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1.  Science and policy on endocrine disrupters must not be mixed: a reply to a “common sense” intervention by toxicology journal editors 
Environmental Health  2013;12:69.
The “common sense” intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
doi:10.1186/1476-069X-12-69
PMCID: PMC3765603  PMID: 23981490
Endocrine disrupting chemicals; Environment; Health; Precautionary principle; Regulatory toxicology
2.  An editor for pathway drawing and data visualization in the Biopathways Workbench 
BMC Systems Biology  2009;3:99.
Background
Pathway models serve as the basis for much of systems biology. They are often built using programs designed for the purpose. Constructing new models generally requires simultaneous access to experimental data of diverse types, to databases of well-characterized biological compounds and molecular intermediates, and to reference model pathways. However, few if any software applications provide all such capabilities within a single user interface.
Results
The Pathway Editor is a program written in the Java programming language that allows de-novo pathway creation and downloading of LIPID MAPS (Lipid Metabolites and Pathways Strategy) and KEGG lipid metabolic pathways, and of measured time-dependent changes to lipid components of metabolism. Accessed through Java Web Start, the program downloads pathways from the LIPID MAPS Pathway database (Pathway) as well as from the LIPID MAPS web server . Data arises from metabolomic (lipidomic), microarray, and protein array experiments performed by the LIPID MAPS consortium of laboratories and is arranged by experiment. Facility is provided to create, connect, and annotate nodes and processes on a drawing panel with reference to database objects and time course data. Node and interaction layout as well as data display may be configured in pathway diagrams as desired. Users may extend diagrams, and may also read and write data and non-lipidomic KEGG pathways to and from files. Pathway diagrams in XML format, containing database identifiers referencing specific compounds and experiments, can be saved to a local file for subsequent use. The program is built upon a library of classes, referred to as the Biopathways Workbench, that convert between different file formats and database objects. An example of this feature is provided in the form of read/construct/write access to models in SBML (Systems Biology Markup Language) contained in the local file system.
Conclusion
Inclusion of access to multiple experimental data types and of pathway diagrams within a single interface, automatic updating through connectivity to an online database, and a focus on annotation, including reference to standardized lipid nomenclature as well as common lipid names, supports the view that the Pathway Editor represents a significant, practicable contribution to current pathway modeling tools.
doi:10.1186/1752-0509-3-99
PMCID: PMC2763869  PMID: 19799790
3.  Skyline: an open source document editor for creating and analyzing targeted proteomics experiments 
Bioinformatics  2010;26(7):966-968.
Summary: Skyline is a Windows client application for targeted proteomics method creation and quantitative data analysis. It is open source and freely available for academic and commercial use. The Skyline user interface simplifies the development of mass spectrometer methods and the analysis of data from targeted proteomics experiments performed using selected reaction monitoring (SRM). Skyline supports using and creating MS/MS spectral libraries from a wide variety of sources to choose SRM filters and verify results based on previously observed ion trap data. Skyline exports transition lists to and imports the native output files from Agilent, Applied Biosystems, Thermo Fisher Scientific and Waters triple quadrupole instruments, seamlessly connecting mass spectrometer output back to the experimental design document. The fast and compact Skyline file format is easily shared, even for experiments requiring many sample injections. A rich array of graphs displays results and provides powerful tools for inspecting data integrity as data are acquired, helping instrument operators to identify problems early. The Skyline dynamic report designer exports tabular data from the Skyline document model for in-depth analysis with common statistical tools.
Availability: Single-click, self-updating web installation is available at http://proteome.gs.washington.edu/software/skyline. This web site also provides access to instructional videos, a support board, an issues list and a link to the source code project.
Contact: brendanx@u.washington.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
doi:10.1093/bioinformatics/btq054
PMCID: PMC2844992  PMID: 20147306
4.  PREP-Mt: predictive RNA editor for plant mitochondrial genes 
BMC Bioinformatics  2005;6:96.
Background
In plants, RNA editing is a process that converts specific cytidines to uridines and uridines to cytidines in transcripts from virtually all mitochondrial protein-coding genes. There are thousands of plant mitochondrial genes in the sequence databases, but sites of RNA editing have not been determined for most. Accurate methods of RNA editing site prediction will be important in filling in this information gap and could reduce or even eliminate the need for experimental determination of editing sites for many sequences. Because RNA editing tends to increase protein conservation across species by "correcting" codons that specify unconserved amino acids, this principle can be used to predict editing sites by identifying positions where an RNA editing event would increase the conservation of a protein to homologues from other plants. PREP-Mt takes this approach to predict editing sites for any protein-coding gene in plant mitochondria.
Results
To test the general applicability of the PREP-Mt methodology, RNA editing sites were predicted for 370 full-length or nearly full-length DNA sequences and then compared to the known sites of RNA editing for these sequences. Of 60,263 cytidines in this test set, PREP-Mt correctly classified 58,994 as either an edited or unedited site (accuracy = 97.9%). PREP-Mt properly identified 3,038 of the 3,698 known sites of RNA editing (sensitivity = 82.2%) and 55,956 of the 56,565 known unedited sites (specificity = 98.9%). Accuracy and sensitivity increased to 98.7% and 94.7%, respectively, after excluding the 489 silent editing sites (which have no effect on protein sequence or function) from the test set.
