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Showing papers by "University of Aberdeen published in 2007"


Journal ArticleDOI
19 Jan 2007-Science
TL;DR: It was demonstrated that mind-wandering is associated with activity in a default network of cortical regions that are active when the brain is “at rest” and individuals' reports of the tendency of their minds to wander were correlated with activity on this network.
Abstract: Despite evidence pointing to a ubiquitous tendency of human minds to wander, little is known about the neural operations that support this core component of human cognition. Using both thought sampling and brain imaging, the current investigation demonstrated that mind-wandering is associated with activity in a default network of cortical regions that are active when the brain is "at rest." In addition, individuals' reports of the tendency of their minds to wander were correlated with activity in this network.

2,515 citations


Journal ArticleDOI
TL;DR: There is substantial scope for exploring indirect facilitative effects in plant communities, including their impacts on diversity and evolution, and future studies should connect the degree of non-transitivity in plant competitive networks to community diversity and facilitative promotion of species coexistence.
Abstract: Summary 1 Once neglected, the role of facilitative interactions in plant communities has received considerable attention in the last two decades, and is now widely recognized It is timely to consider the progress made by research in this field 2 We review the development of plant facilitation research, focusing on the history of the field, the relationship between plant‐plant interactions and environmental severity gradients, and attempts to integrate facilitation into mainstream ecological theory We then consider future directions for facilitation research 3 With respect to our fundamental understanding of plant facilitation, clarification of the relationship between interactions and environmental gradients is central for further progress, and necessitates the design and implementation of experiments that move beyond the clear limitations of previous studies 4 There is substantial scope for exploring indirect facilitative effects in plant communities, including their impacts on diversity and evolution, and future studies should connect the degree of non-transitivity in plant competitive networks to community diversity and facilitative promotion of species coexistence, and explore how the role of indirect facilitation varies with environmental severity 5 Certain ecological modelling approaches (eg individual-based modelling), although thus far largely neglected, provide highly useful tools for exploring these fundamental processes 6 Evolutionary responses might result from facilitative interactions, and consideration of facilitation might lead to re-assessment of the evolution of plant growth forms

1,496 citations


Journal ArticleDOI
01 Aug 2007-Methods
TL;DR: The resazurin assay utilising microtitre-plate has been modified to achieve more accuracy in the determination of the minimum inhibitory concentration values of natural products, including crude extracts, chromatographic fractions or purified compounds against various bacterial strains.

1,333 citations


Journal ArticleDOI
Paul Burton1, David Clayton2, Lon R. Cardon1, Nicholas John Craddock3  +221 moreInstitutions (30)
TL;DR: In this paper, the authors report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirm the previously reported association of AITD with TSHR and FCRL3.
Abstract: We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

1,299 citations


Journal ArticleDOI
01 Mar 2007-BMJ
TL;DR: The importance of ground work in getting usable results is explained and the effectiveness of complex interventions can be difficult and time consuming.
Abstract: Determining the effectiveness of complex interventions can be difficult and time consuming. Neil C Campbell and colleagues explain the importance of ground work in getting usable results

1,255 citations


Journal ArticleDOI
TL;DR: It is argued that the full potential of the ongoing revolution in microbial ecology will not be realized if research is not directed and driven by theory, and that the generality of established ecological theory must be tested using microbial systems.
Abstract: Microbial ecology is currently undergoing a revolution, with repercussions spreading throughout microbiology, ecology and ecosystem science. The rapid accumulation of molecular data is uncovering vast diversity, abundant uncultivated microbial groups and novel microbial functions. This accumulation of data requires the application of theory to provide organization, structure, mechanistic insight and, ultimately, predictive power that is of practical value, but the application of theory in microbial ecology is currently very limited. Here we argue that the full potential of the ongoing revolution will not be realized if research is not directed and driven by theory, and that the generality of established ecological theory must be tested using microbial systems.

