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1.  Make it better but don't change anything 
With massive amounts of data being generated in electronic format, there is a need in basic science laboratories to adopt new methods for tracking and analyzing data. An electronic laboratory notebook (ELN) is not just a replacement for a paper lab notebook, it is a new method of storing and organizing data while maintaining the data entry flexibility and legal recording functions of paper notebooks. Paper notebooks are regarded as highly flexible since the user can configure it to store almost anything that can be written or physically pasted onto the pages. However, data retrieval and data sharing from paper notebooks are labor intensive processes and notebooks can be misplaced, a single point of failure that loses all entries in the volume. Additional features provided by electronic notebooks include searchable indices, data sharing, automatic archiving for security against loss and ease of data duplication. Furthermore, ELNs can be tasked with additional functions not commonly found in paper notebooks such as inventory control. While ELNs have been on the market for some time now, adoption of an ELN in academic basic science laboratories has been lagging. Issues that have restrained development and adoption of ELN in research laboratories are the sheer variety and frequency of changes in protocols with a need for the user to control notebook configuration outside the framework of professional IT staff support. In this commentary, we will look at some of the issues and experiences in academic laboratories that have proved challenging in implementing an electronic lab notebook.
doi:10.1186/1759-4499-1-5
PMCID: PMC2810290  PMID: 20098591
2.  LabTrove: A Lightweight, Web Based, Laboratory “Blog” as a Route towards a Marked Up Record of Work in a Bioscience Research Laboratory 
PLoS ONE  2013;8(7):e67460.
Background
The electronic laboratory notebook (ELN) has the potential to replace the paper notebook with a marked-up digital record that can be searched and shared. However, it is a challenge to achieve these benefits without losing the usability and flexibility of traditional paper notebooks. We investigate a blog-based platform that addresses the issues associated with the development of a flexible system for recording scientific research.
Methodology/Principal Findings
We chose a blog-based approach with the journal characteristics of traditional notebooks in mind, recognizing the potential for linking together procedures, materials, samples, observations, data, and analysis reports. We implemented the LabTrove blog system as a server process written in PHP, using a MySQL database to persist posts and other research objects. We incorporated a metadata framework that is both extensible and flexible while promoting consistency and structure where appropriate. Our experience thus far is that LabTrove is capable of providing a successful electronic laboratory recording system.
Conclusions/Significance
LabTrove implements a one-item one-post system, which enables us to uniquely identify each element of the research record, such as data, samples, and protocols. This unique association between a post and a research element affords advantages for monitoring the use of materials and samples and for inspecting research processes. The combination of the one-item one-post system, consistent metadata, and full-text search provides us with a much more effective record than a paper notebook. The LabTrove approach provides a route towards reconciling the tensions and challenges that lie ahead in working towards the long-term goals for ELNs. LabTrove, an electronic laboratory notebook (ELN) system from the Smart Research Framework, based on a blog-type framework with full access control, facilitates the scientific experimental recording requirements for reproducibility, reuse, repurposing, and redeployment.
doi:10.1371/journal.pone.0067460
PMCID: PMC3720848  PMID: 23935832
3.  The benefits of integrated systems for managing both samples and experimental data: An opportunity for labs in universities and government research institutions to lead the way 
Currently most biomedical labs in universities and government funded research institutions use paper lab notebooks for recording experimental data and spreadsheets for managing sample data. One consequence is that sample management and documenting experiments are viewed as separate and distinct activities, notwithstanding that samples and aliquots are an integral part of a majority of the experiments carried out by these labs.
Various drivers are pushing labs towards integrated management of sample data and experimental data. These include the ever increasing amounts of both kinds of data, the increasing adoption of online collaborative tools, changing expectations about online communication, and the increasing affordability of electronic lab notebooks and sample management software. There is now an opportunity for smaller labs, which have been slow to move from paper to electronic record keeping, to leapfrog better resourced commercial labs and lead the way in adopting the new generation of tools which permit integrated management of samples and experimental data and a range of tangible benefits to conducting research, including:
1. Fewer lost and mislabelled samples
2. Clearer visualization of relationships between samples and experiments
3. Reduction of experimental error
4. More effective search
5. Productivity gains
6. More efficient use of freezers, leading to cost reduction and enhanced sustainability
7. Improved archiving and enhanced memory at the lab and institutional levels
doi:10.1186/1759-4499-3-2
PMCID: PMC3146905  PMID: 21707999
4.  LabKey Server: An open source platform for scientific data integration, analysis and collaboration 
BMC Bioinformatics  2011;12:71.
Background
Broad-based collaborations are becoming increasingly common among disease researchers. For example, the Global HIV Enterprise has united cross-disciplinary consortia to speed progress towards HIV vaccines through coordinated research across the boundaries of institutions, continents and specialties. New, end-to-end software tools for data and specimen management are necessary to achieve the ambitious goals of such alliances. These tools must enable researchers to organize and integrate heterogeneous data early in the discovery process, standardize processes, gain new insights into pooled data and collaborate securely.
Results
To meet these needs, we enhanced the LabKey Server platform, formerly known as CPAS. This freely available, open source software is maintained by professional engineers who use commercially proven practices for software development and maintenance. Recent enhancements support: (i) Submitting specimens requests across collaborating organizations (ii) Graphically defining new experimental data types, metadata and wizards for data collection (iii) Transitioning experimental results from a multiplicity of spreadsheets to custom tables in a shared database (iv) Securely organizing, integrating, analyzing, visualizing and sharing diverse data types, from clinical records to specimens to complex assays (v) Interacting dynamically with external data sources (vi) Tracking study participants and cohorts over time (vii) Developing custom interfaces using client libraries (viii) Authoring custom visualizations in a built-in R scripting environment.
Diverse research organizations have adopted and adapted LabKey Server, including consortia within the Global HIV Enterprise. Atlas is an installation of LabKey Server that has been tailored to serve these consortia. It is in production use and demonstrates the core capabilities of LabKey Server. Atlas now has over 2,800 active user accounts originating from approximately 36 countries and 350 organizations. It tracks roughly 27,000 assay runs, 860,000 specimen vials and 1,300,000 vial transfers.
