Do children with Williams syndrome really have good vocabulary knowledge? Methods for comparing cognitive and linguistic abilities in developmental disorders

The comparison of cognitive and linguistic skills in individuals with developmental disorders is fraught with methodological and psychometric difficulties. In this paper, we illustrate some of these issues by comparing the receptive vocabulary knowledge and non-verbal reasoning abilities of 41 children with Williams syndrome, a genetic disorder in which language abilities are often claimed to be relatively strong. Data from this group were compared with data from typically developing children, children with Down syndrome, and children with non-specific learning difficulties using a number of approaches including comparison of age-equivalent scores, matching, analysis of covariance, and regression-based standardization. Across these analyses children with Williams syndrome consistently demonstrated relatively good receptive vocabulary knowledge, although this effect appeared strongest in the oldest children.

Methods for comparing and constraining models of dendritic spines

Physiological evidence using Infrared Video Microscopy during the uncaging of glutamate has proven the existence of excitable calcium ion channels in spine heads, highlighting the need for reliable models of spines. In this study we compare the three main methods of simulating excitable spines: Baer & Rinzel's Continuum (B&R) model, Coombes' Spike-Diffuse-Spike (SDS) model and paired cable and ion channel equations (Cable model). Tests are done to determine how well the models approximate each other in terms of speed and heights of travelling waves. Significant quantitative differences are found between the models: travelling waves in the SDS model in particular are found to travel at much lower speeds and sometimes much higher voltages than in the Cable or B&R models. Meanwhile qualitative differences are found between the B&R and SDS models over realistic parameter ranges. The cause of these differences is investigated and potential solutions proposed.

Synapsing variable length crossover: An algorithm for crossing and comparing variable length genomes

The Synapsing Variable Length Crossover (SVLC) algorithm provides a biologically inspired method for performing meaningful crossover between variable length genomes. In addition to providing a rationale for variable length crossover it also provides a genotypic similarity metric for variable length genomes enabling standard niche formation techniques to be used with variable length genomes. Unlike other variable length crossover techniques which consider genomes to be rigid inflexible arrays and where some or all of the crossover points are randomly selected, the SVLC algorithm considers genomes to be flexible and chooses non-random crossover points based on the common parental sequence similarity. The SVLC Algorithm recurrently "glues" or synapses homogenous genetic sub-sequences together. This is done in such a way that common parental sequences are automatically preserved in the offspring with only the genetic differences being exchanged or removed, independent of the length of such differences. In a variable length test problem the SVLC algorithm is shown to outperform current variable length crossover techniques. The SVLC algorithm is also shown to work in a more realistic robot neural network controller evolution application.

A framework for comparing pollinator performance: effectiveness and efficiency

Measuring pollinator performance has become increasingly important with emerging needs for risk assessment in conservation and sustainable agriculture that require multi-year and multi-site comparisons across studies. However, comparing pollinator performance across studies is difficult because of the diversity of concepts and disparate methods in use. Our review of the literature shows many unresolved ambiguities. Two different assessment concepts predominate: the first estimates stigmatic pollen deposition and the underlying pollinator behaviour parameters, while the second estimates the pollinator’s contribution to plant reproductive success, for example in terms of seed set. Both concepts include a number of parameters combined in diverse ways and named under a diversity of synonyms and homonyms. However, these concepts are overlapping because pollen deposition success is the most frequently used proxy for assessing the pollinator’s contribution to plant reproductive success. We analyse the diverse concepts and methods in the context of a new proposed conceptual framework with a modular approach based on pollen deposition, visit frequency, and contribution to seed set relative to the plant’s maximum female reproductive potential. A system of equations is proposed to optimize the balance between idealised theoretical concepts and practical operational methods. Our framework permits comparisons over a range of floral phenotypes, and spatial and temporal scales, because scaling up is based on the same fundamental unit of analysis, the single visit.

Comparing tube models for predicting the linear rheology of branched polymer melts

The hierarchical and "bob" (or branch-on-branch) models are tube-based computational models recently developed for predicting the linear rheology of general mixtures of polydisperse branched polymers. These two models are based on a similar tube-theory framework but differ in their numerical implementation and details of relaxation mechanisms. We present a detailed overview of the similarities and differences of these models and examine the effects of these differences on the predictions of the linear viscoelastic properties of a set of representative branched polymer samples in order to give a general picture of the performance of these models. Our analysis confirms that the hierarchical and bob models quantitatively predict the linear rheology of a wide range of branched polymer melts but also indicate that there is still no unique solution to cover all types of branched polymers without case-by-case adjustment of parameters such as the dilution exponent alpha and the factor p(2) which defines the hopping distance of a branch point relative to the tube diameter. An updated version of the hierarchical model, which shows improved computational efficiency and refined relaxation mechanisms, is introduced and used in these analyses.

Comparing a discrete and continuum model of the intestinal crypt

The integration of processes at different scales is a key problem in the modelling of cell populations. Owing to increased computational resources and the accumulation of data at the cellular and subcellular scales, the use of discrete, cell-level models, which are typically solved using numerical simulations, has become prominent. One of the merits of this approach is that important biological factors, such as cell heterogeneity and noise, can be easily incorporated. However, it can be difficult to efficiently draw generalizations from the simulation results, as, often, many simulation runs are required to investigate model behaviour in typically large parameter spaces. In some cases, discrete cell-level models can be coarse-grained, yielding continuum models whose analysis can lead to the development of insight into the underlying simulations. In this paper we apply such an approach to the case of a discrete model of cell dynamics in the intestinal crypt. An analysis of the resulting continuum model demonstrates that there is a limited region of parameter space within which steady-state (and hence biologically realistic) solutions exist. Continuum model predictions show good agreement with corresponding results from the underlying simulations and experimental data taken from murine intestinal crypts.