Conclusion
These results indicate that PREP-Mt is effective at identifying C to U RNA editing sites in plant mitochondrial protein-coding genes. Thus, PREP-Mt should be useful in predicting protein sequences for use in molecular, biochemical, and phylogenetic analyses. In addition, PREP-Mt could be used to determine functionality of a mitochondrial gene or to identify particular sequences with unusual editing properties. The PREP-Mt methodology should be applicable to any system where RNA editing increases protein conservation across species.
doi:10.1186/1471-2105-6-96
PMCID: PMC1087475  PMID: 15826309
5.  Representation of authors and editors from countries with different human development indexes in the leading literature on tropical medicine: survey of current evidence 
BMJ : British Medical Journal  2004;328(7450):1229-1232.
Objective To assess the current international representation of members of editorial and advisory boards and authors in the leading peer reviewed literature on tropical medicine.
Design Systematic review.
Main outcome measures Country affiliations, as classified by the human development index, of editorial and advisory board members of all tropical medicine journals referenced by the Institute of Scientific Information (ISI) as of late 2003 and of all contributing authors of full articles published in the six leading journals on tropical medicine in 2000-2.
Results Sixteen (5.1%) of the 315 editorial and advisory board members from the 12 ISI referenced journals on tropical medicine are affiliated to countries with a low human development index and 223 (70.8%) to countries with a high index. Examination of the 2384 full articles published in 2000-2 in the six highest ranking tropical medicine journals showed that 48.1% of contributing authors are affiliated to countries with a high human development index, whereas the percentage of authors from countries with a low index was 13.7%. Articles written exclusively by authors from low ranked countries accounted for 5.0%. Our data indicate that research collaborations between a country with a high human development index and one that has either a medium or a low index are common and account for 26.5% and 16.1% of all full articles, respectively.
Conclusion Current collaborations should be transformed into research partnerships, with the goals of mutual learning and institutional capacity strengthening in the developing world.
doi:10.1136/bmj.38069.518137.F6
PMCID: PMC416596  PMID: 15059851
6.  A Diagram Editor for Efficient Biomedical Knowledge Capture and Integration 
Understanding the molecular mechanisms underlying complex disorders requires the integration of data and knowledge from different sources including free text literature and various biomedical databases. To facilitate this process, we created the Biomedical Concept Diagram Editor (BCDE) to help researchers distill knowledge from data and literature and aid the process of hypothesis development. A key feature of BCDE is the ability to capture information with a simple drag-and-drop. This is a vast improvement over manual methods of knowledge and data recording and greatly increases the efficiency of the biomedical researcher. BCDE also provides a unique concept matching function to enforce consistent terminology, which enables conceptual relationships deposited by different researchers in the BCDE database to be mined and integrated for intelligible and useful results. We hope BCDE will promote the sharing and integration of knowledge from different researchers for effective hypothesis development.
PMCID: PMC3041526  PMID: 21347131
7.  Authors, editors, and the signs, symptoms and causes of plagiarism 
Saudi Journal of Anaesthesia  2011;5(3):303-307.
Plagiarism and inadequate citing appear to have reached epidemic proportions in research publication. This article discusses how plagiarism is defined and suggests some possible causes for the increase in the plagiarism disease. Most editors do not have much tolerance for text re-use with inadequate citation regardless of reasons why words are copied from other sources without correct attribution. However, there is now some awareness that re-use of words in research articles to improve the writing or “the English” (which has become a common practice) should be distinguished from intentional deceit for the purpose of stealing other authors’ ideas (which appears to remain a very rare practice). Although it has become almost as easy for editors to detect duplicate text as it is for authors to re-use text from other sources, editors often fail to consider the reasons why researchers resort to this strategy, and tend to consider any text duplication as a symptom of serious misconduct. As a result, some authors may be stigmatized unfairly by being labeled as plagiarists. The article concludes with practical advice for researchers on how to improve their writing and citing skills and thus avoid accusations of plagiarism.
doi:10.4103/1658-354X.84107
PMCID: PMC3168350  PMID: 21957412
Plagiarism; editors; authors
8.  Avogadro: an advanced semantic chemical editor, visualization, and analysis platform 
Background
The Avogadro project has developed an advanced molecule editor and visualizer designed for cross-platform use in computational chemistry, molecular modeling, bioinformatics, materials science, and related areas. It offers flexible, high quality rendering, and a powerful plugin architecture. Typical uses include building molecular structures, formatting input files, and analyzing output of a wide variety of computational chemistry packages. By using the CML file format as its native document type, Avogadro seeks to enhance the semantic accessibility of chemical data types.
Results
The work presented here details the Avogadro library, which is a framework providing a code library and application programming interface (API) with three-dimensional visualization capabilities; and has direct applications to research and education in the fields of chemistry, physics, materials science, and biology. The Avogadro application provides a rich graphical interface using dynamically loaded plugins through the library itself. The application and library can each be extended by implementing a plugin module in C++ or Python to explore different visualization techniques, build/manipulate molecular structures, and interact with other programs. We describe some example extensions, one which uses a genetic algorithm to find stable crystal structures, and one which interfaces with the PackMol program to create packed, solvated structures for molecular dynamics simulations. The 1.0 release series of Avogadro is the main focus of the results discussed here.
