Public Library of Science

Round-up of PLoS ONE Articles in the Year's Science Superlatives

Rebecca Walton — Tue, 6 Jan 2009 09:01:14 -0800

A number of papers published in PLoS ONE in 2008 have been featured in some recent round-ups of the year's best—and quirkiest—research. From worm grunting to an explanation for the superior sound of Stradivarius violins compared with modern violins, as ever, the highlighted articles cover a wide range of different scientific disciplines and topics.

An article by Haoran Wang and colleagues reporting on the high-frequency calls made by male mice during mating (which the researchers found to be associated with genes that control positive emotions) was highlighted in New Scientist's round-up of the top 10 genetics stories of 2008.

Charles Limb and Allen Braun's article on the neural activity involved in jazz improvisation featured in Nature's Research Highlights of 2008 (as was a PLoS Biology article on the control of gene expression in yeast).

A study by University of Florida researchers, in which the authors proposed a three-stage model for the colonization of the Americas, made #10 in Discover Magazine's top 100 stories of the year.

Ken Catania's paper on the workings of worm grunting, a technique practiced in parts of the southeastern United States to bring worms to the surface of the ground to collect them to use as bait, appeared in the top 10 ScienceNOWs of 2008 selected by Science magazine. The PLoS ONE article contains a number of movies for those whose curiosity for this topic has not yet been sated.

An article by Janet Mann and colleagues, which posed the age-old question, “Why Do Dolphins Carry Sponges?” and in which the researchers describe the first clear-cut example of tool use in dolphins, appeared in Science News’s review of the year in life sciences.

Also included in a Science News round-up of the year was a study by Andrew Pask and colleagues, which made the list of 2008’s best stories on genes and cells. The researchers inserted genes extracted from Tasmanian tiger specimens into a mouse embryo. This was the first time that DNA from an extinct animal has functioned inside a living host.

Cosmos magazine ranked Joydeep Bhattacharya's research on the "Eureka moment" sometimes experienced in problem-solving among its top 10 news stories of the year.

Pieter Niewiarowski's study, published in PLoS ONE in May shed light on the mechanics of geckos' sticky feet and was highlighted in The Science Channel's list of the top 10 science stories of 2008.

In an article published in July, Dutch researcher Berend Stoel, in collaboration with luthier Terry Borman, reported that it is the wood density of certain classical violins (such as those made by Stradivari) that gives them a superior sound quality. Wired ranked its story on the study as one of the 13 most popular science stories of the year.

Finally, from the melodic to the mysterious, an article by Amir Grosman and colleagues in the Netherlands, who reported the finding that parasitoid wasp larvae, having partially developed inside caterpillars, manipulate their hosts into protecting them by acting as bodyguards. The study made New Scientist's list of the year's weirdest animals.

It's great to see these articles, which were all covered by the press and in the blogosphere at the time of original publication, being highlighted again, along with those studies which were blogged as part of the recent PLoS ONE second birthday synchroblogging competition. We hope that articles published in PLoS ONE will continue to make appearances in the media throughout 2009 and beyond!

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New Section Editor Interview - Bernhard Baune

Peter Binfield — Mon, 22 Dec 2008 08:56:19 -0800

Bernhard Baune is the Section Editor in charge of Neuroscience and Psychiatry (one of our largest fields, with 650 papers listed in this category at the present time) at PLoS ONE. His personal fields of specialization are Psychiatric Neuroscience, Biological Psychiatry and Epidemiology in Psychiatry. When he’s not busy working on papers for PLoS ONE, he has a full time position as the Professor of Psychiatry and Psychiatric Neuroscience at James Cook University, Australia.

PB: Bernhard, please tell me a bit more about your background

BB: My clinical background is in psychiatry, and my research background is mainly in the neuroscience and epidemiology of psychiatric disorders. Our research approach is broad and involves basic science such as animal models and clinical application such as pharmacogenetics. We currently focus on mood disorders and have a special interest in cognitive functioning and performance in mood disorders. Here at James Cook University, we have a mood disorders research program and specifically look at applied Neuroscience methods which have a translational approach to clinical applications.

