Large Collaborative Project Research Articles

Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement

The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance....

Measurement of radiated underwater noise from a small research vessel in shallow water

The impact of man-made underwater noise on the marine environment has recently received increased attention from regulatory authorities, as evidenced by inclusion in the Marine Strategy Framework Directive (MSFD). Radiated underwater noise from ships, primarily resulting from propeller cavitation, has for many years been understood to be one of the major contributors to ambient ocean noise. Civilian research in this area has to date been relatively limited; standards covering the measurement of radiated noise from ships in deep water and associated data analysis procedures have only recently been published by national and international standards institutes. Less attention has so far been paid to the measurement of radiated noise from ships in shallow water environments. This is of interest as shallow water areas are more likely to be used by civilian researchers due to the logistical problems involved in undertaking trials in deep water. The issue of shipping noise has been identified as one requiring further research, indicated by the recent funding of several large collaborative projects by the EU (e.g. the SILENV, AQUO and SONIC projects). This paper presents ship radiated noise data measured using a three hydrophone array during a sea trial undertaken as part of the SONIC project.

The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results.

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network.

Exploring Meaningfully and Creatively the Tensions Arising out of Collaborations: An Anthropological Perspective

The issue of working with a set agenda, designed by a larger collaborative project, is core to this article. By using my own experience, I will consider the ways in which established project themes can influence and shape the open-ended method of anthropological research and the final outcome. Additionally, this article will contemplate upon dilemmas of being a young anthropologist while seeking to gain ethnographic authority within a collaborative scenario outside the discipline of anthropology.

School leadership and capacity building in Kazakhstan

The article examines the scope for initiative and independent action that lies with school principals in Kazakhstan, with a particular focus on capacity-building approaches. The study is situated within a large collaborative project between three institutions: the University of Cambridge Faculty of Education, Nazarbayev University Graduate School of Education and Nazarbayev Intellectual Schools (NIS). A mixed-methods research design was used to collect data in 20 schools and 11 other educational organizations in six different geographical locations in Kazakhstan. The findings suggest that capacity-building strategies are necessary if innovations are to be implemented across all schools. The article outlines the challenges involved in making school reform effective and draws on the ‘capital framework’. The conclusion considers the implications for practitioners and policy-makers, and outlines an agenda for further research.

The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.

Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma.

Background:Oesophageal adenocarcinoma (OAC) is one of the fastest rising malignancies with continued poor prognosis. Many studies have proposed novel biomarkers but, to date, no immunohistochemical markers of survival after oesophageal resection have entered clinical practice. Here, we systematically review and meta-analyse the published literature, to identify potential biomarkers.Methods:Relevant articles were identified via Ovid medline 1946–2013. For inclusion, studies had to conform to REporting recommendations for tumor MARKer (REMARK) prognostic study criteria. The primary end-point was a pooled hazard ratio (HR) and variance, summarising the effect of marker expression on prognosis.Results:A total of 3059 articles were identified. After exclusion of irrelevant titles and abstracts, 214 articles were reviewed in full. Nine molecules had been examined in more than one study (CD3, CD8, COX-2, EGFR, HER2, Ki67, LgR5, p53 and VEGF) and were meta-analysed. Markers with largest survival effects were COX-2 (HR=2.47, confidence interval (CI)=1.15–3.79), CD3 (HR=0.51, 95% CI=0.32–0.70), CD8 (HR=0.55, CI=0.31–0.80) and EGFR (HR=1.65, 95% CI=1.14–2.16).Discussion:Current methods have not delivered clinically useful molecular prognostic biomarkers in OAC. We have highlighted the paucity of good-quality robust studies in this field. A genome-to-protein approach would be better suited for the development and subsequent validation of biomarkers. Large collaborative projects with standardised methodology will be required to generate clinically useful biomarkers.