Conclusions
Avogadro offers a semantic chemical builder and platform for visualization and analysis. For users, it offers an easy-to-use builder, integrated support for downloading from common databases such as PubChem and the Protein Data Bank, extracting chemical data from a wide variety of formats, including computational chemistry output, and native, semantic support for the CML file format. For developers, it can be easily extended via a powerful plugin mechanism to support new features in organic chemistry, inorganic complexes, drug design, materials, biomolecules, and simulations. Avogadro is freely available under an open-source license from http://avogadro.openmolecules.net.
doi:10.1186/1758-2946-4-17
PMCID: PMC3542060  PMID: 22889332
9.  Photoletter to the editor: Dermoscopy for discriminating between pityriasis rubra pilaris and psoriasis 
Pityriasis rubra pilaris (PRP) is a relatively uncommon entity that often has to be clinically differentiated from other erythematosquamous skin diseases, such as psoriasis. Dermoscopy has already been shown to enhance clinical evaluation of inflammatory skin conditions and dermoscopic patterns of various diseases, including psoriasis, have been documented. In the current manuscript we present the dermoscopic findings observed in two patients suffering from PRP and psoriasis, respectively. The dermoscopic pattern of PRP consisted of round/oval yellowish areas surrounded by vessels of mixed morphology. The latter findings are clearly distinct from the dermoscopic features of psoriasis, which have been extensively investigated previously and are presented also in the psoriatic patient herein. This observation represents an initial indication that dermoscopy could be of value in differentiating between the two entities.
doi:10.3315/jdcr.2013.1131
PMCID: PMC3622511  PMID: 23580911
blood vessels; dermatoscopy; dermoscopy; pityriasis rubra pilaris; psoriasis
10.  “Hardly worth the effort”? Medical journals’ policies and their editors’ and publishers’ views on trial registration and publication bias: quantitative and qualitative study 
Objectives To determine the proportion of medical journals requiring trial registration and to understand their reasons for adopting (or not adopting) such policies and other measures designed to reduce publication bias.
Design Quantitative study of journals’ instructions to authors (in June 2012) and qualitative study of editors’ and publishers’ views on trial registration and publication bias (carried out in Autumn 2012).
Setting Random selection of 200 medical journals publishing clinical trials identified from the Cochrane CENTRAL database.
Participants Editors (n=13) and publishers (n=3) of journals with different policies on trial registration (and with recently changed policies) identified from the survey of their instructions to authors.
Results Only 55/200 journals (28%) required trial registration according to their instructions and a further three (2%) encouraged it. The editors and publishers interviewed explained their journals’ reluctance to require registration in terms of not wanting to lose out to rival journals, not wanting to reject otherwise sound articles or submissions from developing countries, and perceptions that such policies were not relevant to all journals. Some interviewees considered that registration was unnecessary for small or exploratory studies.
Conclusions Although many major medical journals state that they will only publish clinical trials that have been prospectively registered, and such policies have been associated with a dramatic increase in the number of trials being registered, most smaller journals have not adopted such policies. Editors and publishers may be reluctant to require registration because they do not understand its benefits or because they fear that adopting such a policy would put their journal at a disadvantage to competitors.
doi:10.1136/bmj.f5248
PMCID: PMC3805489  PMID: 24014339
11.  Evaluating adherence to the International Committee of Medical Journal Editors’ policy of mandatory, timely clinical trial registration 
Objective
To determine whether two specific criteria in Uniform Requirements for Manuscripts (URM) created by the International Committee of Medical Journal Editors (ICMJE)—namely, including the trial ID registration within manuscripts and timely registration of trials, are being followed.
Materials and methods
Observational study using computerized analysis of publicly available Medline article data and clinical trial registry data. We analyzed a purposive set of five ICMJE founding journals looking at all trial articles published in those journals during 2010–2011, and data from the ClinicalTrials.gov (CTG) trial registry. We measured adherence to trial ID inclusion policy as the percentage of trial journal articles that contained a valid trial ID within the article (journal-based sample). Adherence to timely registration was measured as the percentage of trials that registered the trial before enrolling the first participant within a 60-day grace period. We also examined timely registration rates by year of all phase II and higher interventional trials in CTG (registry-based sample).
Results
To determine trial ID inclusion, we analyzed 698 clinical trial articles in five journals. A total of 95.8% (661/690) of trial journal articles included the trial ID. In 88.3% the trial-article link is stored within a structured Medline field. To evaluate timely registration, we analyzed trials referenced by 451 articles from the selected five journals. A total of 60% (272/451) of articles were registered in a timely manner with an improving trend for trials initiated in later years (eg, 89% of trials that began in 2008 were registered in a timely manner). In the registry-based sample, the timely registration rates ranged from 56% for trials registered in 2006 to 72% for trials registered in 2011.
Discussion
Adherence to URM requirements for registration and trial ID inclusion increases the utility of PubMed and links it in an important way to clinical trial repositories. This new integrated knowledge source can facilitate research prioritization, clinical guidelines creation, and precision medicine.