PB: And how large is your research group

BB: At the moment we have 8 people working in the group. We are currently extending into the area of neuroprotection in neuropsychiatric illnesses and specifically we are exploring a protein with the potential of neuroprotection.

PB: You have recently been handling the editorial oversight of a Collection of papers for our forthcoming ‘Stress and Depression’ Collection (scheduled to publish in January 2009). Can you tell me a bit about your work on that Collection?

BB: The Collection is a highly relevant topic, for a number of reasons. On the one hand it reflects the research traditions in that area, but on the other hand it reflects the need for research on depression to look at gene/environmental interactions. Therefore I found it very interesting from the beginning and was happy to become involved as the Academic Editor for it. A number of very interesting papers were submitted, really reflecting different areas of relevance to the field – from animal through to clinical research.

PB: And what was the quality of those papers like?

BB: I would say they were all ‘high’ to ‘top’ quality papers and if I compare those papers to papers from other journals for which I review, then I would say they are of the same quality as top journals. The only difference I might observe is that some of the papers were more specific in their topics as opposed to be being ‘broad’ in their approach, which is often the criteria of more traditional journals which may seek broader papers to attract a wider readership. Papers in my field sometimes deal with very specific and detailed mechanisms for example, so I think that while they may have a tendency to be more specific and detailed, the good thing is that the journal gives the authors the opportunity to publish that type of work.

PB: And would you say that this is a general feature of PLoS ONE papers – that authors have the freedom to be more detailed in their submissions and don’t feel that they need to write articles just to satisfy a broad readership?

BB: Yes, that is my impression. I wouldn’t say that is the main characteristic of PLoS ONE papers but certainly a proportion of papers submitted do have that profile. I think that’s very good, because its really about the detailed science of the paper rather than the ‘message’.

PB: I think that’s really one of the main advantages of PLoS ONE. Because we do not sell our content, we don’t have to publish only the most ‘impactful’ or ‘interesting’ articles (which might improve our ‘salability’). Therefore, authors are able to write their article according to the needs of their science - and this is very liberating for many of them.

PB: And how do you work, in your role as Section Editor?

BB: As a Section Editor I receive all papers submitted in my area of neuroscience and psychiatry. I look at the paper, and read it to evaluate the exact topic before assigning it to the Academic Editor whom I feel is best qualified to handle that particular paper. Then the papers are sent our for peer review, and from my point of view the peer review process is identical to that of other journals – at least 2 external peer reviewers are asked for their expert opinion; those comments are sent back to the authors; and they are required to reply appropriately to improve their manuscript before a final decision is made by the Academic Editor. This process is fairly quick, by which I mean our turnaround time is fast.

PB: I agree about the speed. For example, we are online only and so are able to publish final articles on a daily schedule. As a result, our current performance from final acceptance to online publication is just 26 days on average which I believe is significantly faster than the majority of journals, which typically still adhere to an ‘issue based’ publication schedule.

PB: How much time would you say you spend on PLoS ONE

BB: I work on it on a daily basis, as I need to keep track of newly submitted papers in my section. I spend maybe an hour a day on the journal.

PB: And what is the most important thing that scientists should understand about PLoS ONE. Is it simply the fact we are Open Access? Or are there more interesting things that people should know about?

BB: The most important thing to know is that the selection criteria is dependant on the quality and methodology of the research, rather than interest level. That is important because there is a lot of good research out there which deserves publication. Secondly, the broadness of the topics, both within a section but also overall, is very important. This means that the diverse research conducted at various labs around the world has the opportunity to be published. And finally, the speed of publication is also very important, although other journals can also be fast so I would place this third.

PB: And what about Open Access in general? What is your opinion of this publication method?

BB: Open Access is very good because people who do not engage with research on a day to day basis, or only on a more occasional basis, have easy access to the literature.

PB: That’s a very good point, I think. Is there anything else you would like to add to this interview?

BB: Well, PLoS ONE is a great idea with great potential. I would also like to say that the PLoS ONE team is really fantastic – speedy responses; good high quality feedback; very efficient; very knowledgeable. I really appreciate that communication with the team.

PB: That’s a very nice note to end on Bernhard, and I am sure the PLoS ONE team will be very pleased to hear those comments. Thank you very much.