874 citations


Journal ArticleDOI
TL;DR: The hypothesis that the incidence of acute kidney injury is much higher than previously thought is tested, with implications for service planning and providing information to colleagues about methods to prevent deterioration of renal function.
Abstract: Epidemiological studies of acute kidney injury (AKI) and acute-on-chronic renal failure (ACRF) are surprisingly sparse and confounded by differences in definition. Reported incidences vary, with few studies being population-based. Given this and our aging population, the incidence of AKI may be much higher than currently thought. We tested the hypothesis that the incidence is higher by including all patients with AKI (in a geographical population base of 523,390) regardless of whether they required renal replacement therapy irrespective of the hospital setting in which they were treated. We also tested the hypothesis that the Risk, Injury, Failure, Loss, and End-Stage Kidney (RIFLE) classification predicts outcomes. We identified all patients with serum creatinine concentrations > or =150 micromol/L (male) or > or =130 micromol/L (female) over a 6-mo period in 2003. Clinical outcomes were obtained from each patient's case records. The incidences of AKI and ACRF were 1811 and 336 per million population, respectively. Median age was 76 yr for AKI and 80.5 yr for ACRF. Sepsis was a precipitating factor in 47% of patients. The RIFLE classification was useful for predicting full recovery of renal function (P < 0.001), renal replacement therapy requirement (P < 0.001), length of hospital stay [excluding those who died during admission (P < 0.001)], and in-hospital mortality (P = 0.035). RIFLE did not predict mortality at 90 d or 6 mo. Thus the incidence of AKI is much higher than previously thought, with implications for service planning and providing information to colleagues about methods to prevent deterioration of renal function. The RIFLE classification is useful for identifying patients at greatest risk of adverse short-term outcomes.

785 citations


Journal ArticleDOI
01 Nov 2007-Nature
TL;DR: Functional analyses of two motifs, RXLR and EER, present in translocated oomycete effectors are reported, showing that RXLR-EER-encoding genes are transcriptionally upregulated during infection and 425 potential genes encoding secreted RXLR/EER class proteins in the P. infestans genome are identified.
Abstract: Bacterial, oomycete and fungal plant pathogens establish disease by translocation of effector proteins into host cells, where they may directly manipulate host innate immunity. In bacteria, translocation is through the type III secretion system, but analogous processes for effector delivery are uncharacterized in fungi and oomycetes. Here we report functional analyses of two motifs, RXLR and EER, present in translocated oomycete effectors. We use the Phytophthora infestans RXLR-EER-containing protein Avr3a as a reporter for translocation because it triggers RXLR-EER-independent hypersensitive cell death following recognition within plant cells that contain the R3a resistance protein. We show that Avr3a, with or without RXLR-EER motifs, is secreted from P. infestans biotrophic structures called haustoria, demonstrating that these motifs are not required for targeting to haustoria or for secretion. However, following replacement of Avr3a RXLR-EER motifs with alanine residues, singly or in combination, or with residues KMIK-DDK--representing a change that conserves physicochemical properties of the protein--P. infestans fails to deliver Avr3a or an Avr3a-GUS fusion protein into plant cells, demonstrating that these motifs are required for translocation. We show that RXLR-EER-encoding genes are transcriptionally upregulated during infection. Bioinformatic analysis identifies 425 potential genes encoding secreted RXLR-EER class proteins in the P. infestans genome. Identification of this class of proteins provides unparalleled opportunities to determine how oomycetes manipulate hosts to establish infection.

758 citations


Journal ArticleDOI
TL;DR: In this paper, it is shown by experiment and calculation that much, if not all, of this calcite is reactive and affects the distribution of lime, alumina and sulfate and thereby alters the mineralogy of hydrated cement pastes.