Conclusions
The five selected journals adhere well to the policy of mandatory trial registration and also outperform the registry in adherence to timely registration. ICMJE's URM policy represents a unique international mandate that may be providing a powerful incentive for sponsors and investigators to document clinical trials and trial result publications and thus fulfill important obligations to trial participants and society.
doi:10.1136/amiajnl-2012-001501
PMCID: PMC3715364  PMID: 23396544
clinical trials as topic/legislation; registries; cross-sectional analysis; Databases; publication policy; trial registration
12.  FORG3D: Force-directed 3D graph editor for visualization of integrated genome scale data 
BMC Systems Biology  2009;3:26.
Background
Genomics research produces vast amounts of experimental data that needs to be integrated in order to understand, model, and interpret the underlying biological phenomena. Interpreting these large and complex data sets is challenging and different visualization methods are needed to help produce knowledge from the data.
Results
To help researchers to visualize and interpret integrated genomics data, we present a novel visualization method and bioinformatics software tool called FORG3D that is based on real-time three-dimensional force-directed graphs. FORG3D can be used to visualize integrated networks of genome scale data such as interactions between genes or gene products, signaling transduction, metabolic pathways, functional interactions and evolutionary relationships. Furthermore, we demonstrate its utility by exploring gene network relationships using integrated data sets from a Caenorhabditis elegans Parkinson's disease model.
Conclusion
We have created an open source software tool called FORG3D that can be used for visualizing and exploring integrated genome scale data.
doi:10.1186/1752-0509-3-26
PMCID: PMC2651117  PMID: 19239683
13.  Jalview Version 2—a multiple sequence alignment editor and analysis workbench 
Bioinformatics  2009;25(9):1189-1191.
Summary: Jalview Version 2 is a system for interactive WYSIWYG editing, analysis and annotation of multiple sequence alignments. Core features include keyboard and mouse-based editing, multiple views and alignment overviews, and linked structure display with Jmol. Jalview 2 is available in two forms: a lightweight Java applet for use in web applications, and a powerful desktop application that employs web services for sequence alignment, secondary structure prediction and the retrieval of alignments, sequences, annotation and structures from public databases and any DAS 1.53 compliant sequence or annotation server.
Availability: The Jalview 2 Desktop application and JalviewLite applet are made freely available under the GPL, and can be downloaded from www.jalview.org
Contact: g.j.barton@dundee.ac.uk
doi:10.1093/bioinformatics/btp033
PMCID: PMC2672624  PMID: 19151095
14.  Do Author-Suggested Reviewers Rate Submissions More Favorably than Editor-Suggested Reviewers? A Study on Atmospheric Chemistry and Physics 
PLoS ONE  2010;5(10):e13345.
Background
Ratings in journal peer review can be affected by sources of bias. The bias variable investigated here was the information on whether authors had suggested a possible reviewer for their manuscript, and whether the editor had taken up that suggestion or had chosen a reviewer that had not been suggested by the authors. Studies have shown that author-suggested reviewers rate manuscripts more favorably than editor-suggested reviewers do.
Methodology/Principal Findings
Reviewers' ratings on three evaluation criteria and the reviewers' final publication recommendations were available for 552 manuscripts (in total 1145 reviews) that were submitted to Atmospheric Chemistry and Physics, an interactive open access journal using public peer review (authors' and reviewers' comments are publicly exchanged). Public peer review is supposed to bring a new openness to the reviewing process that will enhance its objectivity. In the statistical analysis the quality of a manuscript was controlled for to prevent favorable reviewers' ratings from being attributable to quality instead of to the bias variable.
Conclusions/Significance
Our results agree with those from other studies that editor-suggested reviewers rated manuscripts between 30% and 42% less favorably than author-suggested reviewers. Against this backdrop journal editors should consider either doing without the use of author-suggested reviewers or, if they are used, bringing in more than one editor-suggested reviewer for the review process (so that the review by author-suggested reviewers can be put in perspective).
doi:10.1371/journal.pone.0013345
PMCID: PMC2954795  PMID: 20976226
15.  Guidelines, Editors, Pharma And The Biological Paradigm Shift 
Mens Sana Monographs  2007;5(1):27-30.
Private investment in biomedical research has increased over the last few decades. At most places it has been welcomed as the next best thing to technology itself. Much of the intellectual talent from academic institutions is getting absorbed in lucrative positions in industry. Applied research finds willing collaborators in venture capital funded industry, so a symbiotic growth is ensured for both.
There are significant costs involved too. As academia interacts with industry, major areas of conflict of interest especially applicable to biomedical research have arisen. They are related to disputes over patents and royalty, hostile encounters between academia and industry, as also between public and private enterprise, legal tangles, research misconduct of various types, antagonistic press and patient-advocate lobbies and a general atmosphere in which commercial interest get precedence over patient welfare.
Pharma image stinks because of a number of errors of omission and commission. A recent example is suppression of negative findings about Bayer's Trasylol (Aprotinin) and the marketing maneuvers of Eli Lilly's Xigris (rhAPC). Whenever there is a conflict between patient vulnerability and profit motives, pharma often tends to tilt towards the latter. Moreover there are documents that bring to light how companies frequently cross the line between patient welfare and profit seeking behaviour.