If you would like to experience PLoS ONE for yourself, the Open Access, the speed and the personable service, submit your work to us today.

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A perfect time to reflect (and act?)...

Mai Wong — Mon, 22 Dec 2008 05:37:59 -0800

…Is this to do with the coming of:
1. the festive season;
2. a new year;
3. the incessant reminders of the credit crunch;
4. being a psychiatrist;
5. the recent systematic review on the prevalence of mental disorders in the homeless in PLoS Medicine (the first paper I saw through the whole editorial process); OR
6. the end of my time at PLoS Medicine as an editorial intern

I would think it is probably ALL of the above. I started as an editorial intern at PLoS Medicine in April - I have to confess that it was the organization that attracted me and not the opportunity to be involved in editorial work although this has been extremely educational and challenging.

My career path has been far from conventional to date, veering off the beaten track that tends to be quite prescriptive in the medical world. Hence, I can see quite clearly why I would have been attracted to an organization like PLoS, “a nonprofit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource.” The core principles in itself are surely enough to ignite, at the very least, a sense of curiosity. As with all organizations, it comes down to the people and it has been particularly inspiring and educational to have had the opportunity working with the ones behind PLoS Medicine (the monthly editorials is a platform for the editors to have a “shout” and I think a great insight into what counts for people is what they shout about…so have a look).

Over the months, I have become acquainted with debates on
Open Access, Impact Factors, Reporting Guidelines, Competing Interests…issues, that may appear on first glance to be only of interest to editors, researchers etc but I have started to realize the large impact they actually have on us all. The reason is that regardless of where you live, what social economic group, race, age, educational background/level etc you are/have – one thing that helps make life better is being in good health (needless to say that includes mental health). There are many ways in which, unfortunately, we will all in our lifetime have both direct and indirect experience of health problems and it is at these times that I want to know that healthcare providers in any and every part of the world will have access to the best and most relevant, up-to-date information when making treatment decisions; that funders of research, who might be seen as the care-takers of everyone’s invested interest, are making the decision to invest in research projects that show potential to help us better understand diseases and their treatments based on objectivity.

Healthcare is complex – it can also be very expensive and emotive. Difficult decisions and priorities have to be made – demand will outstrip supply. I don’t think it is rocket science to realize that this can only be helped by openness and transparency so that objective scrutiny can be used to make judgments on what we need to prioritize and pursue.

We all have agendas, declared or undeclared, conscious or not (and we are all open to influence)…mine is influenced by my chosen medical specialty - I am a psychiatrist. I find the mind-body interface fascinating and think it is virtually impossible to detach one’s mental health from any physical condition. Also, I think that being interested in the wider world and the welfare of those who co-habit it is greatly beneficial to one’s own mental health – the rewards of giving/caring.

Therefore, I will be leaving this experience with a better understanding of why the notion of a Public Library of Science is best served with the word ‘Public’ leading the way – well, what I mean is that anyone can access what’s in it freely. In my opinion, PLoS isn’t just another publishing platform or collection of journals; it is the start of a movement where we the beneficiaries (everyone) need to start demanding that in exchange for our time, money and “pathologies”, the many industries involved and have evolved in the generic healthcare/scientific world need to realize that we want transparency and accessibility.

So, would I recommend being an editorial intern at PLoS Medicine?…YES, in fact, I would go further and recommend that everyone should grab any opportunity that comes their way to be involved at any level with PLoS…this may include just reading a paper and knowing that everyone else can!!

Lastly, please indulge me by allowing me to publicly extend a BIG THANK YOU to the team at PLoS Medicine (and the rest of PLoS, of course) for giving me this opportunity to learn from you and to have worked with you.

Happy holidays and may the challenges of 2009 help you expand your horizons.

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Einstein was smart, but Could He Play the Violin? - the winner of the synchroblogging contest

Bora Zivkovic — Sat, 20 Dec 2008 11:00:53 -0800

Today is PLoS ONE's second anniversary and we're celebrating by announcing that the winner of the second PLoS synchroblogging competition is SciCurious of the Neurotopia 2.0 blog.

"This fluent post captures the essence of the research and accurately communicates it in a style that resonates with both the scientific and lay community" - Liz Allen, PLoS.