Time to face the challenge of multimorbidity. A European perspective from the joint action on chronic diseases and promoting healthy ageing across the life cycle (JA-CHRODIS)

Research on multimorbidity has rapidly increased in the last decade, but evidence on the effectiveness of interventions to improve outcomes in patients with multimorbidity is limited. The European Commission is co-funding a large collaborative project named Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) in the context of the 2nd EU Health Programme 2008–2013. The present manuscript summarizes first results of the JA-CHRODIS, focuses on the identification of a population with multimorbidity who has a high or very high care demand. Identification of characteristics of multimorbid patients associated with a high rate of resource consumption and negative health outcomes is necessary to define a target population who can benefit from interventions. Indeed, multimorbidity alone cannot explain the complexity of care needs and further, stratification of the general population based on care needs is necessary for allocating resources and developing personalized, cost-efficient, and patient-centered care plans. Based on analyses of large databases from European countries a profile of the most care-demanding patients with multimorbidity is defined. Several factors associated with adverse health outcomes and resource consumption among patients with multimorbidity were identified in these analyses, including disease patterns, physical function, mental health, and socioeconomic status. These results underline that a global assessment is needed to identify patients with multimorbidity who are at risk of negative health outcomes and that a comprehensive approach, targeting not only diseases, but also social, cognitive, and functional problems should be adopted for these patients.

Addressing ethical issues in H3Africa research – the views of research ethics committee members

In June 2014, the H3Africa Working Group on Ethics organised a workshop with members of over 40 research ethics committees from across Africa to discuss the ethical challenges raised in H3Africa research, and to receive input on the proposed H3Africa governance framework. Prominent amongst a myriad of ethical issues raised by meeting participants were concerns over consent for future use of samples and data, the role of community engagement in large international collaborative projects, and particular features of the governance of sample sharing. This report describes these concerns in detail and will be informative to researchers wishing to conduct genomic research on diseases pertinent to the African research context.

Architectures of adaptive integration in large collaborative projects

Architectures of adaptive integration in large collaborative projects

A COMPLEX NETWORKS PERSPECTIVE ON COLLABORATIVE SOFTWARE ENGINEERING

Large collaborative software engineering projects are interesting examples for evolving complex systems. The complexity of these systems unfolds both in evolving software structures, as well as in the social dynamics and organization of development teams. Due to the adoption of Open Source practices and the increasing use of online support infrastructures, large-scale data sets covering both the social and technical dimension of collaborative software engineering processes are increasingly becoming available. In the analysis of these data, a growing number of studies employ a network perspective, using methods and abstractions from network science to generate insights about software engineering processes. Featuring a collection of inspiring works in this area, with this topical issue, we intend to give an overview of state-of-the-art research. We hope that this collection of articles will stimulate downstream applications of network-based data mining techniques in empirical software engineering.

Unconventional animal models: a booster for new advances in host-pathogen interactions.

OPINION article Front. Cell. Infect. Microbiol., 08 October 2014Sec. Clinical Microbiology Volume 4 - 2014 | https://doi.org/10.3389/fcimb.2014.00142

Normalization of RNA-seq data using factor analysis of control genes or samples.

Normalization of RNA-sequencing (RNA-seq) data has proven essential to ensure accurate inference of expression levels. Here, we show that usual normalization approaches mostly account for sequencing depth and fail to correct for library preparation and other more complex unwanted technical effects. We evaluate the performance of the External RNA Control Consortium (ERCC) spike-in controls and investigate the possibility of using them directly for normalization. We show that the spike-ins are not reliable enough to be used in standard global-scaling or regression-based normalization procedures. We propose a normalization strategy, called remove unwanted variation (RUV), that adjusts for nuisance technical effects by performing factor analysis on suitable sets of control genes (e.g., ERCC spike-ins) or samples (e.g., replicate libraries). Our approach leads to more accurate estimates of expression fold-changes and tests of differential expression compared to state-of-the-art normalization methods. In particular, RUV promises to be valuable for large collaborative projects involving multiple laboratories, technicians, and/or sequencing platforms.

Sudden death in adult congenital heart disease: risk stratification in 2014.

Arrhythmias and sudden death continue to plague a subset of adult patients with congenital heart disease. Despite investigative efforts spanning many decades, accurate identification of the high-risk patient remains challenging owing to a limited population size, relatively low event rate, and constantly evolving surgical approaches to the various malformations. Furthermore, until recently, most studies of the subject involved single-center formats with limited statistical power. The number of adult survivors has now reached a critical size where larger collaborative projects are beginning to generate more objective criteria for assessing risk. This review will provide an update on risk stratification for several of the major congenital cardiac lesions and outline the current recommendations for surveillance and management.

