Bayesian sample size for exploratory clinical trials incorporating historical data

This paper presents a simple Bayesian approach to sample size determination in clinical trials. It is required that the trial should be large enough to ensure that the data collected will provide convincing evidence either that an experimental treatment is better than a control or that it fails to improve upon control by some clinically relevant difference. The method resembles standard frequentist formulations of the problem, and indeed in certain circumstances involving 'non-informative' prior information it leads to identical answers. In particular, unlike many Bayesian approaches to sample size determination, use is made of an alternative hypothesis that an experimental treatment is better than a control treatment by some specified magnitude. The approach is introduced in the context of testing whether a single stream of binary observations are consistent with a given success rate p(0). Next the case of comparing two independent streams of normally distributed responses is considered, first under the assumption that their common variance is known and then for unknown variance. Finally, the more general situation in which a large sample is to be collected and analysed according to the asymptotic properties of the score statistic is explored. Copyright (C) 2007 John Wiley & Sons, Ltd.

Negotiating access into firms: obstacles and strategies

Researchers often experience difficulties with the negotiation of access into firms for the purpose of data collection. The question we explore is: What are the main obstacles associated with access negotiation into firms; and what strategies do researchers employ to increase their chances of success? Our research work on the tendering process of contractors took place between 2006 and 2008. We successfully negotiated access into four firms (two each in Ghana and the UK) to observe live examples of tender preparation The techniques we employed in negotiating access were personal contacts, contacting firms through online details and professional institutions, etc. With all of this effort, our average success rate was less than 5 per cent. The main obstacles encountered were firms’ reluctance because of commercial sensitiveness and fear that the data could eventually be divulged to their competitors or end up in the public domain. However, some firms agreed mainly because of the written assurances of confidentiality and anonymity in reporting the study; reputation of the researchers’ academic institution; gatekeepers who spoke to their colleagues on our behalf; academic purpose of the study; and a feedback report which was promised in return for access to the case studies. Although the access through personal contacts is by far the easiest, it is not always possible. Researchers can approach firms as complete strangers, especially in a foreign country, and that could make the firms more likely to assist the research.

Rapid protein domain assignment from amino acid sequence using predicted secondary structure

The elucidation of the domain content of a given protein sequence in the absence of determined structure or significant sequence homology to known domains is an important problem in structural biology. Here we address how successfully the delineation of continuous domains can be accomplished in the absence of sequence homology using simple baseline methods, an existing prediction algorithm (Domain Guess by Size), and a newly developed method (DomSSEA). The study was undertaken with a view to measuring the usefulness of these prediction methods in terms of their application to fully automatic domain assignment. Thus, the sensitivity of each domain assignment method was measured by calculating the number of correctly assigned top scoring predictions. We have implemented a new continuous domain identification method using the alignment of predicted secondary structures of target sequences against observed secondary structures of chains with known domain boundaries as assigned by Class Architecture Topology Homology (CATH). Taking top predictions only, the success rate of the method in correctly assigning domain number to the representative chain set is 73.3%. The top prediction for domain number and location of domain boundaries was correct for 24% of the multidomain set (±20 residues). These results have been put into context in relation to the results obtained from the other prediction methods assessed

The REFLEX project: Comparing different algorithms and implementations for the inversion of a terrestrial ecosystem model against eddy covariance data

We describe a model-data fusion (MDF) inter-comparison project (REFLEX), which compared various algorithms for estimating carbon (C) model parameters consistent with both measured carbon fluxes and states and a simple C model. Participants were provided with the model and with both synthetic net ecosystem exchange (NEE) of CO2 and leaf area index (LAI) data, generated from the model with added noise, and observed NEE and LAI data from two eddy covariance sites. Participants endeavoured to estimate model parameters and states consistent with the model for all cases over the two years for which data were provided, and generate predictions for one additional year without observations. Nine participants contributed results using Metropolis algorithms, Kalman filters and a genetic algorithm. For the synthetic data case, parameter estimates compared well with the true values. The results of the analyses indicated that parameters linked directly to gross primary production (GPP) and ecosystem respiration, such as those related to foliage allocation and turnover, or temperature sensitivity of heterotrophic respiration, were best constrained and characterised. Poorly estimated parameters were those related to the allocation to and turnover of fine root/wood pools. Estimates of confidence intervals varied among algorithms, but several algorithms successfully located the true values of annual fluxes from synthetic experiments within relatively narrow 90% confidence intervals, achieving >80% success rate and mean NEE confidence intervals <110 gC m−2 year−1 for the synthetic case. Annual C flux estimates generated by participants generally agreed with gap-filling approaches using half-hourly data. The estimation of ecosystem respiration and GPP through MDF agreed well with outputs from partitioning studies using half-hourly data. Confidence limits on annual NEE increased by an average of 88% in the prediction year compared to the previous year, when data were available. Confidence intervals on annual NEE increased by 30% when observed data were used instead of synthetic data, reflecting and quantifying the addition of model error. Finally, our analyses indicated that incorporating additional constraints, using data on C pools (wood, soil and fine roots) would help to reduce uncertainties for model parameters poorly served by eddy covariance data.