Here is the winning entry, cross posted in its entirety:

====================

Einstein was smart, but Could He Play the Violin?

I already wrote one entry for PLoS ONE's second birthday, but I'm feeling sparky today, and I think I like this paper better.

I don't know about you guys, but when I was a sprog, my parents dragged me to music lessons. LOTS of music lessons. As of right now, I have been producing music of some type for the past 21 years straight. And I LOVE it.

Of course, I didn't always love it. I remember my mother dragging me and my brother to lessons, making us sit down every day and practice (I was, and still am, no good with the practicing), and the fear and shakiness of recitals (heck, I still get that, and it's been 21 years). In her time, Sci has actually "mastered" (it's a debatable point), three different instruments ('instruments' is a loose term), and still uses one of them professionally on occasion. And if you can guess what they are, Sci will...do something cool. Like send you one of her favorite books. Or perhaps a tshirt with a molecule on it. Or perhaps some of her delicious cookies. Obviously, you can only guess if you don't KNOW already (that means you, Dad). So there you go, contest open.

Anyway, years and years of music lessons. But the question is: did they do me any good? Does playing 'Baby Mozart' really do anything, and is anything achieved by starting your child on Suzuki when they are 2, other than the pain and misery of your child, and possibly an eventual love of music? Can it, perhaps, make me SMARTER?

Forgeard et al. "Practicing a musical instrument in childhood is associated with enhanced verbal ability and nonverbal reasoning" PLoS ONE, 2008.

And for the record, Einstein did play the violin. Apparently he was quite good.

There actually are several studies out there that show that techniques that you learn can "transfer" to other techniques, giving you a bit of an edge. This works best when you're performing skills that are very similar to each other (like learning how to estimate the area of a square, and then learning how to estimate the area of a triangle). We know this happens for musicians in the development of fine motor skills. Once you've been playing the violin for a while, other things that require fine motor skills will come to you a bit easier (perhaps we should train all would-be surgeons on musical instruments, if you can master playing Rachmaninoff, brain surgery should be a piece of cake).

Of course, most of the studies that have been done are correlational in nature. Kids who play musical instruments have better motor skills. This could be due to the music, or the kids could play music because they have good motor skills. Good motor skills could be a development of things like the higher socio-economic class that often goes along with being taught music as a child, and thus parents are maybe able to put more effort to their development. The possibilities go on. Correlation is NOT causation.

The same thing goes for the correlation between musical learning and IQ. There was a modest correlation, but it could be just the effect of the extra lessons the kids were receiving, resulting in more time spent on focused attention and mastering a skill. Significant correlations have also been shown for music and verbal and language skills. Music lessons have been found to be correlated with increases in reading ability and phonetic comprehension. This actually leads me to a question: if language, reading, and phonetic comprehension are related to the pitch and tone of words, do children who are tone deaf have a harder time mastering reading and verbal skills? I think this might warrant a future PubMed search.

Unfortunately, all the previous tests tended to focus on the "transfer" of skills to not very related fields, like IQ. So in this study, the authors wanted to look at the effects of music learning on "near" transfers, skill closely related to music training: spatial reasoning, verbal abilities, nonverbal, and mathematical. They also looked for VERY closely related skills: fine motor control and auditory skill.

They grabbed a whole bunch of kids around 8-11 years old. Some played musical instruments, some didn't (one of the problems with this study to me is that the control group is a good bit small than the instrumental group, 41 musicians vs 18 non). Kids were controlled for the socio-economic class of the parents. Average length of music training was close to five years. They also divided the kids up by whether or not they got Suzuki training, but ended up grouping them together, as Suzuki effects were no different from other instrumentalists.

Dang, they didn't graph their data. Well, I shall fix. Because I can. People should be so grateful I do all their graphing...

There you go. So, as you can see from the graph (the pretty, pretty graph), musical kids scored a lot better on fine motor skills for left and right hand (the first two sets of bars). This is pretty expected, if you're using fine motor skills a lot, presumably you'll get better at them. The musical kids also did better when distinguishing tones and following melody lines, though interestingly, they didn't show any improvements in rhythm. I wonder if this has anything to do with the kids of music the kids were studying. There wasn't a single drummer in the bunch, it was all either piano or stringed instruments.