A voluntary moratorium over pharma spending to pamper drug prescribers is necessary. A code of conduct adopted recently by OPPI in India to limit pharma company expenses over junkets and trinkets is a welcome step.
Clinical practice guidelines (CPG) are considered important as they guide the diagnostic/therapeutic regimen of a large number of medical professionals and hospitals and provide recommendations on drugs, their dosages and criteria for selection. Along with clinical trials, they are another area of growing influence by the pharmaceutical industry. For example, in a relatively recent survey of 2002, it was found that about 60% of 192 authors of clinical practice guidelines reported they had financial connections with the companies whose drugs were under consideration. There is a strong case for making CPGs based not just on effectivity but cost effectivity. The various ramifications of this need to be spelt out. Work of bodies like the Appraisal of Guidelines Research and Evaluation (AGREE) Collaboration and Guidelines Advisory Committee (GAC) are also worth a close look.
Even the actions of Foundations that work for disease amelioration have come under scrutiny. The process of setting up ‘Best Practices’ Guidelines for interactions between the pharmaceutical industry and clinicians has already begun and can have important consequences for patient care. Similarly, Good Publication Practice (GPP) for pharmaceutical companies have also been set up aimed at improving the behaviour of drug companies while reporting drug trials
The rapidly increasing trend toward influence and control by industry has become a concern for many. It is of such importance that the Association of American Medical Colleges has issued two relatively new documents - one, in 2001, on how to deal with individual conflicts of interest; and the other, in 2002, on how to deal with institutional conflicts of interest in the conduct of clinical research. Academic Medical Centers (AMCs), as also medical education and research institutions at other places, have to adopt means that minimize their conflicts of interest.
Both medical associations and research journal editors are getting concerned with individual and institutional conflicts of interest in the conduct of clinical research and documents are now available which address these issues. The 2001 ICMJE revision calls for full disclosure of the sponsor's role in research, as well as assurance that the investigators are independent of the sponsor, are fully accountable for the design and conduct of the trial, have independent access to all trial data and control all editorial and publication decisions. However the findings of a 2002 study suggest that academic institutions routinely participate in clinical research that does not adhere to ICMJE standards of accountability, access to data and control of publication.
There is an inevitable slant to produce not necessarily useful but marketable products which ensure the profitability of industry and research grants outflow to academia. Industry supports new, not traditional, therapies, irrespective of what is effective. Whatever traditional therapy is supported is most probably because the company concerned has a product with a big stake there, which has remained a ‘gold standard’ or which that player thinks has still some ‘juice’ left.
Industry sponsorship is mainly for potential medications, not for trying to determine whether there may be non-pharmacological interventions that may be equally good, if not better. In the paradigm shift towards biological psychiatry, the role of industry sponsorship is not overt but probably more pervasive than many have realised, or the right thinking may consider good, for the health of the branch in the long run.
An issue of major concern is protection of the interests of research subjects. Patients agree to become research subjects not only for personal medical benefit but, as an extension, to benefit the rest of the patient population and also advance medical research.
We all accept that industry profits have to be made, and investment in research and development by the pharma industry is massive. However, we must also accept there is a fundamental difference between marketing strategies for other entities and those for drugs.
The ultimate barometer is patient welfare and no drug that compromises it can stand the test of time. So, how does it make even commercial sense in the long term to market substandard products? The greatest mistake long-term players in industry may make is try to adopt the shady techniques of the upstart new entrant. Secrecy of marketing/sales tactics, of the process of manufacture, of other strategies and plans of business expansion, of strategies to tackle competition are fine business tactics. But it is critical that secrecy as a tactic not extend to reporting of research findings, especially those contrary to one's product.
Pharma has no option but to make a quality product, do comprehensive adverse reaction profiles, and market it only if it passes both tests.
Why does pharma adopt questionable tactics? The reasons are essentially two:
What with all the constraints, a drug comes to the pharmacy after huge investments. There are crippling overheads and infrastructure costs to be recovered. And there are massive profit margins to be maintained. If these were to be dependent only on genuine drug discoveries, that would be taking too great a risk.Industry players have to strike the right balance between profit making and credibility. In profit making, the marketing champions play their role. In credibility ratings, researchers and paid spokes-persons play their role. All is hunky dory till marketing is based on credibility. When there is nothing available to make for credibility, something is projected as one and marketing carried out, in the calculated hope that profits can accrue, since profit making must continue endlessly. That is what makes pharma adopt even questionable means to make profits.
Essentially, there are four types of drugs. First, drugs that work and have minimal side-effects; second, drugs which work but have serious side-effects; third, drugs that do not work and have minimal side-effects; and fourth, drugs which work minimally but have serious side-effects. It is the second and fourth types that create major hassles for industry. Often, industry may try to project the fourth type as the second to escape censure.
The major cat and mouse game being played by conscientious researchers is in exposing the third and fourth for what they are and not allowing industry to palm them off as the first and second type respectively. The other major game is in preventing the second type from being projected as the first. The third type are essentially harmless, so they attract censure all right and some merriment at the antics to market them. But they escape anything more than a light rap on the knuckles, except when they are projected as the first type.