Conclusions
Sharing data, analysis tools and infrastructure can speed the efforts of large research consortia by enhancing efficiency and enabling new insights. The Atlas installation of LabKey Server demonstrates the utility of the LabKey platform for collaborative research. Stable, supported builds of LabKey Server are freely available for download at http://www.labkey.org. Documentation and source code are available under the Apache License 2.0.
doi:10.1186/1471-2105-12-71
PMCID: PMC3062597  PMID: 21385461
5.  Molecule database framework: a framework for creating database applications with chemical structure search capability 
Background
Research in organic chemistry generates samples of novel chemicals together with their properties and other related data. The involved scientists must be able to store this data and search it by chemical structure. There are commercial solutions for common needs like chemical registration systems or electronic lab notebooks. However for specific requirements of in-house databases and processes no such solutions exist. Another issue is that commercial solutions have the risk of vendor lock-in and may require an expensive license of a proprietary relational database management system. To speed up and simplify the development for applications that require chemical structure search capabilities, I have developed Molecule Database Framework. The framework abstracts the storing and searching of chemical structures into method calls. Therefore software developers do not require extensive knowledge about chemistry and the underlying database cartridge. This decreases application development time.
Results
Molecule Database Framework is written in Java and I created it by integrating existing free and open-source tools and frameworks. The core functionality includes:
• Support for multi-component compounds (mixtures)
• Import and export of SD-files
• Optional security (authorization)
For chemical structure searching Molecule Database Framework leverages the capabilities of the Bingo Cartridge for PostgreSQL and provides type-safe searching, caching, transactions and optional method level security. Molecule Database Framework supports multi-component chemical compounds (mixtures).
Furthermore the design of entity classes and the reasoning behind it are explained. By means of a simple web application I describe how the framework could be used. I then benchmarked this example application to create some basic performance expectations for chemical structure searches and import and export of SD-files.
Conclusions
By using a simple web application it was shown that Molecule Database Framework successfully abstracts chemical structure searches and SD-File import and export to simple method calls. The framework offers good search performance on a standard laptop without any database tuning. This is also due to the fact that chemical structure searches are paged and cached. Molecule Database Framework is available for download on the projects web page on bitbucket: https://bitbucket.org/kienerj/moleculedatabaseframework.
doi:10.1186/1758-2946-5-48
PMCID: PMC3892073  PMID: 24325762
Chemical structure search; Database; Framework; Open-source
6.  Data Management in the Modern Structural Biology and Biomedical Research Environment 
Modern high-throughput structural biology laboratories produce vast amounts of raw experimental data. The traditional method of data reduction is very simple—results are summarized in peer-reviewed publications, which are hopefully published in high-impact journals. By their nature, publications include only the most important results derived from experiments that may have been performed over the course of many years. The main content of the published paper is a concise compilation of these data, an interpretation of the experimental results, and a comparison of these results with those obtained by other scientists.
Due to an avalanche of structural biology manuscripts submitted to scientific journals, in many recent cases descriptions of experimental methodology (and sometimes even experimental results) are pushed to supplementary materials that are only published online and sometimes may not be reviewed as thoroughly as the main body of a manuscript. Trouble may arise when experimental results are contradicting the results obtained by other scientists, which requires (in the best case) the reexamination of the original raw data or independent repetition of the experiment according to the published description of the experiment. There are reports that a significant fraction of experiments obtained in academic laboratories cannot be repeated in an industrial environment (Begley CG & Ellis LM, Nature 483(7391):531–3, 2012). This is not an indication of scientific fraud but rather reflects the inadequate description of experiments performed on different equipment and on biological samples that were produced with disparate methods. For that reason the goal of a modern data management system is not only the simple replacement of the laboratory notebook by an electronic one but also the creation of a sophisticated, internally consistent, scalable data management system that will combine data obtained by a variety of experiments performed by various individuals on diverse equipment. All data should be stored in a core database that can be used by custom applications to prepare internal reports, statistics, and perform other functions that are specific to the research that is pursued in a particular laboratory.
This chapter presents a general overview of the methods of data management and analysis used by structural genomics (SG) programs. In addition to a review of the existing literature on the subject, also presented is experience in the development of two SG data management systems, UniTrack and LabDB. The description is targeted to a general audience, as some technical details have been (or will be) published elsewhere. The focus is on “data management,” meaning the process of gathering, organizing, and storing data, but also briefly discussed is “data mining,” the process of analysis ideally leading to an understanding of the data. In other words, data mining is the conversion of data into information. Clearly, effective data management is a precondition for any useful data mining. If done properly, gathering details on millions of experiments on thousands of proteins and making them publicly available for analysis—even after the projects themselves have ended—may turn out to be one of the most important benefits of SG programs.
doi:10.1007/978-1-4939-0354-2_1
PMCID: PMC4086192  PMID: 24590705
Databases; Data management; Structural biology; LIMS; PSI; CSGID
7.  A novel collaborative e-learning platform for medical students - ALERT STUDENT 
BMC Medical Education  2014;14:143.
Background
The increasing complexity of medical curricula would benefit from adaptive computer supported collaborative learning systems that support study management using instructional design and learning object principles. However, to our knowledge, there are scarce reports regarding applications developed to meet this goal and encompass the complete medical curriculum. The aim of ths study was to develop and assess the usability of an adaptive computer supported collaborative learning system for medical students to manage study sessions.
Results
A study platform named ALERT STUDENT was built as a free web application. Content chunks are represented as Flashcards that hold knowledge and open ended questions. These can be created in a collaborative fashion. Multiple Flashcards can be combined into custom stacks called Notebooks that can be accessed in study Groups that belong to the user institution. The system provides a Study Mode that features text markers, text notes, timers and color-coded content prioritization based on self-assessment of open ended questions presented in a Quiz Mode. Time spent studying and Perception of knowledge are displayed for each student and peers using charts. Computer supported collaborative learning is achieved by allowing for simultaneous creation of Notebooks and self-assessment questions by many users in a pre-defined Group. Past personal performance data is retrieved when studying new Notebooks containing previously studied Flashcards. Self-report surveys showed that students highly agreed that the system was useful and were willing to use it as a reference tool.
Conclusions
The platform employs various instructional design and learning object principles in a computer supported collaborative learning platform for medical students that allows for study management. The application broadens student insight over learning results and supports informed decisions based on past learning performance. It serves as a potential educational model for the medical education setting that has gathered strong positive feedback from students at our school.
This platform provides a case study on how effective blending of instructional design and learning object principles can be brought together to manage study, and takes an important step towards bringing information management tools to support study decisions and improving learning outcomes.
doi:10.1186/1472-6920-14-143
PMCID: PMC4131539  PMID: 25017028
Medical education; Computer supported collaborative learning; E-learning; Information management; Memory retention; Computer-assisted instruction; Tailored learning; Student-centered learning; Spaced repetition
8.  Essential Roles of ECAT15-2/Dppa2 in Functional Lung Development ▿ †  
Molecular and Cellular Biology  2011;31(21):4366-4378.