And finally, the kids with musical training scored a lot better (I know it doesn't look like it, but the MANCOVA analysis uncovered a difference) on vocabulary testing. They outperformed their non-musical counterparts in both verbal ability (vocabulary) and non-verbal reasoning skills. They didn't find any differences in math or spatial reasoning.

The authors hypothesize that music training may transfer skills to some other related domains. The other hypothesis is that music training doesn't enhance a specific skill set, but rather your general intellectual ability. This would mean they would score higher on every test given. In fact, they DID score higher, but most of the time the scores didn't reach significance.

Still, remember this is correlation, not causation. Families were of similar socio-ecoomic class and education, but that doesn't mean they are all similar parents. Kids who take music lessons may have parents that are more involved in their intellectual development. Kids that persist in taking music lessons for a good chunk of time may have superior motivation. Correlation =/= causation.

But it's still a cool paper, and no matter what, it's quite clear that music lessons didn't HURT. Time to tape your poor child to the piano bench!

Marie Forgeard, Ellen Winner, Andrea Norton, Gottfried Schlaug (2008). Practicing a Musical Instrument in Childhood is Associated with Enhanced Verbal Ability and Nonverbal Reasoning PLoS ONE, 3 (10) DOI: 10.1371/journal.pone.0003566

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Live today - enter PLoS ONE's second birthday synchro blog competition

Liz Allen — Thu, 18 Dec 2008 09:55:08 -0800

Today's the day. If you are going to enter and possibly win a bag of PLoS swag, we'd like to read your blog post. If you are new to the competition you can read up on it here. Some early entries include:

Ed Yong of Not Exactly Rocket Science posted "Predatory slime mould freezes prey in large groups".

Scicurious of Neurotopia (version 2.0) posted "Why Did the Dolphin Carry a Sponge"?

Scicurious of Neurotopia (version 2.0) also posted "Einstein was smart, but Could He Play the Violin"?

Allyson of Systems Biology & Bioinformatics (Semantically Speaking)posted "One way for RDF to help a bioinformatician build a database: S3DB".

Simon Cockell of Fuzzier Logic posted "Contextual Specificity in Peptide-Mediated Protein Interactions".

The entries are coming in so thick and fast that I can't keep up, so these are just a sample.

Good luck and happy second birthday (on Saturday) to PLoS ONE.

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Tweet tweet - PLoS on Twitter

Liz Allen — Mon, 15 Dec 2008 16:04:29 -0800

My initial early attempts to start Twittering for PLoS were woefully inadequate. I have since cleaned up the evidence of my sad and sorry start (Twitter has a helpful delete function). Not only could I not understand what I was meant to be using it for (or even how to use it at all) but I was surrounded by people sharing the personal minutiae of their lives on a minute by minute basis - why would anyone be interested in that I thought?

It turned out that folks weren't captivated by the small stuff but that they were interested in what influential folks like Guy Kawasaki were paying attention to and, curiously, the inner workings of organizations such as SouthWest Air.

It was when I heard that the Obama grass roots election campaign folks had been using it to great effect and I read a blog post from Tim O'Reilly entitled Why I Love Twitter, that I decided to try harder and see if I too could learn to appreciate this social media tool and use it to keep our community informed of what we are thinking, following and watching on a regular basis. I was also encouraged by new PLoS IT hire and Twitterer Joey O.

In a nutshell, Twittering is "microblogging". It lets me (and hopefully other PLoS folks soon) share small tidbits about the things that we are doing in 140 characters or less (as you type it reduces the number of characters left available to you and gives you a red warning sign once you've reached your max). Lengthy PLoS article URL's are miraculously shrunk to itty bitty proportions thanks to their automatic tiny url functionality. Updating is possible via your cell phone or the web.

So does it work? Yes, I am happy to report that I've had a couple of good experiences where I've released information about an article that was breaking in the media and seen coverage of it grow as a direct result of the Tweet (the slightly odd but in its own way perfectly logical name given to single postings on Twitter), which was very pleasing.

You can check out all PLoS related Tweets made by me or anyone else who posts about PLoS in this search. As you can see, plenty of people across the world have plenty to say about us.