What is necessary for industry captains and long-term players is to realise:
Their major propelling force can only be producing the first type. 2. They accept the second type only till they can lay their hands on the first. 3. The third type can be occasionally played around with to shore up profits, but never by projecting them as the first type. 4. The fourth type are the laggards, real threat to credibility and therefore do not deserve any market hype or promotion.
In finding out why most pharma indulges in questionable tactics, we are lead to some interesting solutions to prevent such tactics with the least amount of hassles for all concerned, even as both profits and credibility are kept intact.
doi:10.4103/0973-1229.32176
PMCID: PMC3192391  PMID: 22058616
Academia; Pharmaceutical Industry; Clinical Practice Guidelines; Best Practice Guidelines; Academic Medical Centers; Medical Associations; Research Journals; Clinical Research; Public Welfare; Pharma Image; Corporate Welfare; Biological Psychiatry; Law Suits Against Industry
16.  The publication of ethically uncertain research: attitudes and practices of journal editors 
BMC Medical Ethics  2012;13:4.
Background
Publication of ethically uncertain research occurs despite well-published guidelines set forth in documents such as the Declaration of Helsinki. Such guidelines exist to aide editorial staff in making decisions regarding ethical acceptability of manuscripts submitted for publication, yet examples of ethically suspect and uncertain publication exist. Our objective was to survey journal editors regarding practices and attitudes surrounding such dilemmas.
Methods
The Editor-in-chief of each of the 103 English-language journals from the 2005 Abridged Index Medicus list publishing original research were asked to complete a survey sent to them by email between September-December 2007.
Results
A response rate of 33% (n = 34) was obtained from the survey. 18% (n = 6) of respondents had published ethically uncertain or suspect research within the last 10 years. 85% (n = 29) of respondents stated they would always reject ethically uncertain articles submitted for publication on ethical grounds alone. 12% (n = 4) of respondents stated they would approach each submission on a case-by-case basis. 3% (n = 1) stated they would be likely to publish such research, but only with accompanying editorial. Only 38% (n = 13) give reviewers explicit instruction to reject submissions on ethical grounds if found wanting.
Conclusions
Editorial compliance with the Declaration of Helsinki in rejecting research that is conducted unethically was difficult to ascertain because of a poor response rate despite multiple attempts using different modalities. Of those who did respond, the majority do reject ethically suspect research but few explicitly advise reviewers to do so. In this study editors did not take advantage of the opportunity to describe their support for the rejection of the publication of unethical research.
doi:10.1186/1472-6939-13-4
PMCID: PMC3378458  PMID: 22494972
Editors; Ethics; Publication ethics
17.  Can a core outcome set improve the quality of systematic reviews? – a survey of the Co-ordinating Editors of Cochrane review groups 
Trials  2013;14:21.
Background
Missing outcome data or the inconsistent reporting of outcome data in clinical research can affect the quality of evidence within a systematic review. A potential solution is an agreed standardized set of outcomes known as a core outcome set (COS) to be measured in all studies for a specific condition. We investigated the amount of missing patient data for primary outcomes in Cochrane systematic reviews, and surveyed the Co-ordinating Editors of Cochrane Review Groups (CRGs) on issues related to the standardization of outcomes in their CRG’s reviews. These groups are responsible for the more than 7,000 protocols and full versions of Cochrane Reviews that are currently available, and the several hundred new reviews published each year, presenting the world’s largest collection of standardized systematic reviews in health care.
Methods
Using an unselected cohort of Cochrane Reviews, we calculated and presented the percentage of missing patient data for the primary outcome measure chosen for each review published by each CRG. We also surveyed the CRG Co-ordinating Editors to see what their policies are with regards to outcome selection and outcomes to include in the Summary of Finding (SoF) tables in their Cochrane Reviews. They were also asked to list the main advantages and challenges of standardizing outcomes across all reviews within their CRG.
Results
In one fifth of the 283 reviews in the sample, more than 50% of the patient data for the primary outcome was missing. Responses to the survey were received from 90% of Co-ordinating Editors. Thirty-six percent of CRGs have a centralized policy regarding which outcomes to include in the SoF table and 73% of Co-ordinating Editors thought that a COS for effectiveness trials should be used routinely for a SoF table.
Conclusions
The reliability of systematic reviews, in particular meta-analyses they contain, can be improved if more attention is paid to missing outcome data. The availability of COSs for specific health conditions might help with this and the concept has support from the majority of Co-ordinating Editors in CRGs.
doi:10.1186/1745-6215-14-21
PMCID: PMC3575292  PMID: 23339751
COMET; Cochrane review groups; Co-ordinating editors; Core outcome set; ORBIT; Systematic reviews; Survey
18.  What do letters to the editor publish about randomized controlled trials? A cross-sectional study 
BMC Research Notes  2013;6:414.
Background
To identify published letters to the editor (LTE) written in response to randomized controlled trials (RCTs), determine the topics addressed in the letters, and to examine if these topics were affected by the characteristics and results of the RCTs.
Methods
Comparative cross-sectional study of a representative sample of RCTs from a set of high-impact medical journals (BMJ, Lancet, NEJM, JAMA, and Annals of Internal Medicine). RCTs and their published LTE were searched from these 5 journals in 2007. Data were collected on RCTs and their characteristics (author affiliation, funding source, intervention, and effect on the primary outcome) and the topics addressed in published LTE related to these RCTs. Analysis included chi-square and regression analysis (RCT characteristics) and thematic analysis (LTE topics).