Many transcription factors and DNA binding proteins play essential roles in the development of organs in which they are highly and/or specifically expressed. Embryonic stem cell (ESC)-associated transcript 15-1 (ECAT15-1) and ECAT15-2, also known as developmental pluripotency-associated 4 (Dppa4) and Dppa2, respectively, are enriched in mouse ESCs and preimplantation embryos, and their genes encode homologous proteins with a common DNA binding domain known as the SAP motif. Previously, ECAT15-1 was shown to be important in lung development, while it is dispensable in early development. In this study, we generated ECAT15-2 single and ECAT15-1 ECAT15-2 double knockout (double KO) mice and found that almost all mutants, like ECAT15-1 mutants, died around birth with respiratory defects. Paradoxically, the expression of neither ECAT15-1 nor ECAT15-2 was detected in lung organogenesis. Several genes, such as Nkx2-5, Gata4, and Pitx2, were downregulated in the ECAT15-2-null lung. On the other hand, genomic DNA of these genes showed inactive chromatin statuses in ECAT15-2-null ESCs, but not in wild-type ESCs. The chromatin immunoprecipitation (ChIP) assay revealed that ECAT15-2 binds to the regulatory region of Nkx2-5 in ESCs. These data suggest that ECAT15-2 has important roles in lung development, where it is no longer expressed, by leaving epigenetic marks from earlier developmental stages.
doi:10.1128/MCB.05701-11
PMCID: PMC3209334  PMID: 21896782
9.  Building a Virtual Network in a Community Health Research Training Program 
Objective: To describe the experiences, lessons, and implications of building a virtual network as part of a two-year community health research training program in a Canadian province.
Design: An action research field study in which 25 health professionals from 17 health regions participated in a seven-week training course on health policy, management, economics, research methods, data analysis, and computer technology. The participants then returned to their regions to apply the knowledge in different community health research projects. Ongoing faculty consultations and support were provided as needed. Each participant was given a notebook computer with the necessary software, Internet access, and technical support for two years, to access information resources, engage in group problem solving, share ideas and knowledge, and collaborate on projects.
Measurements: Data collected over two years consisted of program documents, records of interviews with participants and staff, meeting notes, computer usage statistics, automated online surveys, computer conference postings, program Web site, and course feedback. The analysis consisted of detailed review and comparison of the data from different sources. NUD*IST was then used to validate earlier study findings.
Results: The ten key lessons are that role clarity, technology vision, implementation staging, protected time, just-in-time training, ongoing facilitation, work integration, participatory design, relationship building, and the demonstration of results are essential ingredients for building a successful network.
Conclusion: This study provides a descriptive model of the processes involved in developing, in the community health setting, virtual networks that can be used as the basis for future research and as a practical guide for managers.
PMCID: PMC61441  PMID: 10887165
10.  First steps towards semantic descriptions of electronic laboratory notebook records 
In order to exploit the vast body of currently inaccessible chemical information held in Electronic Laboratory Notebooks (ELNs) it is necessary not only to make it available but also to develop protocols for discovery, access and ultimately automatic processing. An aim of the Dial-a-Molecule Grand Challenge Network is to be able to draw on the body of accumulated chemical knowledge in order to predict or optimize the outcome of reactions. Accordingly the Network drew up a working group comprising informaticians, software developers and stakeholders from industry and academia to develop protocols and mechanisms to access and process ELN records. The work presented here constitutes the first stage of this process by proposing a tiered metadata system of knowledge, information and processing where each in turn addresses a) discovery, indexing and citation b) context and access to additional information and c) content access and manipulation. A compact set of metadata terms, called the elnItemManifest, has been derived and caters for the knowledge layer of this model. The elnItemManifest has been encoded as an XML schema and some use cases are presented to demonstrate the potential of this approach.
doi:10.1186/1758-2946-5-52
PMCID: PMC3878183  PMID: 24360292
11.  Guidelines for information about therapy experiments: a proposal on best practice for recording experimental data on cancer therapy 
BMC Research Notes  2012;5:10.
Background
Biology, biomedicine and healthcare have become data-driven enterprises, where scientists and clinicians need to generate, access, validate, interpret and integrate different kinds of experimental and patient-related data. Thus, recording and reporting of data in a systematic and unambiguous fashion is crucial to allow aggregation and re-use of data. This paper reviews the benefits of existing biomedical data standards and focuses on key elements to record experiments for therapy development. Specifically, we describe the experiments performed in molecular, cellular, animal and clinical models. We also provide an example set of elements for a therapy tested in a phase I clinical trial.
Findings
We introduce the Guidelines for Information About Therapy Experiments (GIATE), a minimum information checklist creating a consistent framework to transparently report the purpose, methods and results of the therapeutic experiments. A discussion on the scope, design and structure of the guidelines is presented, together with a description of the intended audience. We also present complementary resources such as a classification scheme, and two alternative ways of creating GIATE information: an electronic lab notebook and a simple spreadsheet-based format. Finally, we use GIATE to record the details of the phase I clinical trial of CHT-25 for patients with refractory lymphomas. The benefits of using GIATE for this experiment are discussed.
Conclusions
While data standards are being developed to facilitate data sharing and integration in various aspects of experimental medicine, such as genomics and clinical data, no previous work focused on therapy development. We propose a checklist for therapy experiments and demonstrate its use in the 131Iodine labeled CHT-25 chimeric antibody cancer therapy. As future work, we will expand the set of GIATE tools to continue to encourage its use by cancer researchers, and we will engineer an ontology to annotate GIATE elements and facilitate unambiguous interpretation and data integration.
doi:10.1186/1756-0500-5-10
PMCID: PMC3285520  PMID: 22226027
12.  MyLabStocks: a web-application to manage molecular biology materials 
Yeast (Chichester, England)  2014;31(5):179-184.