708 citations


Journal ArticleDOI
TL;DR: Investigation of variation in the assimilation and translocation of arsenic in commercially farmed temperate rice, wheat, and barley found that the risk posed by As in the human food-chain needs to be considered in the context of anaerobic verses aerobic ecosystems.
Abstract: Paired grain, shoot, and soil of 173 individual sample sets of commercially farmed temperate rice, wheat, and barley were surveyed to investigate variation in the assimilation and translocation of arsenic (As). Rice samples were obtained from the Carmargue (France), Donana (Spain), Cadiz (Spain), California, and Arkansas. Wheat and barleywere collected from Cornwall and Devon (England) and the east coast of Scotland. Transfer of As from soil to grain was an order of magnitude greater in rice than for wheat and barley, despite lower rates of shoot-to-grain transfer. Rice grain As levels over 0.60 microg g(-1) d. wt were found in rice grown in paddy soil of around only 10 microg g(-1) As, showing that As in paddy soils is problematic with respect to grain As levels. This is due to the high shoot/soil ratio of approximately 0.8 for rice compared to 0.2 and 0.1 for barley and wheat, respectively. The differences in these transfer ratios are probably due to differences in As speciation and dynamics in anaerobic rice soils compared to aerobic soils for barley and wheat. In rice, the export of As from the shoot to the grain appears to be under tight physiological control as the grain/shoot ratio decreases by more than an order of magnitude (from approximately 0.3 to 0.003 mg/kg) and as As levels in the shoots increase from 1 to 20 mg/kg. A down regulation of shoot-to-grain export may occur in wheat and barley, but it was not detected at the shoot As levels found in this survey. Some agricultural soils in southwestern England had levels in excess of 200 microg g(-1) d. wt, although the grain levels for wheat and barley never breached 0.55 microg g(-1) d. wt. These grain levels were achieved in rice in soils with an order of magnitude lower As. Thus the risk posed by As in the human food-chain needs to be considered in the context of anaerobic verses aerobic ecosystems.

665 citations


Journal ArticleDOI
TL;DR: This study aimed to investigate whether the properties of cannabidiol extend to CB1 receptors expressed in mouse brain and to human CB2 receptors that have been transfected into CHO cells.
Abstract: Background and purpose: A nonpsychoactive constituent of the cannabis plant, cannabidiol has been demonstrated to have low affinity for both cannabinoid CB1 and CB2 receptors. We have shown previously that cannabidiol can enhance electrically evoked contractions of the mouse vas deferens, suggestive of inverse agonism. We have also shown that cannabidiol can antagonize cannabinoid receptor agonists in this tissue with a greater potency than we would expect from its poor affinity for cannabinoid receptors. This study aimed to investigate whether these properties of cannabidiol extend to CB1 receptors expressed in mouse brain and to human CB2 receptors that have been transfected into CHO cells.

Journal ArticleDOI
TL;DR: As discussed here, marker-assisted selection and quantitative trait loci cloning for RSA are underway, exploiting genomic resources, candidate genes and the knowledge gained from Arabidopsis, rice and other crops to manipulate root system architecture towards a distribution of roots in the soil that optimizes water and nutrient uptake.

Journal ArticleDOI
TL;DR: In this article, a scheme of phase balances was proposed to calculate the mineralogical balances of a hydrated cement paste with greater accuracy than hitherto practicable, and experimentally-determined phase relationships were depicted at 25 deg. C.


Journal ArticleDOI
05 Dec 2007-Allergy
TL;DR: This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education that are recommended for clinical practice in Europe as well as in North America.
Abstract: Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative, which is endorsed by both academies.

Journal ArticleDOI
TL;DR: Increasing maternal vitamin D intakes during pregnancy may decrease the risk of wheeze symptoms in early childhood, according to a comparison of the highest and lowest quintiles of maternal total vitamin D intake.

Proceedings ArticleDOI
17 Apr 2007
TL;DR: This paper provides a comprehensive review of explanations in recommender systems, highlighting seven possible advantages of an explanation facility, and describing how existing measures can be used to evaluate the quality of explanations.
Abstract: This paper provides a comprehensive review of explanations in recommender systems. We highlight seven possible advantages of an explanation facility, and describe how existing measures can be used to evaluate the quality of explanations. Since explanations are not independent of the recommendation process, we consider how the ways recommendations are presented may affect explanations. Next, we look at different ways of interacting with explanations. The paper is illustrated with examples of explanations throughout, where possible from existing applications.

Journal ArticleDOI
TL;DR: In this article, a database of commonly-encountered cement substances including C-S-H, Ca(OH)2, selected AFm, AFt and hydrogarnet compositions as well as solid solutions is presented.