If you want to start following PLoS, you need to join Twitter and then become a follower of PLoS - you'll be in limited (but excellent) company, right now we only have 38 followers, but we sure would like more so please join us.

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PLoS ONE @ Two - second birthday synchroblogging competition

Liz Allen — Tue, 9 Dec 2008 10:24:47 -0800

PLoS ONE turns two this December. For our community celebration we're going to run our second synchroblogging competition. The first one was organized to celebrate the first ever Open Access Day this year and resulted in 400 posts and two winners Greg Laden and Dorothea Salo who each received some nice swag. This time, we've partnered up with our friends at researchblogging.org, the site that aggregates blogs about peer-reviewed research, to create this competition.

To take part, all you have to do is:

1. Register on researchblogging.org

2. On December 18, 2008, blog about a PLoS ONE paper past or present and use the icon provided by researchblogging.org so the link to your post appears on their site (if you have any technical difficulties doing this simply send your post to Bora Zivkovic, bzivkovic@plos.org, our community manager and he'll help you out).

3. We'll also use Google News/Technorati to track entries - to make this easier please use the phrase "PLoS ONE @ Two" in your post. Finally, we'd like you to try and track back to our original article, here are some instructions.

We've assembled a small team of judges who will review all these posts and vote on a winner. They will be looking for well organized posts from qualified individuals that set the research in broader context and add to the debate around the paper by posing questions on it.

Dave Munger - writer, science blogger on Cognitive Daily and the founder and manager of researchblogging.org
Bora Zivkovic - scientist, blogger from A Blog Around the Clock and Community Manager for PLoS ONE.
Jason Stajich - postdoc at UC Berkeley in the Department of Plant and Microbial Biology
Liz Allen - PLoS

The winning post will have their entry cross posted on the PLoS ONE Blog and A Blog Around the Clock. They will also receive a bag of swag that includes: the new PLoS Water bottle (H2go brand) and a couple of cool PLoS t-shirts.

In your eagerness to get involved, please don't post before December 18, 2008, we really want to make a noise for our birthday.

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Interview with a Chinese author

Peter Binfield — Mon, 8 Dec 2008 12:09:51 -0800

Since launch, PLoS ONE has published the work of over 23,000 authors worldwide, including many from China.

As part of our campaign to highlight publications which have received good article level metrics (such as citations as counted by Google Scholar), I asked a corresponding Chinese author, Tian Kegong, Director of the Veterinary Diagnosis Lab, China Animal Disease Control Center Beijing, PR of China, about his experiences of publishing the paper “Emergence of Fatal PRRSV Variants: Unparalleled Outbreaks of Atypical PRRS in China and Molecular Dissection of the Unique Hallmark” by Tiang et al, with us.

Q. Why did your team choose PLoS ONE to publish this work?

A. PLoS Journals have a good reputation in the field of science - we were glad that our paper could be published in PLoS ONE. In addition, Open Access makes our study, which is vitally crucial for other governments and scientists to defend against the epidemic of PRRS in China, available to everyone, anywhere. The online commenting tool that can be used after publication provides a platform to exchange ideas - this is crucial for us and offered the opportunity to facilitate cooperation between other scientists and my team in the field of PRRSV.

Q. Could you comment on the topic of this paper and why you think it was well received?

A. I think the article was appreciated because it covered a reasonable amount of important scientific ground. 1. The pathogenesis of so-called "high fever " disease, which spread to more than 10 provinces and affected over 2,000,000 pigs with about 400,000 fatal cases, was first determined and reported in the form of academic publication. This study helped other scientists in the field to become oriented to the current research direction. 2. This paper also brought forward the concept of highly pathogenic PRRSV (HP-PRRSV) for the first time. Based on the systematical study including the clinical feature, histopathology, molecular epidemiology and molecular virology, some special features were found that were quite different from the typical PRRSV isolates, such as high fever, high mortality and two distinct deletions in the non-structural protein 2 (NSP2). 3. The JXA1 PRRSV strain, mentioned in this paper, was the seed virus developed for a inactivated vaccine that was the key role to control the epidemic of HP-PRRSV in the past year, and a attenuated vaccine that had passed the evaluation of National Animal clinical trial. The inactivated vaccine had received a temporary certificate of veterinary drugs. 4. We had successfully developed two HP-PRRSV vaccine including the inactivated vaccine and attenuated vaccine, which played an important role in the controlling the disease over the past year. Meanwhile, the RT-PCR and Real-Time fluorescent PCR detection methods had also been established to monitor epidemiology of HP-PRRSV from 2006 to 2008, and the characteristics of HP-PRRSV virulence and entire genome sequence data were got and analyzed through newly isolated virus in the interim.