Laboratory stocks are the hardware of research. They must be stored and managed with mimimum loss of material and information. Plasmids, oligonucleotides and strains are regularly exchanged between collaborators within and between laboratories. Managing and sharing information about every item is crucial for retrieval of reagents, for planning experiments and for reproducing past experimental results. We have developed a web-based application to manage stocks commonly used in a molecular biology laboratory. Its functionalities include user-defined privileges, visualization of plasmid maps directly from their sequence and the capacity to search items from fields of annotation or directly from a query sequence using BLAST. It is designed to handle records of plasmids, oligonucleotides, yeast strains, antibodies, pipettes and notebooks. Based on PHP/MySQL, it can easily be extended to handle other types of stocks and it can be installed on any server architecture. MyLabStocks is freely available from: https://forge.cbp.ens-lyon.fr/redmine/projects/mylabstocks under an open source licence.
doi:10.1002/yea.3008
PMCID: PMC4019915  PMID: 24643870
yeast strains; plasmids; oligonucleotides; software; laboratory management
13.  MyLabStocks: a web-application to manage molecular biology materials 
Yeast (Chichester, England)  2014;31(5):179-184.
Laboratory stocks are the hardware of research. They must be stored and managed with mimimum loss of material and information. Plasmids, oligonucleotides and strains are regularly exchanged between collaborators within and between laboratories. Managing and sharing information about every item is crucial for retrieval of reagents, for planning experiments and for reproducing past experimental results. We have developed a web-based application to manage stocks commonly used in a molecular biology laboratory. Its functionalities include user-defined privileges, visualization of plasmid maps directly from their sequence and the capacity to search items from fields of annotation or directly from a query sequence using BLAST. It is designed to handle records of plasmids, oligonucleotides, yeast strains, antibodies, pipettes and notebooks. Based on PHP/MySQL, it can easily be extended to handle other types of stocks and it can be installed on any server architecture. MyLabStocks is freely available from: https://forge.cbp.ens-lyon.fr/redmine/projects/mylabstocks under an open source licence.
doi:10.1002/yea.3008
PMCID: PMC4019915  PMID: 24643870
yeast strains; plasmids; oligonucleotides; software; laboratory management
14.  MED34/448: The Networked Health-Care Environment of the Future: Requirements for new human abilities 
The implications of the Internet for health care are increasingly understood as scientists, health workers, patients, and health administrators envision new applications, new means for communicating about health issues, and new ways of accessing pertinent health information at the point of care. It is important to study not only the new technologies themselves, but also to recognize that the optimal use of these technologies requires new skills by users. Not only must both patients and health professionals be taught the basic skills related to use of networking technologies, but those who develop future systems must understand the new human abilities that are implied by the remarkable changes that are envisioned. We describe the results of research that have implications for effectively exploiting networking technology in order to enhance creativity, collaboration, and communication. The development and implementation of enabling tools and methods that provide ready access to knowledge and information are among the central goals of medical informatics. Given the immensity of this challenge, the need for multi-institutional collaboration is increasingly being recognized. Collaboration has typically involved individuals who work together at the same location. With the evolution of electronic communication modalities, workers at Harvard, Columbia, McGill, and Stanford Universities jointly investigated the role that networking technologies can play in supporting research collaboration at a distance. All communications among the workers from the other three institutions were observed in order to gain insights into the limitations and successes of communications technology in supporting this distributed creative process. We analyzed the activities of the Intermed team as they sought to develop a common representation for clinical guidelines, known as the GuideLine Interchange Format (GLIF). These activities can be described as a process of computer-mediated collaborative design. We report here on the cognitive, socio-cultural, and logistical issues encountered when scientists from diverse organizations and backgrounds use communications technologies while designing and implementing shared products. Results demonstrate that the effectiveness of communication modalities is predicated on the specific objectives of the task. We identify suitable uses of email, conference calls, and face-to-face meetings. The leaders play an integral role in guiding and facilitating the group activities across modalities. Most important was the proper use of technology to support the evolution of a shared vision of group goals and methods, an element that is clearly necessary before successful collaborative designs can proceed. We interpret these research findings as they relate to the scientific collaboration via the Internet with specific focus on changes in skills required with these new media of communication.
doi:10.2196/jmir.1.suppl1.e71
PMCID: PMC1761787
Communication; Internet-based Collaboration; Cognition; Medical Education
15.  Eurocan plus report: feasibility study for coordination of national cancer research activities 
Summary
The EUROCAN+PLUS Project, called for by the European Parliament, was launched in October 2005 as a feasibility study for coordination of national cancer research activities in Europe. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people, the largest Europe–wide consultation ever conducted in the field of cancer research.
Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
It is essential to include the patients’ voice in the establishment of priority areas in cancer research at the present time. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community is evident. A top priority should be the development of translational research (in its widest form), leading to the development of effective and innovative cancer treatments and preventive strategies. Translational research ranges from bench–to–bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
The EUROCAN+PLUS Project recommends the creation of a small, permanent and independent European Cancer Initiative (ECI). This should be a model structure and was widely supported at both General Assemblies of the project. The ECI should assume responsibility for stimulating innovative cancer research and facilitating processes, becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ organizations, European institutions, Member States, industry and small and medium enterprises (SMEs), putting into practice solutions aimed at alleviating barriers to collaboration and coordination of cancer research activities in the European Union, and dealing with legal and regulatory issues. The development of an effective ECI will require time, but this entity should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co–operation between comprehensive cancer centres and basic research laboratories throughout Europe and (3) networking between funding bodies at the European level.
The European Parliament and its instruments have had a major influence in cancer control in Europe, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
Executive Summary
Cancer is one of the biggest public health crises facing Europe in the 21st century—one for which Europe is currently not prepared nor preparing itself. Cancer is a major cause of death in Europe with two million casualties and three million new cases diagnosed annually, and the situation is set to worsen as the population ages.
These facts led the European Parliament, through the Research Directorate-General of the European Commission, to call for initiatives for better coordination of cancer research efforts in the European Union. The EUROCAN+PLUS Project was launched in October 2005 as a feasibility study for coordination of national cancer research activities. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people. In this respect, the Project became the largest Europe-wide consultation ever conducted in the field of cancer research, implicating researchers, cancer centres and hospitals, administrators, healthcare professionals, funding agencies, industry, patients’ organizations and patients.
The Project first identified barriers impeding research and collaboration in research in Europe. Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain the formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
In addition, there is a shortage of leadership, a multiplicity of institutions each focusing on its own agenda, sub–optimal contact with industry, inadequate training, non–existent career paths, low personnel mobility in research especially among clinicians and inefficient funding—all conspiring against efficient collaboration in cancer care and research. European cancer research today does not have a functional translational research continuum, that is the process that exploits biomedical research innovations and converts them into prevention methods, diagnostic tools and therapies. Moreover, epidemiological research is not integrated with other types of cancer research, and the implementation of the European Directives on Clinical Trials 1 and on Personal Data Protection 2 has further slowed the innovation process in Europe. Furthermore, large inequalities in health and research exist between the EU–15 and the New Member States.