Journal ArticleDOI
TL;DR: The findings that population screening is unlikely to be cost-effective are based on an economic model whose parameter estimates have considerable uncertainty, which has implications for any future organisational changes in community eye-care services.
Abstract: OBJECTIVES: To assess whether open angle glaucoma (OAG) screening meets the UK National Screening Committee criteria, to compare screening strategies with case finding, to estimate test parameters, to model estimates of cost and cost-effectiveness, and to identify areas for future research. DATA SOURCES: Major electronic databases were searched up to December 2005. REVIEW METHODS: Screening strategies were developed by wide consultation. Markov submodels were developed to represent screening strategies. Parameter estimates were determined by systematic reviews of epidemiology, economic evaluations of screening, and effectiveness (test accuracy, screening and treatment). Tailored highly sensitive electronic searches were undertaken. RESULTS: Most potential screening tests reviewed had an estimated specificity of 85% or higher. No test was clearly most accurate, with only a few, heterogeneous studies for each test. No randomised controlled trials (RCTs) of screening were identified. Based on two treatment RCTs, early treatment reduces the risk of progression. Extrapolating from this, and assuming accelerated progression with advancing disease severity, without treatment the mean time to blindness in at least one eye was approximately 23 years, compared to 35 years with treatment. Prevalence would have to be about 3-4% in 40 year olds with a screening interval of 10 years to approach cost-effectiveness. It is predicted that screening might be cost-effective in a 50-year-old cohort at a prevalence of 4% with a 10-year screening interval. General population screening at any age, thus, appears not to be cost-effective. Selective screening of groups with higher prevalence (family history, black ethnicity) might be worthwhile, although this would only cover 6% of the population. Extension to include other at-risk cohorts (e.g. myopia and diabetes) would include 37% of the general population, but the prevalence is then too low for screening to be considered cost-effective. Screening using a test with initial automated classification followed by assessment by a specialised optometrist, for test positives, was more cost-effective than initial specialised optometric assessment. The cost-effectiveness of the screening programme was highly sensitive to the perspective on costs (NHS or societal). In the base-case model, the NHS costs of visual impairment were estimated as 669 pounds. If annual societal costs were 8800 pounds, then screening might be considered cost-effective for a 40-year-old cohort with 1% OAG prevalence assuming a willingness to pay of 30,000 pounds per quality-adjusted life-year. Of lesser importance were changes to estimates of attendance for sight tests, incidence of OAG, rate of progression and utility values for each stage of OAG severity. Cost-effectiveness was not particularly sensitive to the accuracy of screening tests within the ranges observed. However, a highly specific test is required to reduce large numbers of false-positive referrals. The findings that population screening is unlikely to be cost-effective are based on an economic model whose parameter estimates have considerable uncertainty. In particular, if rate of progression and/or costs of visual impairment are higher than estimated then screening could be cost-effective. CONCLUSIONS: While population screening is not cost-effective, the targeted screening of high-risk groups may be. Procedures for identifying those at risk, for quality assuring the programme, as well as adequate service provision for those screened positive would all be needed. Glaucoma detection can be improved by increasing attendance for eye examination, and improving the performance of current testing by either refining practice or adding in a technology-based first assessment, the latter being the more cost-effective option. This has implications for any future organisational changes in community eye-care services. Further research should aim to develop and provide quality data to populate the economic model, by conducting a feasibility study of interventions to improve detection, by obtaining further data on costs of blindness, risk of progression and health outcomes, and by conducting an RCT of interventions to improve the uptake of glaucoma testing.

Journal ArticleDOI
25 May 2007-Science
TL;DR: This work reports that CB1 cannabinoid receptors are enriched in the axonal growth cones of γ-aminobutyric acid–containing interneurons in the rodent cortex during late gestation and demonstrates that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.
Abstract: The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB(1) cannabinoid receptors (CB(1)Rs) are enriched in the axonal growth cones of gamma-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB(1)R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB(1)Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.

Journal ArticleDOI
TL;DR: The recent turn to "strategy practice" offers a genuine opportunity for establishing an alternative perspective that is clearly distinct from the traditional strategy process view as discussed by the authors, and the challenge is to clarify and articulate an alternative set of ontological and epistemological premises for founding this new approach to theorizing strategy.
Abstract: The recent turn to ‘strategy practice’ offers a genuine opportunity for establishing an alternative perspective that is clearly distinct from the traditional strategy process view. The challenge is to clarify and articulate an alternative set of ontological and epistemological premises for founding this new approach to theorizing strategy.What has been called the ‘practice turn’ in social theory provides this alternative basis for a ‘post-processual’ approach to theorizing strategy-as-practice. This ‘practice turn’ involves a radical reformulation of the intractable problem of agency and structure that enables us to bypass the ‘micro/macro’ distinction so intimately tied to the social sciences in general and to strategy research in particular. Already, there are signs that the discourse of the strategy-as-practice research community reflects this awareness and are thus straining towards some form of ‘trans-individual’ explanation that is not restricted to the mere ‘activities’ of strategy actors nor to th...