Results
Of 334 identified RCTs, 175 trials had at least one LTE. Of these, 381 published LTE were identified. Most RCTs, tested drug interventions (68%), were funded by government (54%) or industry (33%), and described an intervention that had a positive impact on the primary outcome (62%). RCT authors were primarily affiliated with an academic centre (78%). Ninety percent of the 623 LTE topics concerned methodological issues regarding the analysis, intervention, and population in the RCT. There was a significant association between funding source and impact on outcomes (p = 0.002) or type of intervention tested (p = 0.001) in these trials. Clinical and “Other” LTE topics were more likely to be published in response to a government funded RCT (p = 0.005 and p = 0.033, respectively); no other comparisons were significant.
Conclusions
This study showed that most LTE are about methodological topics, but found little evidence to support that these topics are affected by the characteristics or results of the RCTs. The lack of association may be explained by editorial censorship as a small proportion of LTE that are submitted are actually published.
doi:10.1186/1756-0500-6-414
PMCID: PMC3852599  PMID: 24124753
Letters to the editor; Randomized controlled trials; Journalogy
19.  Conflicts of interest in biomedical publications: considerations for authors, peer reviewers, and editors 
Croatian Medical Journal  2013;54(6):600-608.
This article overviews evidence on common instances of conflict of interest (COI) in research publications from general and specialized fields of biomedicine. Financial COIs are viewed as the most powerful source of bias, which may even distort citation outcomes of sponsored publications. The urge to boost journal citation indicators by stakeholders of science communication is viewed as a new secondary interest, which may compromize the interaction between authors, peer reviewers, and editors. Comprehensive policies on disclosure of financial and non-financial COIs in scholarly journals are presented as proxies of their indexing in evidence-based databases, and examples of successful medical journals are discussed in detail. Reports on clinical trials, systematic reviews, meta-analyses, and clinical practice guidelines may be unduly influenced by author-pharmaceutical industry relations, but these publications do not always contain explicit disclosures to allow the readers to judge the reliability of the published conclusions and practice-changing recommendations. The article emphasizes the importance of adhering to the guidance on COI from learned associations such as the International Committee of Medical Journal Editors (ICMJE). It also considers joint efforts of authors, peer reviewers, and editors as a foundation for appropriately defining and disclosing potential COIs.
doi:10.3325/cmj.2013.54.600
PMCID: PMC3893982  PMID: 24382859
20.  News from the editors of Fluids and Barriers of the CNS 
This editorial announces a new affiliation between Fluids and Barriers of the CNS (FBCNS) and the International Brain Barriers Society (IBBS) with mutual benefits to the journal and to society members. This is a natural progression from the appointment of two new Co-Editors in Chief: Professor Lester Drewes and Professor Richard Keep in 2013. FBCNS provides a unique and specialist platform for the publication of research in the expanding fields of brain barriers and brain fluid systems in both health and disease.
doi:10.1186/2045-8118-11-13
PMCID: PMC4060582  PMID: 24940481
21.  Are reviewers suggested by authors as good as those chosen by editors? Results of a rater-blinded, retrospective study 
BMC Medicine  2006;4:13.
Background
BioMed Central (BMC) requires authors to suggest four reviewers when making a submission. Editors searching for reviewers use these suggestions as a source. The review process of the medical journals in the BMC series is open – authors and reviewers know each other's identity – although reviewers can make confidential comments to the editor. Reviews are published alongside accepted articles so readers may see the reviewers' names and recommendations.
Our objective was to compare the performance of author-nominated reviewers (ANR) with that of editor-chosen reviewers (ECR) in terms of review quality and recommendations about submissions in an online-only medical journal.
Methods
Pairs of reviews from 100 consecutive submissions to medical journals in the BMC series (with one author-nominated and one editor-chosen reviewer and a final decision) were assessed by two raters, blinded to reviewer type, using a validated review quality instrument (RQI) which rates 7 items on 5-point Likert scales. The raters discussed their ratings after the first 20 pairs (keeping reviewer type masked) and resolved major discrepancies in scoring and interpretation to improve inter-rater reliability. Reviewers' recommendations were also compared.
Results
Reviewer source had no impact on review quality (mean RQI score (± SD) 2.24 ± 0.55 for ANR, 2.34 ± 0.54 for ECR) or tone (mean scores on additional question 2.72 ANR vs 2.82 ECR) (maximum score = 5 in both cases). However author-nominated reviewers were significantly more likely to recommend acceptance (47 vs 35) and less likely to recommend rejection (10 vs 23) than editor-chosen reviewers after initial review (p < 0.001). However, by the final review stage (i.e. after authors had responded to reviewer comments) ANR and ECR recommendations were similar (65 vs 66 accept, 10 vs 14 reject, p = 0.47). The number of reviewers unable to decide about acceptance was similar in both groups at both review stages.