The picture is not entirely bleak, however, as the European cancer research scene presents several strengths, such as excellent basic research and clinical research and innovative etiological research that should be better exploited.
When considering recommendations, several priority dimensions had to be retained. It is essential that proposals include actions and recommendations that can benefit all Member States of the European Union and not just States with the elite centres. It is also essential to have a broader patient orientation to help provide the knowledge to establish cancer control possibilities when we exhaust what can be achieved by the implementation of current knowledge. It is vital that the actions proposed can contribute to the Lisbon Strategy to make Europe more innovative and competitive in (cancer) research.
The Project participants identified six areas for which consensus solutions should be implemented in order to obtain better coordination of cancer research activities. The required solutions are as follows. The proactive management of innovation, detection, facilitation of collaborations and maintenance of healthy competition within the European cancer research community.The establishment of an exchange portal of information for health professionals, patients and policy makers.The provision of guidance for translational and clinical research including the establishment of a translational research platform involving comprehensive cancer centres and cancer research centres.The coordination of calls and financial management of cancer research projects.The construction of a ‘one–stop shop’ as a contact interface between the industry, small and medium enterprises, scientists and other stakeholders.The support of greater involvement of healthcare professionals in translational research and multidisciplinary training.
In the course of the EUROCAN+PLUS consultative process, several key collaborative projects emerged between the various groups and institutes engaged in the consultation. There was a collaboration network established with Europe’s leading Comprehensive Cancer Centres; funding was awarded for a closer collaboration of Owners of Cancer Registries in Europe (EUROCOURSE); there was funding received from FP7 for an extensive network of leading Biological Resource Centres in Europe (BBMRI); a Working Group identified the special needs of Central, Eastern and South–eastern Europe and proposed a remedy (‘Warsaw Declaration’), and the concept of developing a one–stop shop for dealing with academia and industry including the Innovative Medicines Initiative (IMI) was discussed in detail.
Several other dimensions currently lacking were identified. There is an absolute necessity to include the patients’ voice in the establishment of priority areas in cancer research at the present time. It was a salutary lesson when it was recognized that all that is known about the quality of life of the cancer patient comes from the experience of a tiny proportion of cancer patients included in a few clinical trials. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community was evident. A top priority should be the development of translational research (in its widest form) and the development of effective and innovative cancer treatments and preventative strategies in the European Union. Translational research ranges from bench-to-bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
Having taken note of the barriers and the solutions and having examined relevant examples of existing European organizations in the field, it was agreed during the General Assembly of 19 November 2007 that the EUROCAN+PLUS Project had to recommend the creation of a small, permanent and neutral ECI. This should be a model structure and was widely supported at both General Assemblies of the project. The proposal is based on the successful model of the European Molecular Biology Organisation (EMBO), and its principal aims include providing a forum where researchers from all backgrounds and from all countries can meet with members of other specialities including patients, nurses, clinicians, funders and scientific administrators to develop priority programmes to make Europe more competitive in research and more focused on the cancer patient.
The ECI should assume responsibility for: stimulating innovative cancer research and facilitating processes;becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ and organizations;European institutions, Member States, industry and small and medium enterprises;putting into practice the aforementioned solutions aimed at alleviating barriers and coordinating cancer research activities in the EU;dealing with legal and regulatory issues.
Solutions implemented through the ECI will lead to better coordination and collaboration throughout Europe, more efficient use of resources, an increase in Europe’s attractiveness to the biomedical industry and better quality of cancer research and education of health professionals.
The Project considered that European legal instruments currently available were inadequate for addressing many aspects of the barriers identified and for the implementation of effective, lasting solutions. Therefore, the legal environment that could shelter an idea like the ECI remains to be defined but should be done so as a priority. In this context, the initiative of the European Commission for a new legal entity for research infrastructure might be a step in this direction. The development of an effective ECI will require time, but this should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass: (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co-operation between comprehensive cancer centres and basic research laboratories throughout Europe; (3) networking between funding bodies at the European level. Another topic deserving immediate attention is the creation of a European database on cancer research projects and cancer research facilities.
Despite enormous progress in cancer control in Europe during the past two decades, there was an increase of 300,000 in the number of new cases of cancer diagnosed between 2004 and 2006. The European Parliament and its instruments have had a major influence in cancer control, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
doi:10.3332/ecancer.2011.84
PMCID: PMC3234055  PMID: 22274749
16.  Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease 
Introduction
Inhibition of gamma-secretase presents a direct target for lowering Aβ production in the brain as a therapy for Alzheimer's disease (AD). However, gamma-secretase is known to process multiple substrates in addition to amyloid precursor protein (APP), most notably Notch, which has limited clinical development of inhibitors targeting this enzyme. It has been postulated that APP substrate selective inhibitors of gamma-secretase would be preferable to non-selective inhibitors from a safety perspective for AD therapy.
Methods
In vitro assays monitoring inhibitor potencies at APP γ-site cleavage (equivalent to Aβ40), and Notch ε-site cleavage, in conjunction with a single cell assay to simultaneously monitor selectivity for inhibition of Aβ production vs. Notch signaling were developed to discover APP selective gamma-secretase inhibitors. In vivo efficacy for acute reduction of brain Aβ was determined in the PDAPP transgene model of AD, as well as in wild-type FVB strain mice. In vivo selectivity was determined following seven days x twice per day (b.i.d.) treatment with 15 mg/kg/dose to 1,000 mg/kg/dose ELN475516, and monitoring brain Aβ reduction vs. Notch signaling endpoints in periphery.
Results
The APP selective gamma-secretase inhibitors ELN318463 and ELN475516 reported here behave as classic gamma-secretase inhibitors, demonstrate 75- to 120-fold selectivity for inhibiting Aβ production compared with Notch signaling in cells, and displace an active site directed inhibitor at very high concentrations only in the presence of substrate. ELN318463 demonstrated discordant efficacy for reduction of brain Aβ in the PDAPP compared with wild-type FVB, not observed with ELN475516. Improved in vivo safety of ELN475516 was demonstrated in the 7d repeat dose study in wild-type mice, where a 33% reduction of brain Aβ was observed in mice terminated three hours post last dose at the lowest dose of inhibitor tested. No overt in-life or post-mortem indications of systemic toxicity, nor RNA and histological end-points indicative of toxicity attributable to inhibition of Notch signaling were observed at any dose tested.