The OPtimising HEalth LIterAcy (Ophelia) process: study protocol for using health literacy profiling and community engagement to create and implement health reform.

BackgroundHealth literacy is a multi-dimensional concept comprising a range of cognitive, affective, social, and personal skills and attributes. This paper describes the research and development protocol for a large communities-based collaborative project in Victoria, Australia that aims to identify and respond to health literacy issues for people with chronic conditions. The project, called Ophelia (OPtimising HEalth LIterAcy) Victoria, is a partnership between two universities, eight service organisations and the Victorian Government. Based on the identified issues, it will develop and pilot health literacy interventions across eight disparate health services to inform the creation of a health literacy response framework to improve health outcomes and reduce health inequalities.Methods/DesignThe protocol draws on many inputs including the experience of the partners in previous co-creation and roll-out of large-scale health-promotion initiatives. Three key conceptual models/discourses inform the protocol: intervention mapping; quality improvement collaboratives, and realist synthesis. The protocol is outcomes-oriented and focuses on two key questions: ‘What are the health literacy strengths and weaknesses of clients of participating sites?’, and ‘How do sites interpret and respond to these in order to achieve positive health and equity outcomes for their clients?’. The process has six steps in three main phases. The first phase is a needs assessment that uses the Health Literacy Questionnaire (HLQ), a multi-dimensional measure of health literacy, to identify common health literacy needs among clients. The second phase involves front-line staff and management within each service organisation in co-creating intervention plans to strategically respond to the identified local needs. The third phase will trial the interventions within each site to determine if the site can improve identified limitations to service access and/or health outcomes.DiscussionThere have been few attempts to assist agencies to identify, and respond, in a planned way, to the varied health literacy needs of their clients. This project will assess the potential for targeted, locally-developed health literacy interventions to improve access, equity and outcomes.

Infrastructural Inversion as a Generative Resource in Digital Scholarship

Digital humanities scholarship has regularly challenged characteristic organizational features of academic life in the humanities. For example, it is typically practiced in larger collaborative projects that produce output very different from the traditional scholarly monograph. Digital humanists often present their work in strikingly reflexive accounts that are reminiscent of what science and technology studies scholars have called infrastructural inversion, a method that defamiliarizes the socio-material infrastructure of research to expose the inner workings of knowledge production. At first sight, infrastructural inversion might seem to constitute the opposite of the older concept of articulation work, which designates the situated activity of coordinating and managing cooperative work processes. It is more useful, however, to think about infrastructural inversion as a specific form of articulation work. The inversions performed by digital scholars serve to highlight and problematize established ways of streamlining articulation work, for example, through the established model of peer review, or by using conventional forms of scholarly output. In turn, such systematic defamiliarization opens up new and potentially competing ways of imagining the organization of articulation work.

Discovering Beaten Paths in Collaborative Ontology-Engineering Projects using Markov Chains

Biomedical taxonomies, thesauri and ontologies in the form of the International Classification of Diseases as a taxonomy or the National Cancer Institute Thesaurus as an OWL-based ontology, play a critical role in acquiring, representing and processing information about human health. With increasing adoption and relevance, biomedical ontologies have also significantly increased in size. For example, the 11th revision of the International Classification of Diseases, which is currently under active development by the World Health Organization contains nearly 50,000 classes representing a vast variety of different diseases and causes of death. This evolution in terms of size was accompanied by an evolution in the way ontologies are engineered. Because no single individual has the expertise to develop such large-scale ontologies, ontology-engineering projects have evolved from small-scale efforts involving just a few domain experts to large-scale projects that require effective collaboration between dozens or even hundreds of experts, practitioners and other stakeholders. Understanding the way these different stakeholders collaborate will enable us to improve editing environments that support such collaborations. In this paper, we uncover how large ontology-engineering projects, such as the International Classification of Diseases in its 11th revision, unfold by analyzing usage logs of five different biomedical ontology-engineering projects of varying sizes and scopes using Markov chains. We discover intriguing interaction patterns (e.g., which properties users frequently change after specific given ones) that suggest that large collaborative ontology-engineering projects are governed by a few general principles that determine and drive development. From our analysis, we identify commonalities and differences between different projects that have implications for project managers, ontology editors, developers and contributors working on collaborative ontology-engineering projects and tools in the biomedical domain.

