Investigating the prevalence and causes of prescribing errors in general practice: the PRACtICe Study

Aim: To determine the prevalence and nature of prescribing errors in general practice; to explore the causes, and to identify defences against error. Methods: 1) Systematic reviews; 2) Retrospective review of unique medication items prescribed over a 12 month period to a 2% sample of patients from 15 general practices in England; 3) Interviews with 34 prescribers regarding 70 potential errors; 15 root cause analyses, and six focus groups involving 46 primary health care team members Results: The study involved examination of 6,048 unique prescription items for 1,777 patients. Prescribing or monitoring errors were detected for one in eight patients, involving around one in 20 of all prescription items. The vast majority of the errors were of mild to moderate severity, with one in 550 items being associated with a severe error. The following factors were associated with increased risk of prescribing or monitoring errors: male gender, age less than 15 years or greater than 64 years, number of unique medication items prescribed, and being prescribed preparations in the following therapeutic areas: cardiovascular, infections, malignant disease and immunosuppression, musculoskeletal, eye, ENT and skin. Prescribing or monitoring errors were not associated with the grade of GP or whether prescriptions were issued as acute or repeat items. A wide range of underlying causes of error were identified relating to the prescriber, patient, the team, the working environment, the task, the computer system and the primary/secondary care interface. Many defences against error were also identified, including strategies employed by individual prescribers and primary care teams, and making best use of health information technology. Conclusion: Prescribing errors in general practices are common, although severe errors are unusual. Many factors increase the risk of error. Strategies for reducing the prevalence of error should focus on GP training, continuing professional development for GPs, clinical governance, effective use of clinical computer systems, and improving safety systems within general practices and at the interface with secondary care.

Relaxing the Tropics to an ‘observed’ state: analysis using a simple baroclinic model

The technique of relaxation of the tropical atmosphere towards an analysis in a month-season forecast model has previously been successfully exploited in a number of contexts. Here it is shown that when tropical relaxation is used to investigate the possible origin of the observed anomalies in June–July 2007, a simple dynamical model is able to reproduce the observed component of the pattern of anomalies given by an ensemble of ECMWF forecast runs. Following this result, the simple model is used for a range of experiments on time-scales of relaxation, variables and regions relaxed based on a control model run with equatorial heating in a zonal flow. A theory based on scale analysis for the large-scale tropics is used to interpret the results. Typical relationships between scales are determined from the basic equations, and for a specified diabatic heating a chain of deductions for determining the dependent variables is derived. Different critical time-scales are found for tropical relaxation of different dependent variables to be effective. Vorticity has the longest critical time-scale, typically 1.2 days. For temperature and divergence, the time-scales are 10 hours and 3 hours, respectively. However not all the tropical fields, in particular the vertical motion, are reproduced correctly by the model unless divergence is heavily damped. To obtain the correct extra-tropical fields, it is crucial to have the correct rotational flow in the subtropics to initiate the Rossby wave propagation from there. It is sufficient to relax vorticity or temperature on a time-scale comparable or less than their critical time-scales to obtain this. However if the divergent advection of vorticity is important in the Rossby Wave Source then strong relaxation of divergence is required to accurately represent the tropical forcing of Rossby waves.

Synthesis and incorporation into cyclic peptides of tolan amino acids and their hydrogenated congeners: construction of an array of A–B-loop mimetics of the Cε3 domain of human IgE

The disruption of the human immunolobulin E–high affinity receptor I (IgE–FcεRI) protein–protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A–B loop within the Cε3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC50 660 μM) is displayed by the peptide containing a 2,2′-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A–B loop epitope in IgE.

A nipple shield delivery system for oral drug delivery to breastfeeding infants : Microbicide delivery to inactivate HIV

A new drug delivery method for infants is presented which incorporates an active pharmaceutical ingredient (API)-loaded insert into a nipple shield delivery system (NSDS). The API is released directly into milk during breastfeeding. This study investigates the feasibility of using the NSDS to deliver the microbicide sodium dodecyl sulfate (SDS), with the goal of preventing mother-to-child transmission (MTCT) of HIV during breastfeeding in low-resource settings, when there is no safer alternative for the infant but to breastfeed. SDS has been previously shown to effectively inactivate HIV in human milk. An apparatus was developed to simulate milk flow through and drug release from a NSDS. Using this apparatus milk was pulsed through a prototype device containing a non-woven fiber insert impregnated with SDS and the microbicide was rapidly released. The total SDS release from inserts ranged from 70 to 100% of the average 0.07 g load within 50 ml (the volume of a typical breastfeed). Human milk spiked with H9/HIVIIIB cells was also passed through the same set-up. Greater than 99% reduction of cell-associated HIV infectivity was achieved in the first 10 ml of milk. This proof of concept study demonstrates efficient drug delivery to breastfeeding infants is achievable using the NSDS.