Conclusions
The discordant in vivo activity of ELN318463 suggests that the potency of gamma-secretase inhibitors in AD transgenic mice should be corroborated in wild-type mice. The discovery of ELN475516 demonstrates that it is possible to develop APP selective gamma-secretase inhibitors with potential for treatment for AD.
doi:10.1186/alzrt60
PMCID: PMC3031881  PMID: 21190552
17.  Quality control, analysis and secure sharing of Luminex® immunoassay data using the open source LabKey Server platform 
BMC Bioinformatics  2013;14:145.
Background
Immunoassays that employ multiplexed bead arrays produce high information content per sample. Such assays are now frequently used to evaluate humoral responses in clinical trials. Integrated software is needed for the analysis, quality control, and secure sharing of the high volume of data produced by such multiplexed assays. Software that facilitates data exchange and provides flexibility to perform customized analyses (including multiple curve fits and visualizations of assay performance over time) could increase scientists’ capacity to use these immunoassays to evaluate human clinical trials.
Results
The HIV Vaccine Trials Network and the Statistical Center for HIV/AIDS Research and Prevention collaborated with LabKey Software to enhance the open source LabKey Server platform to facilitate workflows for multiplexed bead assays. This system now supports the management, analysis, quality control, and secure sharing of data from multiplexed immunoassays that leverage Luminex xMAP® technology. These assays may be custom or kit-based. Newly added features enable labs to: (i) import run data from spreadsheets output by Bio-Plex Manager™ software; (ii) customize data processing, curve fits, and algorithms through scripts written in common languages, such as R; (iii) select script-defined calculation options through a graphical user interface; (iv) collect custom metadata for each titration, analyte, run and batch of runs; (v) calculate dose–response curves for titrations; (vi) interpolate unknown concentrations from curves for titrated standards; (vii) flag run data for exclusion from analysis; (viii) track quality control metrics across runs using Levey-Jennings plots; and (ix) automatically flag outliers based on expected values. Existing system features allow researchers to analyze, integrate, visualize, export and securely share their data, as well as to construct custom user interfaces and workflows.
Conclusions
Unlike other tools tailored for Luminex immunoassays, LabKey Server allows labs to customize their Luminex analyses using scripting while still presenting users with a single, graphical interface for processing and analyzing data. The LabKey Server system also stands out among Luminex tools for enabling smooth, secure transfer of data, quality control information, and analyses between collaborators. LabKey Server and its Luminex features are freely available as open source software at http://www.labkey.com under the Apache 2.0 license.
doi:10.1186/1471-2105-14-145
PMCID: PMC3671158  PMID: 23631706
18.  ECAT11/L1td1 Is Enriched in ESCs and Rapidly Activated During iPSCGeneration, but It Is Dispensable for the Maintenance and Induction of Pluripotency 
PLoS ONE  2011;6(5):e20461.
The principal factors that lead to proliferation and pluripotency in embryonic stem cells (ESCs) have been vigorously investigated. However, the global network of factors and their full signaling cascade is still unclear. In this study, we found that ECAT11 (L1td1) is one of the ESC-associated transcripts harboring a truncated fragment of ORF-1, a component of theL1 retrotransposable element. We generated an ECAT11 knock-in mouse by replacing its coding region with green fluorescent protein. In the early stage of development, the fluorescence was observed at the inner cell mass of blastocysts and epiblasts. Despite this specific expression, ECAT11-null mice grow normally and are fertile. In addition, ECAT11 was dispensable for both the proliferation and pluripotency of ESCs.We found rapid and robust activation of ECAT11 in fibroblasts after the forced expression of transcription factors that can give rise pluripotency in somatic cells.However, iPS cells could be established from ECAT11-null fibroblasts. Our data demonstrate thedispensability of ECAT11/L1td1 in pluripotency, despite its specific expression.
doi:10.1371/journal.pone.0020461
PMCID: PMC3102727  PMID: 21637830
19.  A Comparison of Proximity and Land Use Regression Traffic Exposure Models and Wheezing in Infants 
Environmental Health Perspectives  2006;115(2):278-284.
Background
We previously reported an association between infant wheezing and residence < 100 m from stop-and-go bus and truck traffic. The use of a proximity model, however, may lead to exposure misclassification.
Objective
Results obtained from a land use regression (LUR) model of exposure to truck and bus traffic are compared with those obtained with a proximity model. The estimates derived from the LUR model were then related to infant wheezing.
Methods
We derived a marker of diesel combustion—elemental carbon attributable to traffic sources (ECAT)—from ambient monitoring results of particulate matter with aerodynamic diameter < 2.5 μm. We developed a multiple regression model with ECAT as the outcome variable. Variables included in the model were locations of major roads, bus routes, truck traffic count, and elevation. Model parameter estimates were applied to estimate individual ECAT levels at infants’ homes.
Results
The levels of estimated ECAT at the monitoring stations ranged from 0.20 to 1.02 μg/m3. A LUR model of exposure with a coefficient of determination (R2) of 0.75 was applied to infants’ homes. The mean (± SD) ambient exposure of ECAT for infants previously categorized as unexposed, exposed to stop-and-go traffic, or exposed to moving traffic was 0.32 ± 0.06, 0.42 ± 0.14, and 0.49 ± 0.14 μg/m3, respectively. Levels of ECAT from 0.30 to 0.90 μg/m3 were significantly associated with infant wheezing.
Conclusions
The LUR model resulted in a range of ECAT individually derived for all infants’ homes that may reduce the exposure misclassification that can arise from a proximity model.
doi:10.1289/ehp.9480
PMCID: PMC1817699  PMID: 17384778
diesel; land; model; proximity; regression; spatial; traffic; use
20.  “A Good Personal Scientific Relationship”: Philip Morris Scientists and the Chulabhorn Research Institute, Bangkok 
PLoS Medicine  2008;5(12):e238.
Background
This paper examines the efforts of consultants affiliated with Philip Morris (PM), the world's leading transnational tobacco corporation, to influence scientific research and training in Thailand via the Chulabhorn Research Institute (CRI). A leading Southeast Asian institute for environmental health science, the CRI is headed by Professor Dr. Her Royal Highness Princess Chulabhorn, the daughter of the King of Thailand, and it has assumed international significance via its designation as a World Health Organization (WHO) Collaborating Centre in December 2005.