Journal ArticleDOI
TL;DR: The underlying theme of this Critical Review is the relationship between molecular structure and liquid crystalline behaviour in a class of materials referred to as liquid crystal oligomers, and how this molecular architecture has been exploited to address issues in a range of quite different areas and has given rise to potential applications for these materials.
Abstract: The underlying theme of this Critical Review is the relationship between molecular structure and liquid crystalline behaviour in a class of materials referred to as liquid crystal oligomers. For the purposes of this review, a liquid crystal oligomer will be defined as consisting of molecules composed of semi-rigid mesogenic units connected via flexible spacers. Much of the review will be devoted to structure–property relationships in the simplest oligomers, namely dimers, in which just two mesogenic units are connected by a single spacer. Along the way we will see how this molecular architecture has been exploited to address issues in a range of quite different areas and has given rise to potential applications for these materials. On the whole, only compounds in which the mesogenic units are linked essentially in a linear fashion will be considered while structures such as liquid crystal dendrimers and tetrapodes fall outside the scope of this review. The review will be of interest not only to scientists working directly in this area but in particular to those interested in understanding the relationships between structure and properties in polymers, and those designing materials for new applications (231 references).

Journal ArticleDOI
TL;DR: The principal strength of this cohort is the rarely captured phenotype of lifetime cognitive change, which is important in alerting other researchers to the data available in the cohort.
Abstract: Background: Cognitive ageing is a major burden for society and a major influence in lowering people's independence and quality of life. It is the most feared aspect of ageing. There are large individual differences in age-related cognitive changes. Seeking the determinants of cognitive ageing is a research priority. A limitation of many studies is the lack of a sufficiently long period between cognitive assessments to examine determinants. Here, the aim is to examine influences on cognitive ageing between childhood and old age. Methods/Design: The study is designed as a follow-up cohort study. The participants comprise surviving members of the Scottish Mental Survey of 1947 (SMS1947; N = 70,805) who reside in the Edinburgh area (Lothian) of Scotland. The SMS1947 applied a valid test of general intelligence to all children born in 1936 and attending Scottish schools in June 1947. A total of 1091 participants make up the Lothian Birth Cohort 1936. They undertook: a medical interview and examination; physical fitness testing; extensive cognitive testing (reasoning, memory, speed of information processing, and executive function); personality, quality of life and other psycho-social questionnaires; and a food frequency questionnaire. They have taken the same mental ability test (the Moray House Test No. 12) at age 11 and age 70. They provided blood samples for DNA extraction and testing and other biomarker analyses. Here we describe the background and aims of the study, the recruitment procedures and details of numbers tested, and the details of all examinations.

Journal ArticleDOI
TL;DR: In this paper, an interpretational framework for the analysis of a diverse set of geological structures that breach sealing sequences and allow fluids to flow vertically or subvertically across the seal.
Abstract: We present an interpretational framework for the analysis of a diverse set of geological structures that breach sealing sequences and allow fluids to flow vertically or subvertically across the seal. In so doing, they act as seal bypass systems (SBS). We define SBS as seismically resolvable geological features embedded within sealing sequences that promote cross-stratal fluid migration and allow fluids to bypass the pore network. If such bypass systems exist within a given seal sequence, then predictions of sealing capacity based exclusively on the flow properties (capillary entry pressure and hydraulic conductivity) of the bulk rock can potentially be negated by the capacity of the bypass system to breach the grain and pore network. We present a range of examples of SBS affecting contrasting types of sealing sequences using three-dimensional (3-D) seismic data. These examples show direct evidence of highly focused vertical or subvertical fluid flow from subsurface reservoirs up through the seal sequence, with leakage internally at higher levels or to the surface as seeps.We classify SBS into three main groups based on seismic interpretational criteria: (1) fault related, (2) intrusion related, and (3) pipe related. We show how each group exhibits different modes of behavior with different scaling relationships between flux and dimensions and different short- and long-term impacts on seal behavior.

