The challenges for molecular nutrition research 1: linking genotype to healthy nutrition

Nutrition science finds itself at a major crossroad. On the one hand we can continue the current path, which has resulted in some substantial advances, but also many conflicting messages which impair the trust of the general population, especially those who are motivated to improve their health through diet. The other road is uncharted and is being built over the many exciting new developments in life sciences. This new era of nutrition recognizes the complex relation between the health of the individual, its genome, and the life-long dietary exposure, and has lead to the realisation that nutrition is essentially a gene - environment interaction science. This review on the relation between genotype, diet and health is the first of a series dealing with the major challenges in molecular nutrition, analyzing the foundations of nutrition research. With the unravelling of the human genome and the linking of its variability to a multitude of phenotypes from " healthy'' to an enormously complex range of predispositions, the dietary modulation of these propensities has become an area of active research. Classical genetic approaches applied so far in medical genetics have steered away from incorporating dietary effects in their models and paradoxically, most genetic studies analyzing diet-associated phenotypes and diseases simply ignore diet. Yet, a modest but increasing number of studies are accounting for diet as a modulator of genetic associations. These range from observational cohorts to intervention studies with prospectively selected genotypes. New statistical and bioinformatics approaches are becoming available to aid in design and evaluation of these studies. This review discusses the various approaches used and provides concrete recommendations for future research.

Protocol for the PINCER trial: a cluster randomised trial comparing the 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 are an important cause of morbidity and mortality in primary care. The aims of this study are to determine the effectiveness, cost effectiveness and acceptability of a pharmacist-led information-technology-based complex intervention compared with simple feedback in reducing proportions of patients at risk from potentially hazardous prescribing and medicines management in general (family) practice. Methods: Research subject group: "At-risk" patients registered with computerised general practices in two geographical regions in England. Design: Parallel group pragmatic cluster randomised trial. Interventions: Practices will be randomised to either: (i) Computer-generated feedback; or (ii) Pharmacist-led intervention comprising of computer-generated feedback, educational outreach and dedicated support. Primary outcome measures: The proportion of patients in each practice at six and 12 months post intervention: - with a computer-recorded history of peptic ulcer being prescribed non-selective non-steroidal anti-inflammatory drugs - with a computer-recorded diagnosis of asthma being prescribed beta-blockers - aged 75 years and older receiving long-term prescriptions for angiotensin converting enzyme inhibitors or loop diuretics without a recorded assessment of renal function and electrolytes in the preceding 15 months. Secondary outcome measures; These relate to a number of other examples of potentially hazardous prescribing and medicines management. Economic analysis: An economic evaluation will be done of the cost per error avoided, from the perspective of the UK National Health Service (NHS), comparing the pharmacist-led intervention with simple feedback. Qualitative analysis: A qualitative study will be conducted to explore the views and experiences of health care professionals and NHS managers concerning the interventions, and investigate possible reasons why the interventions prove effective, or conversely prove ineffective. Sample size: 34 practices in each of the two treatment arms would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a 50% reduction in error rates for each of the three primary outcome measures in the pharmacist-led intervention arm compared with a 11% reduction in the simple feedback arm. Discussion: At the time of submission of this article, 72 general practices have been recruited (36 in each arm of the trial) and the interventions have been delivered. Analysis has not yet been undertaken.

Adapting to climate change: an evolving research programme

Since its launch in 1977, the scientific issues addressed by papers published in Climatic Change have changed considerably. Nuclear winter came and went, and papers have come from an increasingly diverse range of disciplines. Most obvious, of course, has been the emergence to overwhelming dominance of papers concerned with the processes and consequences associated with the climate changes driven by increasing human emissions of greenhouse gases. Within this theme too, it is possible to track the evolution of different topics over the last thirty years. In the pages of Climatic Change, as within the climate change research community, increased attention has been given to adaptation to a changing climate. Here, I examine the scale and characteristics of adaptation research in Climatic Change, draw some general conclusions from the research published in Climatic Change, and suggest from this some future research directions.