Operator space structure of JC*-triples and TROs, I

We embark upon a systematic investigation of operator space structure of JC*-triples via a study of the TROs (ternary rings of operators) they generate. Our approach is to introduce and develop a variety of universal objects, including universal TROs, by which means we are able to describe all possible operator space structures of a JC*-triple. Via the concept of reversibility we obtain characterisations of universal TROs over a wide range of examples. We apply our results to obtain explicit descriptions of operator space structures of Cartan factors regardless of dimension

Context and aims of the Aqua-Planet Experiment

The Aqua-Planet Experiment (APE) was first proposed by Neale and Hoskins (2000a) as a benchmark for atmospheric general circulation models (AGCMs) on an idealised water-covered Earth. The experiment and its aims are summarised, and its context within a modelling hierarchy used to evaluate complex models and to provide a link between realistic simulation and conceptual models of atmospheric phenomena is discussed. The simplified aqua-planet configuration bridges a gap in the existing hierarchy. It is designed to expose differences between models and to focus attention on particular phenomena and their response to changes in the underlying distribution of sea surface temperature.

The influence of the QBO on the propagation of equatorial waves into the stratosphere

The variation of stratospheric equatorial wave characteristics with the phase of the quasi-biennial oscillation (QBO) is investigated using ECMWF Re-Analysis and NOAA outgoing longwave radiation (OLR) data. The impact of the QBO phases on the upward propagation of equatorial waves is found to be consistent and significant. In the easterly phase, there is larger Kelvin wave amplitude but smaller westward-moving mixed Rossby–gravity (WMRG) and n = 1 Rossby (R1) wave amplitude due to reduced propagation from the upper troposphere into the lower stratosphere, compared with the westerly phase. Differences in the wave amplitude exist in a deeper layer in summer than in winter, consistent with the seasonality of ambient zonal winds. There is a strong evidence of Kelvin wave amplitude peaking just below the descending westerly phase, suggesting that Kelvin waves act to bring the westerly phase downward. However, the corresponding evidence for WMRG and R1 waves is less clear. In the lower stratosphere there is zonal variation in equatorial waves. This reflects the zonal asymmetry of wave amplitudes in the upper troposphere, the source for the lower-stratospheric waves. In easterly winters the upper-tropospheric WMRG and R1 waves over the eastern Pacific region appear to be somewhat stronger compared to climatology, perhaps because of the accumulation of waves that are unable to propagate upward into the lower stratosphere. Vertical propagation features of these waves are generally consistent with theory and suggest a mixture of Doppler shifting by ambient flows and filtering. Some lower-stratosphere equatorial waves have a connection with preceding tropical convection, especially for Kelvin and R1 waves in winter.

A unifying framework for metrics for aggregating the climate effect of different emissions

Multi-gas approaches to climate change policies require a metric establishing ‘equivalences’ among emissions of various species. Climate scientists and economists have proposed four kinds of such metrics and debated their relative merits. We present a unifying framework that clarifies the relationships among them. We show, as have previous authors, that the global warming potential (GWP), used in international law to compare emissions of greenhouse gases, is a special case of the global damage potential (GDP), assuming (1) a finite time horizon, (2) a zero discount rate, (3) constant atmospheric concentrations, and (4) impacts that are proportional to radiative forcing. Both the GWP and GDP follow naturally from a cost–benefit framing of the climate change issue. We show that the global temperature change potential (GTP) is a special case of the global cost potential (GCP), assuming a (slight) fall in the global temperature after the target is reached. We show how the four metrics should be generalized if there are intertemporal spillovers in abatement costs, distinguishing between private (e.g., capital stock turnover) and public (e.g., induced technological change) spillovers. Both the GTP and GCP follow naturally from a cost-effectiveness framing of the climate change issue. We also argue that if (1) damages are zero below a threshold and (2) infinitely large above a threshold, then cost-effectiveness analysis and cost–benefit analysis lead to identical results. Therefore, the GCP is a special case of the GDP. The UN Framework Convention on Climate Change uses the GWP, a simplified cost–benefit concept. The UNFCCC is framed around the ultimate goal of stabilizing greenhouse gas concentrations. Once a stabilization target has been agreed under the convention, implementation is clearly a cost-effectiveness problem. It would therefore be more consistent to use the GCP or its simplification, the GTP.