Journal ArticleDOI
TL;DR: The deleterious neurobiological processes that underpin depression, anxiety and psychosis may interact with those producing seizures to increase the extent of brain dysfunction and thereby the likelihood of developing pharmacoresistant epilepsy.

Journal ArticleDOI
TL;DR: There is insufficient evidence on the effect of BMI on live birth, cycle cancellation, oocyte recovery and ovarian hyperstimulation syndrome, and further studies with clear entry criteria and uniform reporting of outcomes are needed to investigate the true impact of weight.
Abstract: Obesity is known to be associated with sub-optimal reproductive performance but its direct effect on the outcome of assisted reproduction techniques (ART) is less clear. This present study aimed to perform a systematic review of the available evidence to assess the effects of obesity on the outcome of ART. A number of observational studies were identified. Interpretation of the results was compromised by variations in the methods used to define overweight and obese populations and inconsistencies in the choice and definition of outcome measures. Compared with women with a BMI of 25 kg/m(2) or less, women with a BMI > or = 25 kg/m(2) have a lower chance of pregnancy following IVF [odds ratio (OR) 0.71, 95% CI: 0.62, 0.81], require higher dose of gonadotrophins (weighed mean differences 210.08, 95% CI: 149.12, 271.05) and have an increased miscarriage rate (OR 1.33, 95% CI: 1.06, 1.68). There is insufficient evidence on the effect of BMI on live birth, cycle cancellation, oocyte recovery and ovarian hyperstimulation syndrome. Further studies with clear entry criteria and uniform reporting of outcomes are needed to investigate the true impact of weight on the outcome of ART.

Journal ArticleDOI
06 Jul 2007-Science
TL;DR: It is argued—and data is reported suggesting—that stimulus-independent thought dominates unconstrained cognitive periods, and activity in the default network may be due to the emergence of stimulus-oriented rather than stimulus- independent thought.
Abstract: Gilbert et al. suggest that activity in the default network may be due to the emergence of stimulus-oriented rather than stimulus-independent thought. Although both kinds of thought likely emerge during familiar tasks, we argue—and report data suggesting—that stimulus-independent thought dominates unconstrained cognitive periods.

Journal ArticleDOI
TL;DR: It is suggested that future trials should consider the different needs at different phases in the life of trials, and place greater emphasis on 'conduct' (the process of actually doing trials).
Abstract: Objectives To identify factors associated with good and poor recruitment to multicentre trials. Data sources Part A: database of trials started in or after 1994 and were due to end before 2003 held by the Medical Research Council and Health Technology Assessment Programmes. Part B: interviews with people playing a wide range of roles within four trials that their funders identified as 'exemplars'. Part C: a large multicentre trial (the CRASH trial) of treatment for head injury. Review methods The study used a number of different perspectives ('multiple lenses'), and three components. Part A: an epidemiological review of a cohort of trials. Part B: case studies of trials that appeared to have particularly interesting lessons for recruitment. Part C: a single, in-depth case study to examine the feasibility of applying a business-orientated analytical framework as a reference model in future trials. Results In the 114 trials found in Part A, less than one-third recruited their original target within the time originally specified, and around one-third had extensions. Factors observed more often in trials that recruited successfully were: having a dedicated trial manager, being a cancer or drug trial, and having interventions only available inside the trial. The most commonly reported strategies to improve recruitment were newsletters and mailshots, but it was not possible to assess whether they were causally linked to changes in recruitment. The analyses in Part B suggested that successful trials were those addressing clinically important questions at a timely point. The investigators were held in high esteem by the interviewees, and the trials were firmly grounded in existing clinical practices, so that the trial processes were not alien to clinical collaborators, and the results could be easily applicable to future practice. The interviewees considered that the needs of patients were well served by participation in the trials. Clinical collaborators particularly appreciated clear delineation of roles, which released them from much of the workload associated with trial participation. There was a strong feeling from interviewees that they were proud to be part of a successful team. This pride fed into further success. Good groundwork and excellent communications across many levels of complex trial structures were considered to be extremely important, including training components for learning about trial interventions and processes, and team building. All four trials had faced recruitment problems, and extra insights into the working of trials were afforded by strategies invoked to address them. The process of the case study in Part C was able to draw attention to a body of research and practice in a different discipline (academic business studies). It generated a reference model derived from a combination of business theory and work within CRASH. This enabled identification of weaker managerial components within CRASH, and initiatives to strengthen them. Although it is not clear, even within CRASH, whether the initiatives that follow from developing and applying the model will be effective in increasing recruitment or other aspects of the success of the trial, the reference model could provide a template, with potential for those managing other trials to use or adapt it, especially at foundation stages. The model derived from this project could also be used as a diagnostic tool if trials have difficulties and hence as a basis for deciding what type of remedial action to take. It may also be useful for auditing the progress of trials, such as during external review. Conclusions While not producing sufficiently definitive results to make strong recommendations, the work here suggests that future trials should consider the different needs at different phases in the life of trials, and place greater emphasis on 'conduct' (the process of actually doing trials). This implies learning lessons from successful trialists and trial managers, with better training for issues relating to trial conduct. The complexity of large trials means that unanticipated difficulties are highly likely at some time in every trial. Part B suggested that successful trials were those flexible and robust enough to adapt to unexpected issues. Arguably, the trialists should also expect agility from funders within a proactive approach to monitoring ongoing trials. Further research into different recruitment patterns (including 'failures') may help to clarify whether the patterns seen in the 'exemplar' trials differ or are similar. The reference model from Part C needs to be further considered in other similar and different trials to assess its robustness. These and other strategies aimed at increasing recruitment and making trials more successful need to be formally evaluated for their effectiveness in a range of trials.