Q. What are you working on now?

A. At present, we are focusing on the virulence determinants and genetic evolution of HP-PRRSV. a) The entire genomes sequence data were compared and analyzed between the JXA1 strain , its cell-induced virus, newly isolated virus of HP-PRRSV, and other typical isolates; b) The HP-PRRSV infectious clone are being established to explore the pathogenic mechanism through Reverse Genetics.

Q. What was your experience of publishing with us like, and would you do it again?

A. I was really impressed by the experience of the rigorous editorial process and constructive comments, supplied by good editors and good reviewers. These undoubtedly improved our manuscript. The quick service ensured that the research was published in good time. Thus, we’d like to do it again. We are willing to contribute our latest work to your journal. We hope to establish a good long-term cooperative relationship in the future, and show our best work in PLoS ONE.

We are happy to publish work from China and invite you to submit your research wherever you live.

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Blogging on bias

Andrew Hyde — Mon, 8 Dec 2008 07:20:02 -0800

Publication bias became a big blogging topic last week as a PLoS Medicine paper was picked up by several influential sites. Lisa Bero and colleagues found that a quarter of trials submitted to the Food and Drug Administration between 2001 and 2002 in support of new drugs applications remain unpublished a year after the fact. The study also found that among the published results, unexplained discrepancies between the FDA submission and the published studies tended to lead to more favourable presentations of the drugs.

For the past two weeks it has been the most viewed paper on the PLoS Medicine website and discussion of the paper has passed from blog to blog, including:

- Wired ("Drug Companies Cook Books, Misleading Doctors").

The Wired science blog, which has resulted in fifteen comments so far, highlights the discrepancy found in the study between results submitted to the FDA and those published in medical journals, and the key pieces of trial data that vanished in the published results. "The main thing that jumped out at me was the addition and deletion of primary outcomes. Those are the most important outcomes of a trial. To find that one disappeared from a paper, or just appeared in a paper, is pretty amazing to me," Lisa Bero is quoted in the piece.

- Economist ("Absence of Evidence").

There are twelve comments in response to the Economist's question: "Do drug firms suppress unfavourable information about new products?" The print and online versions of the Economist also make reference to the perspective by An-Wen Chan that we published alongside the study, which argues that all key trials documents should be made public. "It has taken decades for trial registration and results disclosure to be implemented; hopefully, for the sake of patients, public access to full protocols and regulatory agency submissions will come much sooner", says Chan in the perspective.

How else to fix the discrepancy between the trials submitted to the FDA and the published results? One of the more cynical comments about the research in response to the Wired blog ( "Hmmmm, big corps, unethical, self serving... TELL ME SOMETHING I DON'T ALREADY KNOW! Better yet, give me some suggestions regarding what I can do about it" ) is answered in Smooth Pebbles, a blog by David Dobbs, a freelance science writer for the New York Times amongst others. He quotes Lisa Bero's argument that the FDA should be overhauled and run clinical studies itself, as happens with the equivalent agency in Italy:

"The Italian FDA collects money from every drug company that sells drugs in Italy, pools that, and funds drug trials. They fund the sort of head-to-head drug comparisons that companies don't like to fund. And they have independent people peer-reviewing the trials. It's a great model," [Lisa Bero] said."

A comment in response to Pure Pedantry, a blog by a PhD/MD student at Mount Sinai School of Medicine, also called for new ethical rules for the publication of drug company results.

Some of the other work that Lisa Bero and her colleagues have done to raise awareness about faulty reporting of clinical trials and conflicts of interest can be found in the Loxosceles science blog, which summarizes her talk at the ScienceWriters2008 meeting. This makes reference to a meta-analysis that shows that peer-review is not necessarily a guarantee against bias - a drug company funded study is four times more likely to turn up a result favorable to its own product than is an independent study.