The monitoring of ecological quality and the classification of standing waters in temperate regions: a review and proposal based on a worked scheme for British waters

This paper reviews the ways that quality can be assessed in standing waters, a subject that has hitherto attracted little attention but which is now a legal requirement in Europe. It describes a scheme for the assessment and monitoring of water and ecological quality in standing waters greater than about I ha in area in England & Wales although it is generally relevant to North-west Europe. Thirteen hydrological, chemical and biological variables are used to characterise the standing water body in any current sampling. These are lake volume, maximum depth, onductivity, Secchi disc transparency, pH, total alkalinity, calcium ion concentration, total N concentration,winter total oxidised inorganic nitrogen (effectively nitrate) concentration, total P concentration, potential maximum chlorophyll a concentration, a score based on the nature of the submerged and emergent plant community, and the presence or absence of a fish community. Inter alia these variables are key indicators of the state of eutrophication, acidification, salinisation and infilling of a water body.

The determination of total nitrogen and total phosphorus concentrations in freshwaters from land use, stock headage and population data: testing of a model for use in conservation and water quality management

1. Nutrient concentrations (particularly N and P) determine the extent to which water bodies are or may become eutrophic. Direct determination of nutrient content on a wide scale is labour intensive but the main sources of N and P are well known. This paper describes and tests an export coefficient model for prediction of total N and total P from: (i) land use, stock headage and human population; (ii) the export rates of N and P from these sources; and (iii) the river discharge. Such a model might be used to forecast the effects of changes in land use in the future and to hindcast past water quality to establish comparative or baseline states for the monitoring of change. 2. The model has been calibrated against observed data for 1988 and validated against sets of observed data for a sequence of earlier years in ten British catchments varying from uplands through rolling, fertile lowlands to the flat topography of East Anglia. 3. The model predicted total N and total P concentrations with high precision (95% of the variance in observed data explained). It has been used in two forms: the first on a specific catchment basis; the second for a larger natural region which contains the catchment with the assumption that all catchments within that region will be similar. Both models gave similar results with little loss of precision in the latter case. This implies that it will be possible to describe the overall pattern of nutrient export in the UK with only a fraction of the effort needed to carry out the calculations for each individual water body. 4. Comparison between land use, stock headage, population numbers and nutrient export for the ten catchments in the pre-war year of 1931, and for 1970 and 1988 show that there has been a substantial loss of rough grazing to fertilized temporary and permanent grasslands, an increase in the hectarage devoted to arable, consistent increases in the stocking of cattle and sheep and a marked movement of humans to these rural catchments. 5. All of these trends have increased the flows of nutrients with more than a doubling of both total N and total P loads during the period. On average in these rural catchments, stock wastes have been the greatest contributors to both N and P exports, with cultivation the next most important source of N and people of P. Ratios of N to P were high in 1931 and remain little changed so that, in these catchments, phosphorus continues to be the nutrient most likely to control algal crops in standing waters supplied by the rivers studied.

