that the reconnection rate within the pulses would have to be at least an order of magnitude larger than the background level between the pulses.

Fabrication and evaluation of a skutterudite-based thermoelectric module for high-temperature applications

We report a straightforward methodology for the fabrication of high-temperature thermoelectric (TE) modules using commercially available solder alloys and metal barriers. This methodology employs standard and accessible facilities that are simple to implement in any laboratory. A TE module formed by nine n-type Yb x Co4Sb12 and p-type Ce x Fe3CoSb12 state-of-the-art skutterudite material couples was fabricated. The physical properties of the synthesized skutterudites were determined, and the module power output, internal resistance, and thermocycling stability were evaluated in air. At a temperature difference of 365 K, the module provides more than 1.5 W cm−3 volume power density. However, thermocycling showed an increase of the internal module resistance and degradation in performance with the number of cycles when the device is operated at a hot-side temperature higher than 573 K. This may be attributed to oxidation of the skutterudite thermoelements.

Love of reading: the evaluation of KidsREAD programme in Singapore

In Singapore about 20% of families are considered to be socio-economically disadvantaged. Children from these families have been identified as having reading difficulties when they enter primary school. Recognizing that children from these families have limited access to reading materials, the National Library Board, in partnership with local community clubs and family service centres, has established the KidsREAD literacy programme where volunteers, mostly university and college students, help children between 4 and 8 years of age overcome some of their reading problems. The KidsREAD clubs aim to “promote the love of reading and cultivate good reading habits among all young Singaporeans, in particular children from low-income families” (National Library Board, 2005). This paper presents an evaluation of the KidsREAD clubs with regard to children’s attitudes towards reading. It explores the differences in children’s reading attitudes at the beginning of the programme and half way through the programme. The study was carried out in three representative clubs. This paper evaluates the attitudes of 65 children towards the clubs and the activities conducted at the clubs. It outlines the children’s beliefs about reading and the extent to which they value reading. It further explores how much KidsREAD clubs have influenced their attitudes towards reading in general and their enjoyment of reading in particular.

A multi-model evaluation of aerosols over South Asia: common problems and possible causes

Atmospheric pollution over South Asia attracts special attention due to its effects on regional climate, water cycle and human health. These effects are potentially growing owing to rising trends of anthropogenic aerosol emissions. In this study, the spatio-temporal aerosol distributions over South Asia from seven global aerosol models are evaluated against aerosol retrievals from NASA satellite sensors and ground-based measurements for the period of 2000–2007. Overall, substantial underestimations of aerosol loading over South Asia are found systematically in most model simulations. Averaged over the entire South Asia, the annual mean aerosol optical depth (AOD) is underestimated by a range 15 to 44% across models compared to MISR (Multi-angle Imaging SpectroRadiometer), which is the lowest bound among various satellite AOD retrievals (from MISR, SeaWiFS (Sea-Viewing Wide Field-of-View Sensor), MODIS (Moderate Resolution Imaging Spectroradiometer) Aqua and Terra). In particular during the post-monsoon and wintertime periods (i.e., October–January), when agricultural waste burning and anthropogenic emissions dominate, models fail to capture AOD and aerosol absorption optical depth (AAOD) over the Indo–Gangetic Plain (IGP) compared to ground-based Aerosol Robotic Network (AERONET) sunphotometer measurements. The underestimations of aerosol loading in models generally occur in the lower troposphere (below 2 km) based on the comparisons of aerosol extinction profiles calculated by the models with those from Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) data. Furthermore, surface concentrations of all aerosol components (sulfate, nitrate, organic aerosol (OA) and black carbon (BC)) from the models are found much lower than in situ measurements in winter. Several possible causes for these common problems of underestimating aerosols in models during the post-monsoon and wintertime periods are identified: the aerosol hygroscopic growth and formation of secondary inorganic aerosol are suppressed in the models because relative humidity (RH) is biased far too low in the boundary layer and thus foggy conditions are poorly represented in current models, the nitrate aerosol is either missing or inadequately accounted for, and emissions from agricultural waste burning and biofuel usage are too low in the emission inventories. These common problems and possible causes found in multiple models point out directions for future model improvements in this important region.

Evaluation of positioning error-induced pixel shifts on satellite linear push-broom imagery

Georeferencing is one of the major tasks of satellite-borne remote sensing. Compared to traditional indirect methods, direct georeferencing through a Global Positioning System/inertial navigation system requires fewer and simpler steps to obtain exterior orientation parameters of remotely sensed images. However, the pixel shift caused by geographic positioning error, which is generally derived from boresight angle as well as terrain topography variation, can have a great impact on the precision of georeferencing. The distribution of pixel shifts introduced by the positioning error on a satellite linear push-broom image is quantitatively analyzed. We use the variation of the object space coordinate to simulate different kinds of positioning errors and terrain topography. Then a total differential method was applied to establish a rigorous sensor model in order to mathematically obtain the relationship between pixel shift and positioning error. Finally, two simulation experiments are conducted using the imaging parameters of Chang’ E-1 satellite to evaluate two different kinds of positioning errors. The experimental results have shown that with the experimental parameters, the maximum pixel shift could reach 1.74 pixels. The proposed approach can be extended to a generic application for imaging error modeling in remote sensing with terrain variation.

Decadal predictions with the HiGEM high resolution global coupled climate model: description and basic evaluation

This paper describes the development and basic evaluation of decadal predictions produced using the HiGEM coupled climate model. HiGEM is a higher resolution version of the HadGEM1 Met Office Unified Model. The horizontal resolution in HiGEM has been increased to 1.25◦ × 0.83◦ in longitude and latitude for the atmosphere, and 1/3◦ × 1/3◦ globally for the ocean. The HiGEM decadal predictions are initialised using an anomaly assimilation scheme that relaxes anomalies of ocean temperature and salinity to observed anomalies. 10 year hindcasts are produced for 10 start dates (1960, 1965,..., 2000, 2005). To determine the relative contributions to prediction skill from initial conditions and external forcing, the HiGEM decadal predictions are compared to uninitialised HiGEM transient experiments. The HiGEM decadal predictions have substantial skill for predictions of annual mean surface air temperature and 100 m upper ocean temperature. For lead times up to 10 years, anomaly correlations (ACC) over large areas of the North Atlantic Ocean, the Western Pacific Ocean and the Indian Ocean exceed values of 0.6. Initialisation of the HiGEM decadal predictions significantly increases skill over regions of the Atlantic Ocean,the Maritime Continent and regions of the subtropical North and South Pacific Ocean. In particular, HiGEM produces skillful predictions of the North Atlantic subpolar gyre for up to 4 years lead time (with ACC > 0.7), which are significantly larger than the uninitialised HiGEM transient experiments.