Journal ArticleDOI
TL;DR: One SNP, rs6920220, was unequivocally replicated in a validation study, as described here, and maps to 6q23, between the genes oligodendrocyte lineage transcription factor 3 (OLIG3) and tumor necrosis factor-α–induced protein 3 (TNFAIP3).
Abstract: The Wellcome Trust Case Control Consortium (WTCCC) identified nine single SNPs putatively associated with rheumatoid arthritis at P = 1 x 10(-5) - 5 x 10(-7) in a genome-wide association screen. One, rs6920220, was unequivocally replicated (trend P = 1.1 x 10(-8)) in a validation study, as described here. This SNP maps to 6q23, between the genes oligodendrocyte lineage transcription factor 3 (OLIG3) and tumor necrosis factor-alpha-induced protein 3 (TNFAIP3).

Journal ArticleDOI
TL;DR: In this article, the relationship between soil organic carbon (SOC) pools used in RothC and fractions separated through a fractionation procedure was tested using 123 topsoil samples from agricultural sites (arable land, grassland and alpine pasture) across Switzerland.
Abstract: Summary Understanding the response of soil organic carbon (SOC) to environmental and management factors is necessary for estimating the potential of soils to sequester atmospheric carbon. Changes over time in the amount and distribution of SOC fractions with different turnover rates can be estimated by means of soil SOC models such as RothC, which typically consider two to five SOC pools. Ideally, these pools should correspond to measurable SOC fractions. The aim of this study was to test the relationship between SOC pools used in RothC and fractions separated through a fractionation procedure. A total of 123 topsoil samples from agricultural sites (arable land, grassland and alpine pasture) across Switzerland were used. A combination of physical and chemical methods resulted in two sensitive (particulate organic matter and dissolved organic carbon), two slow (carbon associated to clay and silt or stabilized in aggregates) and one passive (oxidation-resistant carbon) SOM fractions. These fractions were compared with the estimated equilibrium model pools when the corresponding soils were modelled with RothC. Analysis revealed strong correlations between SOC in measured fractions and modelled pools. Spearman’s rank correlation coefficients varied between 0.82 for decomposable plant materials (DPM), 0.76 for resistant plant materials (RPM), 0.99 for humified organic matter (HUM) and biomass (BIO), and 0.73 for inert organic matter (IOM). The results show that the proposed fractionation procedure can be used with minor adaptations to identify measurable SOC fractions, which can be used to initialize and evaluate RothC for a wide range of site conditions.