This paper follows research published in PLoS Medicine in September by Ida Sim and colleagues that also investigated the publication status and publication bias of trials submitted to the FDA for a wide variety of approved drugs.

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NEJM opens online discussion on controversial study

Larry Peiperl — Mon, 24 Nov 2008 15:29:36 -0800

Earlier this month the editors of The New England Journal of Medicine invited readers to a more interactive role than we usually expect from a traditional medical journal. They offered us free access to a provocative clinical research article, welcomed us (paying subscribers or not) to read the accompanying editorial, and then, in a remarkable demonstration of the potential of open (or at least free) access, invited medical practitioners to comment in an online forum on the article: Will it change the way you practice? Why or why not?

Their offer received hundreds of thoughtful and articulate responses in the first two days, and many more over the following week. The paper, reporting on the JUPITER trial of rosuvastatin in participants with unremarkable LDL cholesterol levels and at least a moderately elevated high-sensitivity CRP, seems a particularly good choice. As a practicing internist as well as an editor, I can well appreciate the importance of identifying and treating apparently healthy patients whose normal LDL levels belie a high risk of heart attack or stroke.

Do the study results really tell us how best to help such patients? Many who made comments in the online survey were quick to raise insightful criticisms: the study did not enroll completely healthy people, but rather those with a variety of risk factors (such as metabolic syndrome and smoking) in significant proportions; there was no mention of appropriate non-pharmaceutical interventions (such as weight loss, diet, exercise, smoking cessation); the study drug was produced by the study sponsor and relatively expensive among statins; the treatment cost per case averted was in the hundreds of thousands of dollars; and so on. Should one change practice based on these results, screening widely for elevated CRP and prescribing rosuvastatin (or a less expensive congener) to those with higher levels? Interestingly, with a few days remaining to vote the tally appears to be running about even.

Many clinicians (myself included) would like to focus on the particular individuals most likely to benefit from an intervention, and conversely avoid unnecessary testing and treatment in patients where these might do more harm than good. The authors indicate that the relative risk reduction with treatment was approximately 50% over 2 years across the board: smokers, increased Framingham risk score, hypertension, metabolic syndrome, and so on. But the paper does not directly present the absolute rate of adverse outcomes in each risk group. Were the prevented events concentrated in, or perhaps largely limited to, those with risk factors that one could identify without routine testing of hsCRP?

Again as commenters have noted, the paper is not entirely clear about this point. Numbers of outcomes are said to be proportional to the size of the little black squares in figure 2, which I suppose one could measure and divide by the number of participants in each group to get risk estimates, but we’d still have to factor in the figure’s footnote that “data were missing for some participants in some subgroups.” The authors of an editorial in BMJ apparently did try to measure those little squares, and they comment that “A closer look at subgroup analyses (size of plots, exact numbers are not reported) indicates that most events occurred in high risk groups. Wouldn’t old fashioned risk estimation by traditional methods have produced similar results?” (Incidentally, if you live in the US and don’t happen to have a BMJ subscription, it will cost you $4.00 to read their critique. Not a huge amount, but if you’ve already been convinced by the article itself, that’s $4.00 further away from an hsCRP for yourself or a loved one. Is it worth the gamble?)

People who make patient care decisions clearly have a lot to say about high-profile papers with debatable results. As a clinician, I welcome this opportunity to see what my colleagues are thinking. That many of us are not deferring our decisions to industry-designated “thought leaders” bearing industry-approved slide presentations - nor yet to personable drug reps bearing pens and reprints - should come as no surprise. But to have the opportunity to have our say, right there on the NEJM site, the very source of those slides and reprints, is a new and important development. As an editor, I believe that the expectation of such public scrutiny could, over time, more sharply focus the design and reporting of clinical trials to address the specific questions that practitioners must consider in the interest of patient care. I’m looking forward to seeing how the comments will be incorporated into a permanently accessible record, and what relationship it will bear to NEJM’s “official” correspondence.

As clinician and editor, I applaud the editors of NEJM for providing this forum and hope it will become a regular feature.

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