An ECOOP web portal for visualising and comparing distributed coastal oceanography model and in situ data

As part of a large European coastal operational oceanography project (ECOOP), we have developed a web portal for the display and comparison of model and in situ marine data. The distributed model and in situ datasets are accessed via an Open Geospatial Consortium Web Map Service (WMS) and Web Feature Service (WFS) respectively. These services were developed independently and readily integrated for the purposes of the ECOOP project, illustrating the ease of interoperability resulting from adherence to international standards. The key feature of the portal is the ability to display co-plotted timeseries of the in situ and model data and the quantification of misfits between the two. By using standards-based web technology we allow the user to quickly and easily explore over twenty model data feeds and compare these with dozens of in situ data feeds without being concerned with the low level details of differing file formats or the physical location of the data. Scientific and operational benefits to this work include model validation, quality control of observations, data assimilation and decision support in near real time. In these areas it is essential to be able to bring different data streams together from often disparate locations.

PINCER trial: a cluster randomised trial comparing the effectiveness and cost-effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Background: Medication errors in general practice are an important source of potentially preventable morbidity and mortality. Building on previous descriptive, qualitative and pilot work, we sought to investigate the effectiveness, cost-effectiveness and likely generalisability of a complex pharm acist-led IT-based intervention aiming to improve prescribing safety in general practice. Objectives: We sought to: • Test the hypothesis that a pharmacist-led IT-based complex intervention using educational outreach and practical support is more effective than simple feedback in reducing the proportion of patients at risk from errors in prescribing and medicines management in general practice. • Conduct an economic evaluation of the cost per error avoided, from the perspective of the National Health Service (NHS). • Analyse data recorded by pharmacists, summarising the proportions of patients judged to be at clinical risk, the actions recommended by pharmacists, and actions completed in the practices. • Explore the views and experiences of healthcare professionals and NHS managers concerning the intervention; investigate potential explanations for the observed effects, and inform decisions on the future roll-out of the pharmacist-led intervention • Examine secular trends in the outcome measures of interest allowing for informal comparison between trial practices and practices that did not participate in the trial contributing to the QRESEARCH database. Methods Two-arm cluster randomised controlled trial of 72 English general practices with embedded economic analysis and longitudinal descriptive and qualitative analysis. Informal comparison of the trial findings with a national descriptive study investigating secular trends undertaken using data from practices contributing to the QRESEARCH database. The main outcomes of interest were prescribing errors and medication monitoring errors at six- and 12-months following the intervention. Results: Participants in the pharmacist intervention arm practices were significantly less likely to have been prescribed a non-selective NSAID without a proton pump inhibitor (PPI) if they had a history of peptic ulcer (OR 0.58, 95%CI 0.38, 0.89), to have been prescribed a beta-blocker if they had asthma (OR 0.73, 95% CI 0.58, 0.91) or (in those aged 75 years and older) to have been prescribed an ACE inhibitor or diuretic without a measurement of urea and electrolytes in the last 15 months (OR 0.51, 95% CI 0.34, 0.78). The economic analysis suggests that the PINCER pharmacist intervention has 95% probability of being cost effective if the decision-maker’s ceiling willingness to pay reaches £75 (6 months) or £85 (12 months) per error avoided. The intervention addressed an issue that was important to professionals and their teams and was delivered in a way that was acceptable to practices with minimum disruption of normal work processes. Comparison of the trial findings with changes seen in QRESEARCH practices indicated that any reductions achieved in the simple feedback arm were likely, in the main, to have been related to secular trends rather than the intervention. Conclusions Compared with simple feedback, the pharmacist-led intervention resulted in reductions in proportions of patients at risk of prescribing and monitoring errors for the primary outcome measures and the composite secondary outcome measures at six-months and (with the exception of the NSAID/peptic ulcer outcome measure) 12-months post-intervention. The intervention is acceptable to pharmacists and practices, and is likely to be seen as costeffective by decision makers.

Comparing the UK Met Office climate prediction system DePreSys with idealized predictability in the HadCM3 model

The initial condition effect on climate prediction skill over a 2-year hindcast time-scale has been assessed from ensemble HadCM3 climate model runs using anomaly initialization over the period 1990–2001, and making comparisons with runs without initialization (equivalent to climatological conditions), and to anomaly persistence. It is shown that the assimilation improves the prediction skill in the first year globally, and in a number of limited areas out into the second year. Skill in hindcasting surface air temperature anomalies is most marked over ocean areas, and is coincident with areas of high sea surface temperature and ocean heat content skill. Skill improvement over land areas is much more limited but is still detectable in some cases. We found little difference in the skill of hindcasts using three different sets of ocean initial conditions, and we obtained the best results by combining these to form a grand ensemble hindcast set. Results are also compared with the idealized predictability studies of Collins (Clim. Dynam. 2002; 19: 671–692), which used the same model. The maximum lead time for which initialization gives enhanced skill over runs without initialization varies in different regions but is very similar to lead times found in the idealized studies, therefore strongly supporting the process representation in the model as well as its use for operational predictions. The limited 12-year period of the study, however, means that the regional details of model skill should probably be further assessed under a wider range of observational conditions.