Conclusion
Author-nominated reviewers produced reviews of similar quality to editor-chosen reviewers but were more likely to recommend acceptance during the initial stages of peer review.
doi:10.1186/1741-7015-4-13
PMCID: PMC1482713  PMID: 16734897
22.  What do the JAMA editors say when they discuss manuscripts that they are considering for publication? Developing a schema for classifying the content of editorial discussion 
Background
In an effort to identify previously unrecognized aspects of editorial decision-making, we explored the words and phrases that one group of editors used during their meetings.
Methods
We performed an observational study of discussions at manuscript meetings at JAMA, a major US general medical journal. One of us (KD) attended 12 editorial meetings in 2003 as a visitor and took notes recording phrases from discussion surrounding 102 manuscripts. In addition, editors attending the meetings completed a form for each manuscript considered, listing the reasons they were inclined to proceed to the next step in publication and reasons they were not (DR attended 4/12 meetings). We entered the spoken and written phrases into NVivo 2.0. We then developed a schema for classifying the editors' phrases, using an iterative approach.
Results
Our classification schema has three main themes: science, journalism, and writing. We considered 2,463 phrases, of which 87 related mainly to the manuscript topic and were not classified (total 2,376 classified). Phrases related to science predominated (1,274 or 54%). The editors, most of whom were physicians, also placed major weight on goals important to JAMA's mission (journalism goals) such as importance to medicine, strategic emphasis for the journal, interest to the readership, and results (729 or 31% of phrases). About 16% (n = 373) of the phrases used related to writing issues, such as clarity and responses to the referees' comments.
Conclusion
Classification of editorial discourse provides insight into editorial decision making and concepts that need exploration in future studies.
doi:10.1186/1471-2288-7-44
PMCID: PMC2121101  PMID: 17894854
23.  Letter to the editor: healthy alternatives to trans fats 
Consumption of trans fats is associated with an increase of cardiovascular disease (CVD) risk. To comply with regulatory policies and public health authorities recommendations, trans fats should be replaced in food products. The study by Sundram et al. (Nutrition & Metabolism 2007, 4:3) reporting the effect on CVD risk factors of interesterified fat (IE) and partially hydrogenated soybean oil (PHSO) compared to palm olein (POL) has been critically analyzed. The study design and in particular the composition of the tested fats was not suitable to properly answer the question raised regarding the effect of alternative ingredients to trans fats on plasma lipids. The observed effects are divergent with predicted data derived from the literature model consolidated using the individual results of 60 randomized clinical trials. The results of the study published by Sundram and co-workers have to be considered with awareness.
doi:10.1186/1743-7075-4-10
PMCID: PMC1867814  PMID: 17462099
24.  Consensus and contention regarding redundant publications in clinical research: cross-sectional survey of editors and authors 
Journal of Medical Ethics  2003;29(2):109-114.
Objectives: To examine the perspectives of journal editors and authors on overlapping and redundant publications in clinical research.
Design: Pretested cross-sectional survey, containing both forced choice and open ended questions, administered by mail to the senior editors (N=99) and one randomly selected author (N=99) from all journals in the Abridged Index Medicus (1996) that published clinical research.
Main measurements: The views of editors and authors about the extent of redundant publications, why they occur, how to prevent and respond to cases, and when the publication of overlapping manuscripts is justified.
Results: Seventy two per cent (N=71) of editors and 65% (N=64) of authors completed the survey. There was consensus between both groups that redundant publications occur because authors feel the pressure to publish and journals do not do enough to publicise, criticise, and punish cases, and that the publication of most types of overlapping articles is unacceptable. Sixty seven per cent of authors but only 31% of editors felt, however, that it was justified to publish an overlapping article in a non-peer reviewed symposium supplement, and 68% of editors but 39% of authors supported imposing restrictions on guilty authors' future submissions. In written comments, 15% to 30% of both groups emphasised that it was justified to publish overlapping articles when there were different or non-English-speaking audiences, new data, strengthened methods, or disputed findings.
Conclusions: Editors, authors, and other academic leaders should together develop explicit guidelines that clarify points of contention and ambiguity regarding overlapping manuscripts.
doi:10.1136/jme.29.2.109
PMCID: PMC1733707  PMID: 12672892
25.  The PREP suite: predictive RNA editors for plant mitochondrial genes, chloroplast genes and user-defined alignments 
Nucleic Acids Research  2009;37(Web Server issue):W253-W259.
RNA editing alters plant mitochondrial and chloroplast transcripts by converting specific cytidines to uridines, which usually results in a change in the amino acid sequence of the translated protein. Systematic studies have experimentally identified sites of RNA editing in organellar transcriptomes from several species, but these analyses have not kept pace with rate of genome sequencing. The PREP (predictive RNA editors for plants) suite was developed to computationally predict sites of RNA editing based on the well-known principle that editing in plant organelles increases the conservation of proteins across species. The PREP suite provides predictive RNA editors for plant mitochondrial genes (PREP-Mt), for chloroplast genes (PREP-Cp), and for alignments submitted by the user (PREP-Aln). These servers require minimal input, are very fast, and are highly accurate on all seed plants examined to date. PREP-Mt has proved useful in several research studies and the newly developed PREP-Cp and PREP-Aln servers should be of further assistance for analyses that require knowledge of the location of sites of RNA editing. The PREP suite is freely available at http://prep.unl.edu/.
doi:10.1093/nar/gkp337
PMCID: PMC2703948  PMID: 19433507

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