August Thienemann and Loch Lomond - an approach to the design of a system for monitoring the state of north-temperate standing waters

Limnologists had an early preoccupation with lake classification. It gave a necessary structure to the many chemical and biological observations that were beginning to form the basis of one of the earliest truly environmental sciences. August Thienemann was the doyen of such classifiers and his concept with Einar Naumann of oligotrophic and eutrophic lakes remains central to the world-view that limnologists still have. Classification fell into disrepute, however, as it became clear that there would always be lakes that deviated from the prescriptions that the classifiers made for them. Continua became the de rigeur concept and lakes were seen as varying along many chemical, biological and geographic axes. Modern limnologists are comfortable with this concept. That all lakes are different guarantees an indefinite future for limnological research. For those who manage lakes and the landscapes in which they are set, however, it is not very useful. There may be as many as 300000 standing water bodies in England and Wales alone and maybe as many again in Scotland. More than 80 000 are sizable (> 1 ha). Some classification scheme to cope with these numbers is needed and, as human impacts on them increase, a system of assessing and monitoring change must be built into such a scheme. Although ways of classifying and monitoring running waters are well developed in the UK, the same is not true of standing waters. Sufficient understanding of what determines the nature and functioning of lakes exists to create a system which has intellectual credibility as well as practical usefulness. This paper outlines the thinking behind a system which will be workable on a north European basis and presents some early results.

The large-scale circulation change at the end of the Baiu season in Japan as seen in ERA40 data

The time evolution of the circulation change at the end of the Baiu season is investigated using ERA40 data. An end-day is defined for each of the 23 years based on the 850 hPa θe value at 40˚Nin the 130-140˚E sector exceeding 330 K. Daily time series of variables are composited with respect to this day. These composite time-series exhibit a clearer and more rapid change in the precipitation and the large-scale circulation over the whole East Asia region than those performed using calendar days. The precipitation change includes the abrupt end of the Baiu rain, the northward shift of tropical convection perhaps starting a few days before this, and the start of the heavier rain at higher latitudes. The northward migration of lower tropospheric warm, moist tropical air, a general feature of the seasonal march in the region, is fast over the continent and slow over the ocean. By mid to late July the cooler air over the Sea of Japan is surrounded on 3 sides by the tropical air. It is suggestive that the large-scale stage has been set for a jump to the post-Baiu state, i.e., for the end of the Baiu season. Two likely triggers for the actual change emerge from the analysis. The first is the northward movement of tropical convection into the Philippine region. The second is an equivalent barotropic Rossby wave-train, that over a 10-day period develops downstream across Eurasia. It appears likely that in most years one or both mechanisms can be important in triggering the actual end of the Baiu season.

Strategies: Revolution in climate prediction is both necessary and possible: A declaration at the World Modelling Summit for Climate Prediction

The impending threat of global climate change and its regional manifestations is among the most important and urgent problems facing humanity. Society needs accurate and reliable estimates of changes in the probability of regional weather variations to develop science-based adaptation and mitigation strategies. Recent advances in weather prediction and in our understanding and ability to model the climate system suggest that it is both necessary and possible to revolutionize climate prediction to meet these societal needs. However, the scientific workforce and the computational capability required to bring about such a revolution is not available in any single nation. Motivated by the success of internationally funded infrastructure in other areas of science, this paper argues that, because of the complexity of the climate system, and because the regional manifestations of climate change are mainly through changes in the statistics of regional weather variations, the scientific and computational requirements to predict its behavior reliably are so enormous that the nations of the world should create a small number of multinational high-performance computing facilities dedicated to the grand challenges of developing the capabilities to predict climate variability and change on both global and regional scales over the coming decades. Such facilities will play a key role in the development of next-generation climate models, build global capacity in climate research, nurture a highly trained workforce, and engage the global user community, policy-makers, and stakeholders. We recommend the creation of a small number of multinational facilities with computer capability at each facility of about 20 peta-flops in the near term, about 200 petaflops within five years, and 1 exaflop by the end of the next decade. Each facility should have sufficient scientific workforce to develop and maintain the software and data analysis infrastructure. Such facilities will enable questions of what resolution, both horizontal and vertical, in atmospheric and ocean models, is necessary for more confident predictions at the regional and local level. Current limitations in computing power have placed severe limitations on such an investigation, which is now badly needed. These facilities will also provide the world's scientists with the computational laboratories for fundamental research on weather–climate interactions using 1-km resolution models and on atmospheric, terrestrial, cryospheric, and oceanic processes at even finer scales. Each facility should have enabling infrastructure including hardware, software, and data analysis support, and scientific capacity to interact with the national centers and other visitors. This will accelerate our understanding of how the climate system works and how to model it. It will ultimately enable the climate community to provide society with climate predictions, which are based on our best knowledge of science and the most advanced technology.