Methods and Findings
This paper analyses previously confidential tobacco industry documents that were made publicly available following litigation in the United States. PM documents reveal that ostensibly independent overseas scientists, now identified as industry consultants, were able to gain access to the Thai scientific community. Most significantly, PM scientist Roger Walk has established close connections with the CRI. Documents indicate that Walk was able to use such links to influence the study and teaching of environmental toxicology in the institute and to develop relations with key officials and local scientists so as to advance the interests of PM within Thailand and across Asia. While sensitivities surrounding royal patronage of the CRI make public criticism extremely difficult, indications of ongoing involvement by tobacco industry consultants suggest the need for detailed scrutiny of such relationships.
Conclusions
The establishment of close links with the CRI advances industry strategies to influence scientific research and debate around tobacco and health, particularly regarding secondhand smoke, to link with academic institutions, and to build relationships with national elites. Such strategies assume particular significance in the national and regional contexts presented here amid the globalisation of the tobacco pandemic. From an international perspective, particular concern is raised by the CRI's recently awarded status as a WHO Collaborating Centre. Since the network of WHO Collaborating Centres rests on the principle of “using national institutions for international purposes,” the documents presented below suggest that more rigorous safeguards are required to ensure that such use advances public health goals rather than the objectives of transnational corporations.
Jeff Collin and Ross MacKenzie analyze tobacco industry documents and find that Philip Morris consultants were able to gain access to a Thai research institute that is a WHO Collaborating Centre.
Editors' Summary
Background.
Tobacco use kills 5.4 million people a year (one person every six seconds) and accounts for one in ten adult deaths worldwide. Globally, the use of tobacco is on the rise, especially in developing countries, which have become a major target for tobacco industry marketing. The tobacco industry has worked hard to try and influence public perceptions about the risks of smoking and the risk of inhaling secondhand smoke (passive smoking). The industry has used a variety of tactics to downplay the health hazards of smoking or inhaling secondhand smoke—two examples are publishing articles casting doubts about the health hazards of tobacco and funding research that is biased toward giving pro-industry results. Another tactic is for tobacco industry consultants to try and gain entry to universities and other academic centers to see if they can influence research and teaching activities.
Why Was This Study Done?
The researchers were concerned that consultants from the tobacco company Philip Morris had gained access to an academic research center in Thailand called the Chulabhorn Research Institute (CRI). The CRI is an internationally renowned teaching institution for a variety of scientific disciplines, including environmental toxicology (the study of how chemicals in the environment, such as tobacco smoke, can affect human health), biomedicine, and biotechnology. The institute has secured funding from the Thai government, the Association of Southeast Nations and the United Nations Development Programme. In 2005 the institute's environmental toxicology unit was designated a World Health Organization (WHO) Collaborating Centre. WHO Collaborating Centres are “institutions such as research institutes, parts of universities or academies, that are designated by the Director-General of the WHO to carry out activities in support of the WHO's programs” (http://www.who.int/collaboratingcentres/en/). The researchers were concerned that Philip Morris consultants had been able to develop relationships with the CRI to help advance the company's interests.
What Did the Researchers Do and Find?
The researchers analyzed previously confidential tobacco industry documents that were made publicly available online following litigation in the United States. They searched two online collections of industry documents—the Legacy Tobacco Documents Library and Tobacco Documents Online—as well as the online collections operated by US-based tobacco companies. They found that consultants to Philip Morris were able to gain access to the scientific community in Thailand. A Philip Morris scientist named Roger Walk was able to establish close connections to the CRI, and he used these connections to influence research and teaching activities at the CRI on environmental toxicology. Walk was also able to build relationships with government officials and scientists in Thailand to help advance the interests of Philip Morris in the country and across Asia.
What Do these Findings Mean?
This study provides evidence that the tobacco industry has established close links with a research institute in Thailand that collaborates with the WHO, and has been able to influence the institute's teaching curriculum and research. Such links are of great concern to the public health community, which is working hard to reduce deaths and disease due to tobacco. These links raise the possibility that the tobacco industry is managing to influence medical research and teaching at academic institutions. The WHO has stated that a firewall is in place between itself and the tobacco industry—but the study authors argue, based on their findings, that “this firewall is not impenetrable.” The study findings, they conclude, highlight a challenge posed to international tobacco control efforts, especially with respect to Article 5.3 of an international treaty called the WHO Framework Convention on Tobacco Control; Article 5.3 addresses the need to protect public health policies from the vested interests of the tobacco industry. The authors say that better safeguards must be put in place to prevent tobacco companies from thwarting public health goals.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050238.
The Legacy Tobacco Documents Library contains over 9.7 million documents created by tobacco companies
Tobacco Documents Online contains over 4 million tobacco industry documents
Over 900 WHO Collaborating Centres are at work in 99 Member States on many health disciplines
The WHO held an inquiry in 2000 into possible tobacco industry influence over the organization (and over other UN agencies), and has published its recommendations in response to this inquiry
The WHO Framework Convention on Tobacco Control is an international treaty on controlling tobacco
doi:10.1371/journal.pmed.0050238
PMCID: PMC2605886  PMID: 19108600
21.  ProteinTracker: an application for managing protein production and purification 
BMC Research Notes  2012;5:224.
Background
Laboratories that produce protein reagents for research and development face the challenge of deciding whether to track batch-related data using simple file based storage mechanisms (e.g. spreadsheets and notebooks), or commit the time and effort to install, configure and maintain a more complex laboratory information management system (LIMS). Managing reagent data stored in files is challenging because files are often copied, moved, and reformatted. Furthermore, there is no simple way to query the data if/when questions arise. Commercial LIMS often include additional modules that may be paid for but not actually used, and often require software expertise to truly customize them for a given environment.
Findings
This web-application allows small to medium-sized protein production groups to track data related to plasmid DNA, conditioned media samples (supes), cell lines used for expression, and purified protein information, including method of purification and quality control results. In addition, a request system was added that includes a means of prioritizing requests to help manage the high demand of protein production resources at most organizations. ProteinTracker makes extensive use of existing open-source libraries and is designed to track essential data related to the production and purification of proteins.
Conclusions
ProteinTracker is an open-source web-based application that provides organizations with the ability to track key data involved in the production and purification of proteins and may be modified to meet the specific needs of an organization. The source code and database setup script can be downloaded from http://sourceforge.net/projects/proteintracker. This site also contains installation instructions and a user guide. A demonstration version of the application can be viewed at http://www.proteintracker.org.
doi:10.1186/1756-0500-5-224
PMCID: PMC3436699  PMID: 22574679
Protein; Production; Purification; Reagent; Tracking; Prioritization; Web; Application
22.  The Collaboratory for MS3D: A New Cyberinfrastructure for the Structural Elucidation of Biological Macromolecules and their Assemblies Using Mass Spectrometry-based Approaches 
Journal of proteome research  2008;7(11):4848-4857.