Actors and objects: A socio-technical networks approach for construction management research

We explore the contribution of socio-technical networks approaches to construction management research. These approaches are distinctive for their analysis of actors and objects as mutually constituted within socio-technical networks. They raise questions about the ways in which the content, meaning and use of technology is negotiated in practice, how particular technical configurations are elaborated in response to specific problems and why certain paths or solutions are adopted rather than others. We illustrate this general approach with three case studies: a historical study of the development of reinforced concrete in France, the UK and the US, the recent introduction of 3D-CAD software into four firms and an analysis of the uptake of environmental assessment technologies in the UK since 1990. In each we draw out the ways in which various technologies shaped and were shaped by different socio-technical networks. We conclude with a reflection on the contributions of socio-technical network analysis for more general issues including the study of innovation and analyses of context and power.

A simple relationship between volcanic sulfate aerosol optical depth and surface temperature change simulated in an atmosphere-ocean general circulation model.

In this study we quantify the relationship between the aerosol optical depth increase from a volcanic eruption and the severity of the subsequent surface temperature decrease. This investigation is made by simulating 10 different sizes of eruption in a global circulation model (GCM) by changing stratospheric sulfate aerosol optical depth at each time step. The sizes of the simulated eruptions range from Pinatubo‐sized up to the magnitude of supervolcanic eruptions around 100 times the size of Pinatubo. From these simulations we find that there is a smooth monotonic relationship between the global mean maximum aerosol optical depth anomaly and the global mean temperature anomaly and we derive a simple mathematical expression which fits this relationship well. We also construct similar relationships between global mean aerosol optical depth and the temperature anomaly at every individual model grid box to produce global maps of best‐fit coefficients and fit residuals. These maps are used with caution to find the eruption size at which a local temperature anomaly is clearly distinct from the local natural variability and to approximate the temperature anomalies which the model may simulate following a Tambora‐sized eruption. To our knowledge, this is the first study which quantifies the relationship between aerosol optical depth and resulting temperature anomalies in a simple way, using the wealth of data that is available from GCM simulations.

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.

Electromagnetic atmosphere-plasma coupling: the global atmospheric electric circuit

A description is given of the global atmospheric electric circuit operating between the Earth’s surface and the ionosphere. Attention is drawn to the huge range of horizontal and vertical spatial scales, ranging from 10−9 m to 1012 m, concerned with the many important processes at work. A similarly enormous range of time scales is involved from 10−6 s to 109 s, in the physical effects and different phenomena that need to be considered. The current flowing in the global circuit is generated by disturbed weather such as thunderstorms and electrified rain/shower clouds, mostly occurring over the Earth’s land surface. The profile of electrical conductivity up through the atmosphere, determined mainly by galactic cosmic ray ionization, is a crucial parameter of the circuit. Model simulation results on the variation of the ionospheric potential, ∼250 kV positive with respect to the Earth’s potential, following lightning discharges and sprites are summarized. Experimental results comparing global circuit variations with the neutron rate recorded at Climax, Colorado, are then discussed. Within the return (load) part of the circuit in the fair weather regions remote from the generators, charge layers exist on the upper and lower edges of extensive layer clouds; new experimental evidence for these charge layers is also reviewed. Finally, some directions for future research in the subject are suggested.

Pollination ecology in the 21st century: key questions for future research

To inspire new ideas in research on pollination ecology, we list the most important unanswered questions in the field. This list was drawn up by contacting 170 scientists from different areas of pollination ecology and asking them to contribute their opinion on the greatest knowledge gaps that need to be addressed. Almost 40% of them took part in our email poll and we received more than 650 questions and comments, which we classified into different categories representing various aspects of pollination research. The original questions were merged and synthesised, and a final vote and ranking led to the resultant list. The categories cover plant sexual reproduction, pollen and stigma biology, abiotic pollination, evolution of animal-mediated pollination, interactions of pollinators and floral antagonists, pollinator behaviour, taxonomy, plant-pollinator assemblages, geographical trends in diversity, drivers of pollinator loss, ecosystem services, management of pollination, and conservation issues such as the implementation of pollinator conservation. We focused on questions that were of a broad scope rather than case-specific; thus, addressing some questions may not be feasible within single research projects but constitute a general guide for future directions. With this compilation we hope to raise awareness of pollination-related topics not only among researchers but also among non-specialists including policy makers, funding agencies and the public at large.