The mechanical properties of amniotic membrane influence its effect as a biomaterial for ocular surface repair

The human amniotic membrane (AM) is a tissue of fetal origin and has proven to be clinically useful as a biomaterial in the management of various ocular surface disorders including corneal stem cell transplantation. However, its success rate displays a degree of clinical unpredictability. We suggest that the measured variability inAMstiffness offers an explanation for the poor clinical reproducibility when it is used as a substrate for stem cell expansion and transplantation. Corneal epithelial stem cells were expanded upon AM samples possessing different mechanical stiffness. To investigate further the importance of biological substrate stiffness on cell phenotype we replaced AM with type I collagen gels of known stiffness. Substrate stiffness was measured using shear rheometry and surface topography was characterized using scanning electron microscopy and atomic force microscopy. The differentiation status of epithelial cells was examined using RT-PCR, immunohistochemistry and Western blotting. The level of corneal stem cell differentiation was increased in cells expanded upon AM with a high dynamic elastic shear modulus and cell expansion on type I collagen gels confirmed that the level of corneal epithelial stem cell differentiation was related to the substrate’s mechanical properties. In this paper we provide evidence to show that the preparatory method of AM for clinical use can affect its mechanical properties and that these measured differences can influence the level of differentiation within expanded corneal epithelial stem cells.

Refereed journal papers: practice and process

Research must be published, otherwise it will be lost. The most important papers for a researcher to produce are those published in international refereed journals. Good practice in writing papers is something that can be learned. The editorial process involves sending submitted papers to independent experts in the field, usually anonymously, and their comments inform the editor, who decides whether and how to progress with a paper. Much of this is as obscure to experienced researchers as it is to new ones. With forethought and planning, the success rate of getting submitted papers accepted for publication can be increased. Editors and publishers are generally very keen to help people improve their success rate.

Assessment of the CMD Mini-Explorer, a new low-frequency multi-coil electromagnetic device, for archaeological investigations

In this article we assess the abilities of a new electromagnetic (EM) system, the CMD Mini-Explorer, for prospecting of archaeological features in Ireland and the UK. The Mini-Explorer is an EM probe which is primarily aimed at the environmental/geological prospecting market for the detection of pipes and geology. It has long been evident from the use of other EM devices that such an instrument might be suitable for shallow soil studies and applicable for archaeological prospecting. Of particular interest for the archaeological surveyor is the fact that the Mini-Explorer simultaneously obtains both quadrature (‘conductivity’) and in-phase (relative to ‘magnetic susceptibility’) data from three depth levels. As the maximum depth range is probably about 1.5 m, a comprehensive analysis of the subsoil within that range is possible. As with all EM devices the measurements require no contact with the ground, thereby negating the problem of high contact resistance that often besets earth resistance data during dry spells. The use of the CMD Mini-Explorer at a number of sites has demonstrated that it has the potential to detect a range of archaeological features and produces high-quality data that are comparable in quality to those obtained from standard earth resistance and magnetometer techniques. In theory the ability to measure two phenomena at three depths suggests that this type of instrument could reduce the number of poor outcomes that are the result of single measurement surveys. The high success rate reported here in the identification of buried archaeology using a multi-depth device that responds to the two most commonly mapped geophysical phenomena has implications for evaluation style surveys. Copyright © 2013 John Wiley & Sons, Ltd.

Long-term storage of ectomycorrhizal basidiomycetes (Hebeloma spp.) at low temperature

A method for maintaining viable cultures of ectomycorrhizal Hebeloma strains in cold liquid culture medium is described. Isolates of Hebeloma spp., collected over a wide geographic range, were stored at 2 °C for a period of three years. All cultures survived this storage period, a greater time period and success rate than has previously been reported for the long term storage of ectomycorrhizal basidiomycetes. The method may prove useful for long-term storage of other basidiomycete genera.