Modern biomedical research is evolving with the rapid growth of diverse data types, biophysical characterization methods, computational tools and extensive collaboration among researchers spanning various communities and having complementary backgrounds and expertise. Collaborating researchers are increasingly dependent on shared data and tools made available by other investigators with common interests, thus forming communities that transcend the traditional boundaries of the single research lab or institution. Barriers, however, remain to the formation of these virtual communities, usually due to the steep learning curve associated with becoming familiar with new tools, or with the difficulties associated with transferring data between tools. Recognizing the need for shared reference data and analysis tools, we are developing an integrated knowledge environment that supports productive interactions among researchers. Here we report on our current collaborative environment, which focuses on bringing together structural biologists working in the area of mass spectrometric based methods for the analysis of tertiary and quaternary macromolecular structures (MS3D) called the Collaboratory for MS3D (C-MS3D). C-MS3D is a web-portal designed to provide collaborators with a shared work environment that integrates data storage and management with data analysis tools. Files are stored and archived along with pertinent meta data in such a way as to allow file handling to be tracked (data provenance) and data files to be searched using keywords and modification dates. While at this time the portal is designed around a specific application, the shared work environment is a general approach to building collaborative work groups. The goal of which is to not only provide a common data sharing and archiving system but also to assist in the building of new collaborations and to spur the development of new tools and technologies.
doi:10.1021/pr800443f
PMCID: PMC2677910  PMID: 18817429
Collaboratory; data analysis tools; structural biology; mass spectrometry
23.  iLAP: a workflow-driven software for experimental protocol development, data acquisition and analysis 
BMC Bioinformatics  2009;10:390.
Background
In recent years, the genome biology community has expended considerable effort to confront the challenges of managing heterogeneous data in a structured and organized way and developed laboratory information management systems (LIMS) for both raw and processed data. On the other hand, electronic notebooks were developed to record and manage scientific data, and facilitate data-sharing. Software which enables both, management of large datasets and digital recording of laboratory procedures would serve a real need in laboratories using medium and high-throughput techniques.
Results
We have developed iLAP (Laboratory data management, Analysis, and Protocol development), a workflow-driven information management system specifically designed to create and manage experimental protocols, and to analyze and share laboratory data. The system combines experimental protocol development, wizard-based data acquisition, and high-throughput data analysis into a single, integrated system. We demonstrate the power and the flexibility of the platform using a microscopy case study based on a combinatorial multiple fluorescence in situ hybridization (m-FISH) protocol and 3D-image reconstruction. iLAP is freely available under the open source license AGPL from http://genome.tugraz.at/iLAP/.
Conclusion
iLAP is a flexible and versatile information management system, which has the potential to close the gap between electronic notebooks and LIMS and can therefore be of great value for a broad scientific community.
doi:10.1186/1471-2105-10-390
PMCID: PMC2789074  PMID: 19941647
24.  Traffic-Related Air Pollution Exposure in the First Year of Life and Behavioral Scores at 7 Years of Age 
Environmental Health Perspectives  2013;121(6):731-736.
Background: There is increasing concern about the potential effects of traffic-related air pollution (TRAP) on the developing brain. The impact of TRAP exposure on childhood behavior is not fully understood because of limited epidemiologic studies.
Objective: We explored the association between early-life exposure to TRAP using a surrogate, elemental carbon attributed to traffic (ECAT), and attention deficit/hyperactivity disorder (ADHD) symptoms at 7 years of age.
Methods: From the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort we collected data on exposure to ECAT during infancy and behavioral scores at 7 years of age. Children enrolled in CCAAPS had at least one atopic parent and a birth residence either < 400 m or > 1,500 m from a major highway. Children were followed from infancy through 7 years of age. ECAT exposure during the first year of life was estimated based on measurements from 27 air sampling sites and land use regression modeling. Parents completed the Behavioral Assessment System for Children, 2nd Edition, when the child was 7 years of age. ADHD-related symptoms were assessed using the Hyperactivity, Attention Problems, Aggression, Conduct Problems, and Atypicality subscales.
Results: Exposure to the highest tertile of ECAT during the child’s first year of life was significantly associated with Hyperactivity T-scores in the “at risk” range at 7 years of age, after adjustment [adjusted odds ratio (aOR) = 1.7; 95% CI: 1.0, 2.7]. Stratification by maternal education revealed a stronger association in children whose mothers had higher education (aOR = 2.3; 95% CI: 1.3, 4.1).
Conclusions: ECAT exposure during infancy was associated with higher Hyperactivity scores in children; this association was limited to children whose mothers had more than a high school education.
doi:10.1289/ehp.1205555
PMCID: PMC3672910  PMID: 23694812
attention deficit/hyperactivity disorder; child behavior; epidemiology; land use regression; traffic-related air pollution
25.  Internet Image Viewer (iiV) 
BMC Medical Imaging  2008;8:10.
Background
Visualizing 3-dimensional (3-D) datasets is an important part of modern neuroimaging research. Many tools address this problem; however, they often fail to address specific needs and flexibility, such as the ability to work with different data formats, to control how and what data are displayed, to interact with values, and to undo mistakes.
Results
iiV, an interactive software program for displaying 3-D brain images, is described. This tool was programmed to solve basic problems in 3-D data visualization. It is written in Java so it is extensible, is platform independent, and can display images within web pages.
iiV displays 3-D images as 2-dimensional (2-D) slices with each slice being an independent object with independent features such as location, zoom, colors, labels, etc. Feature manipulation becomes easier by having a full set of editing capabilities including the following: undo or redo changes; drag, copy, delete and paste objects; and save objects with their features to a file for future editing. It can read multiple standard positron emission tomography (PET) and magnetic resonance imaging (MRI) file formats like ECAT, ECAT7, ANALYZE, NIfTI-1 and DICOM. We present sample applications to illustrate some of the features and capabilities.
Conclusion
iiV is an image display tool with many useful features. It is highly extensible, platform independent, and web-compatible. This report summarizes its features and applications, while illustrating iiV's usefulness to the biomedical imaging community.
doi:10.1186/1471-2342-8-10
PMCID: PMC2430954  PMID: 18510765

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