Motivation in second language acquisition in Chinese research students in the UK

The present study sets out to examine motivation to learn English by Chinese research students in an informal setting. Data were collected, using semi-structured interviews, from four research students at two points in time during their first year in the UK. The main findings are: they believed that learning English was important; their main goal orientations were instrumental and extrinsic; they set learning goals and persisted to attain them; they valued their current learning environment in general and saw it as supportive of their goals; they held both positive and negative attitudes towards the British, which had differential effects on their motivation; their self-perceived support seemed to have a positive impact on their motivation and the development of self-confidence; they tended to attribute their success to stable causes such as the environment and failure to unstable but controllable causes such as effort. It is concluded that qualitative data of this kind may complement insights from quantitative research. Implications for target country institutions in the provision of support are discussed.

Re-thinking stakeholder management in construction: theory & research

From its roots in strategic management theory, stakeholder management has been adopted by the construction management academic community and applied as a valid paradigm around which research work has been generated aiming to improve project effi ciencies and effectiveness. However, academics have argued that stakeholder management should move away from purely theoretical discussions and engage more with the realities of construction project work. This paper re-appraises the stakeholder management concept for the construction domain by re-thinking some of the fundamental principles and ideals present within the more general stakeholder theory literature. It engages with issues which researchers have arguably failed to acknowledge and calls for a re-evaluation of construction stakeholder management research by presenting a review around four distinctive themes: the moral obligations of engaging with stakeholders against the business and efficiency driven imperatives of construction organisations; the contrast between theoretical abstractions and empirically grounded research; the tensions between theoretical convergence versus calls for multiple and divergent perspectives on stakeholder management and the practicalities of conducting stakeholder management in the construction domain. Such a critical re-appraisal of stakeholder management thinking both generates new lines of enquiry and promises to help inform and shape current and future industry practice.

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.

Traditional Chinese medicine research in the post-genomic era: good practice, priorities, challenges and opportunities

Background and aims: GP-TCM is the 1st EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. This paper aims to summarise the objectives, structure and activities of the consortium and introduces the position of the consortium regarding good practice, priorities, challenges and opportunities in TCM research. Serving as the introductory paper for the GPTCM Journal of Ethnopharmacology special issue, this paper describes the roadmap of this special issue and reports how the main outputs of the ten GP-TCM work packages are integrated, and have led to consortium-wide conclusions. Materials and methods: Literature studies, opinion polls and discussions among consortium members and stakeholders. Results: By January 2012, through 3 years of team building, the GP-TCM consortium had grown into a large collaborative network involving ∼200 scientists from 24 countries and 107 institutions. Consortium members had worked closely to address good practice issues related to various aspects of Chinese herbal medicine (CHM) and acupuncture research, the focus of this Journal of Ethnopharmacology special issue, leading to state-of-the-art reports, guidelines and consensus on the application of omics technologies in TCM research. In addition, through an online survey open to GP-TCM members and non-members, we polled opinions on grand priorities, challenges and opportunities in TCM research. Based on the poll, although consortium members and non-members had diverse opinions on the major challenges in the field, both groups agreed that high-quality efficacy/effectiveness and mechanistic studies are grand priorities and that the TCM legacy in general and its management of chronic diseases in particular represent grand opportunities. Consortium members cast their votes of confidence in omics and systems biology approaches to TCM research and believed that quality and pharmacovigilance of TCM products are not only grand priorities, but also grand challenges. Non-members, however, gave priority to integrative medicine, concerned on the impact of regulation of TCM practitioners and emphasised intersectoral collaborations in funding TCM research, especially clinical trials. Conclusions: The GP-TCM consortium made great efforts to address some fundamental issues in TCM research, including developing guidelines, as well as identifying priorities, challenges and opportunities. These consortium guidelines and consensus will need dissemination, validation and further development through continued interregional, interdisciplinary and intersectoral collaborations. To promote this, a new consortium, known as the GP-TCM Research Association, is being established to succeed the 3-year fixed term FP7 GP-TCM consortium and will be officially launched at the Final GP-TCM Congress in Leiden, the Netherlands, in April 2012.

Toward a new generation of world climate research and computing facilities

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.