Intrafirm causal ambiguity in an international context

This paper examined the incidence of intrafirmcausalambiguity in the management's perception concerning the critical drivers of their firms’ performance. Building on insights from the resource-based view we developed and tested hypotheses that examine (1) linkage ambiguity as a discrepancy between perceived and measured resource–performance linkages, (2) characteristic ambiguity for resources and capabilities with a high degree of complexity and tacitness, and (3) the negative association between linkage ambiguity and performance. The observations based on the explicit perceptions of 356 surveyed managers were contrasted with the empirical findings of the resource/performance relationship derived by structural equation modelling from the same data sample. The findings validate the presence of linkage ambiguity particularly in the case of resources and capabilities with higher degree of characteristic ambiguity. The findings also provide empirical evidence in support of the advocacy for a negative relationship between intrafirmcausalambiguity and performance. The paper discusses the potential reasons for the disparities between empirical findings and management's perceptions of the key determinants of export success and makes recommendations for future research.

Agriculture modifies the seasonal decline of breeding success in a tropical wild bird population

1.Habitat conversion for agriculture is a major driver of biodiversity loss, but our understanding of the demographic processes involved remains poor. We typically investigate the impacts of agriculture in isolation even though populations are likely to experience multiple, concurrent changes in the environment (e.g. land and climate change). Drivers of environmental change may interact to affect demography but the mechanisms have yet to be explored fully in wild populations. 2.Here, we investigate the mechanisms linking agricultural land-use with breeding success using long-term data for the formerly Critically Endangered Mauritius kestrel Falco punctatus; a tropical forest specialist that also occupies agricultural habitats. We specifically focused on the relationship between breeding success, agriculture and the timing of breeding because the latter is sensitive to changes in climatic conditions (spring rainfall), and enables us to explore the interactive effects of different (land and climate) drivers of environmental change. 3.Breeding success, measured as egg survival to fledging, declines seasonally in this population, but we found that the rate of this decline became increasingly rapid as the area of agriculture around a nest site increased. If the relationship between breeding success and agriculture was used in isolation to estimate the demographic impact of agriculture it would significantly under-estimate breeding success in dry (early) springs, and over-estimate breeding success in wet (late) springs. 4.Analysis of prey delivered to nests suggests that the relationship between breeding success and agriculture might be due, in part, to spatial variation in the availability of native, arboreal geckos. 5.Synthesis and applications. Agriculture modifies the seasonal decline in breeding success in this population. As springs are becoming wetter in our study area and since the kestrels breed later in wetter springs, the impact of agriculture on breeding success will become worse over time. Our results suggest that forest restoration designed to reduce the detrimental impacts of agriculture on breeding may also help reduce the detrimental effects of breeding late due to wetter springs. Our results therefore highlight the importance of considering the interactive effects of environmental change when managing wild populations.

Are ericoid mycorrhizas a factor in the success of Calluna vulgaris Heathland Restoration?

Methods used in the restoration of lowland heath vary depending on edaphic factors at a site and need for introduction of ericaceous propagules. This study investigates the effect of some methods on growth of an important ericaceous species, Heather (Calluna vulgaris). It also explores whether success of growth of C. vulgaris in restoration schemes is affected by its degree of colonization by ericoid mycorrhizal fungi (ERM). The success of Heather growth was compared at three sites, a control area of natural heathland and two restoration sites. These were a quarry where soil had been translocated but not chemically manipulated and a site on agricultural land where the top soil had been improved but then either stripped away or acidified prior to attempting heathland restoration. Propagules of C. vulgaris were applied either as turves or as clippings. Results show that clippings produced as dense a cover of C. vulgaris as turves over a period of 13 years and that plants in such swards can exhibit a degree of ERM colonization comparable to that found in mature plants growing in natural heathland. Young (<2 years of age) plants of C. vulgaris had less extensive mycorrhizal colonization of their roots, particularly when growing on restored agricultural soils. A relationship was found between lower levels of mycorrhizal colonization and smaller aboveground plant growth. Success of heathland restoration may be improved by finding means to enhance the rate and extent of mycorrhizal colonization of young C. vulgaris growing in a restoration environment.