Unsuspected pulmonary embolism in cancer patients: a narrative review with pooled data

Detection of pulmonary embolism (PE) is not uncommon in patients undergoing computed tomography (CT) for routine staging of malignancy. Several studies have been conducted in recent years to evaluate the impact of unsuspected pulmonary embolism (UPE) on the prognosis and management of cancer patients. We aimed at summarizing the available evidence, to improve the understanding of the frequency and clinical significance of UPE in terms of survival, recurrent venous thromboembolism (VTE) and major bleeding. Medline was searched up to the end of September 2013, by using the terms "unsuspected pulmonary embolism" OR "incidental pulmonary embolism" OR "asymptomatic pulmonary embolism". We found 552 out of 35,990 cancer patients diagnosed with UPE (14 studies), for a mean weighted prevalence of 1.82% (95% CI 1.47-2.21). When comparing cancer patients diagnosed with UPE to those presenting with symptomatic PE, we found a pooled OR of 0.96 (95% CI 0.58-1.57) for mortality (3 studies), 0.87 (95% CI 0.47-1.60) for recurrent VTE (4 studies) and 0.90 (95% CI 0.43-1.88) for major bleeding (4 studies). In conclusion, UPE represents a non-infrequent finding on CT scans ordered for reasons other than suspected PE and is a challenging clinical situation in the management of cancer patients. Even if UPE is generally milder in the short term, it may share a similar impact on survival and recurrent VTE, as compared to symptomatic PE. Large collaborative projects and, hopefully, interventional trials are needed to clarify the best management strategies.

Pathophysiology and risk factors of cervical artery dissection

Cervical artery dissection (CeAD) is a major cause of ischemic stroke in young and middle-aged adults, although relatively uncommon in the community. Recent large collaborative projects have provided new insights into mechanisms and risk factors of CeAD. Pathologic changes observed at the media-adventitia border in temporal arteries of CeAD patients suggest a predisposing arterial wall weakness. In large multicenter series of CeAD patients, compared to age-matched healthy controls and patients with an ischemic stroke of another cause, hypertension and migraine, especially without aura, were confirmed as risk factors for CeAD, in addition to cervical trauma and recent infection. Hypercholesterolemia and being overweight were shown to be inversely associated with CeAD. Differences in risk factor profile and structural features between carotid and vertebral dissection suggest that their pathophysiology may partly differ. An association of CeAD with fibromuscular dysplasia and reversible cerebral vasoconstriction syndrome was described. Genetic risk factors of CeAD are still poorly understood. Large cohorts of CeAD patients have refined our understanding of the pathophysiology and risk factors of CeAD, but the molecular mechanisms are still poorly understood. Ongoing high-throughput genetic projects will hopefully provide novel insight into the biological substrate of CeAD.

A conceptual model for data management in the field of ecology

Conceptual models play an important role in identifying the domain under study and establishing an interoperability framework between different scientific groups and tools working on the same or neighboring domains. The importance comes from the fact that the conceptual models describe the target domain in a technology agnostic manner, using domain terminology, considerations, and rules.In this paper we introduce a highly flexible data and metadata structure for biodiversity (and related fields) information management. The model incorporates important concepts needed to develop a proper domain model for managing biodiversity data, e.g., data, data structure, metadata, metadata structure, and semantic descriptions of model elements. The model is designed in UML using the object oriented analysis paradigms. The data management teams of several large collaborative projects as well as those of two research institutes were actively cooperating in the design of the model, thus ensuring that all aspects relevant for these very different projects and institutions are considered and that a high acceptance of the model will ensue.The model supports and encourages reuse and sharing of different elements, making the cross dataset syntheses, comparison, merging and searches easier. The incorporated semantic package helps to annotate dataset's variables and metadata attributes by means of ontologies, taxonomies or thesauri. These annotations can be used for standardization, localization and also for managing the variety of meanings of same or similar variables among community members.The model is currently undergoing its implementation phase and will replace the model used in the current version of BExIS, a data management platform for biodiversity research, when finished.