New Issue Out Now: BRAIN INVASION

The brain is an amazing thing: it allows to think, feel, create and do lots of other less-glamorous things like breathe and digest your lunch. But what's even more amazing is the system that our body has involved to keep it that way. This issue of the newsletter is all about how things can find their way inside our heads- for better or for worse!

 

https://bit.ly/2LwCVRU

First off, have a look at our primer on the different ways in, intracortical implants to poorly cooked food (page 3), and learn more about the body's first line of defense (page 7-8). We also have a first-hand account of a particularly sneaky invader (page 4), as well as clinical reports of foreign objects turning up where they definitely shouldn't be (page 9)! But it's not all bad news! Recent developments have meant that our senses can be augmented (or even repaired, pages 5 and 10), and optogenetics has "illuminated" a whole new realm of experimental possibilities (page 13-14). Are we ready for blending our brains and technology? We have two stories examining the ways authors play with the idea of cyborgs (pages 11-12), as well as providing some thought-provoking watching material (page 7).
Of course, we also have stories from the here and now on campus. What's the point of publishing negative results (page 19)? Are MSc students treated fairly (page 18)? What is it like to work for a big pharma company (page 16)? And, most importantly: what the heck is going on with those yellow buses all over campus (page 21)?

Happy reading, dear readers! We hope that this issue will stick in your head.

Constance Holman and Claudia Willmes
Editors-in-Chief

Book Review: Bad Science

A Book by Ben Goldacre, a man who signed his dead cat up as a certified professional member of the American Association of Nutritional Consultants to prove a point.

"Let me tell you how bad things have become" begins Bad Science, before describing the Brain Gym exercises currently practiced in British schools. If you, as a budding neuroscientist (or even just as a sane individual), are concerned by the idea of children being taught that nodding their heads vigorously will make them smarter by increasing blood flow to the frontal lobes then you might want to read on. Ben Goldacre, a British doctor, is on a crusade and this book outlines his manifesto. He targets three main audiences and carries them on a crash course through modern science, mainstream media and money-making 'medical' quackery. Goldacre writes for us - scientists - as well as reaching out to people with no scientific education and imploring his 'enemies' - scare-mongering journalists and greedy nutritionists - to see reason.

Book cover of "Bad Science"

The book outlines a clear set of ideas about the advancement of public knowledge of science and Goldacre explains the obstacles he sees to these goals through a series of succinct examples of media debacles and blatant false advertising. Bad Science is the art of misinterpreting statistics, underestimating placebo effects and taking advantage of health worries and scientific ignorance in the general public to make a quick buck. Most of this is explained whilst maintaining a humorous tone - if you like gathering fun facts about the reality of recreational drug use or finding out the truth about 'Horny Goat Weed' aphrodisiacs then this is your book - but he also describes a darker side: the people who don't want to stop making money from dodgy therapies. One chapter is only included in the most recent edition of the book as Goldacre was being sued for libel by its subject, a multivitamin-pill magnate peddling lies in AIDS-striken South Africa.

Check out his TED talk!

As a population with at least basic knowledge of the procedures of evidence-based medicine, we medical neuroscientists may end up feeling a little smug as Goldacre dips into statistics and scientific reasoning. Despite this, for me at least, it served as a necessary reminder that one must always seek the full story beneath anything from a peer-reviewed academic paper to a sensationalised tabloid newspaper article. Although probably preaching to the converted, Goldacre's closing plea to scientists to make sure our work is known and not misinterpreted is sound advice. This book will make you reassess the way you think about science in the media. Please read it (or at least watch his TEDtalk).



by Ellie Rea

this article originally appeared March 2012 in Volume 5, Issue1, "Mental Health Disorders"

Journal of Negative Results in BioMedicine

The Journal of Negative Results in BioMedicine is an open access journal publishing negative data sets, that encourage discussions on ambiguous, unanticipated or provocative results with regard to currently accepted concepts. 
Thereby, the journal wants to challenge present scientific models and dogmas. In particular, the publication of work demonstrating that standard methods and techniques are sometimes inapplicable to some studies is of a great advantage to other researchers in their respective fields. Also, scientists and physicians are invited to publish clinical trials that do not show a higher efficacy in therapy than current treatments. This can eventually lead to the improvement of experimental design and treatment strategies.
As traditional journals infrequently publish negative studies, valuable information often becomes inaccessible to other researchers to evaluate and analyze. In particular, negative or controversial results contradicting prevalent theories aren't easily published - although they might be innovative.
Of course, not all null results and controversial data would necessarily be groundbreaking. In short, the journal believes that the publication of such results is an important influence on the scientific community to consider and improvise upon in their own research.

Check this out: http://www.jnrbm.com/

by Nicole Hentschel
This article originally appeared on June 1, 2011 in  Volume 4 - Issue 2, "Good Scientific Practice"

The Journal of Unsolved Questions (JUnQ)

PhD students from the Graduate school of Material Science (MAINZ) launched a scientific journal to publish negative results.
In the journal of Unsolved Questions (JUnQ), scientific projects gain interest that would never be published in traditional scientific journals: those with negative or inconclusive results. As most of the research projects fail to show positive results with clear conclusions, many results are not published. Accordingly, a lot of information is not available to the scientific community and gets lost.
This Journal provides a platform to exchange data on projects which did not work and are unfinished. Thereby, JUnQ wants to establish the publication of negative results as an important milestone for scientific communication especially among different disciplines to overcome biases and fraud. In addition to these articles, JUnQ also publishes short essays about open scientific questions which have not been solved yet but are important to the science community. According to good scientific practice, the articles are peer-reviewed by independent referees of the respective scientific field. Furthermore, the essays about open questions will be broadly reviewed in order to only publish scientific questions that do not contain false facts.

PUBLICATION OF NEGATIVE DATA AS AN IMPORTANT MILESTONE

Beyond that, JunQ wants to reflect about the day-to-day business in science from a meta-perspective. This will be achieved through different formats. Thus, this summer semester, JUnQ organized a lecture series with the topic "Publish or Perish...?" which discusses the influence of prevalent publication practices in natural sciences.
The first issue of JUnQ was published on January,1^st, 2011 and contained two articles and 4 open questions. To get a copy and more information about JUnQ, go to http://junq.info. Articles and Open Questions can be submitted to JUnQ@uni-mainz.de.

by Nicole Hentschel
This article originally appeared on June 1, 2011 in  Volume 4 - Issue 2, "Good Scientific Practice"

Of the Importance to Publish Negative Results

I had a rough time during my PhD with many experiments that did not support a common hypothesis in my field of research. However, I was able to successfully submit a manuscript describing my negative data. Recently I even won a prize for publishing them.

When scientists embark on a new study, they formulate a hypothesis that they want to test. Sometimes the experiments do not support the hypothesis the researchers set out to test. If the obtained data are unable to confirm a hypothesis or replicate previous results, they are called negative results. Sometimes they are also called NULL results, as the Null hypothesis H₀ (the hypothesis that there will be no difference between experimental and control group) was not rejected. Most of the time, negative results are more accurate and give more informative than results that support a new hypothesis. 

If a test of experimental data comes up significant with p < 0.05, we reject H₀ and accept H₁ (the hypothesis that the results show an effect). Notably, we only tested H₀ and the p-value says nothing about the probability of H₁ being true. However, a non-significant p-value means that H₀ is true (or the data didn’t have enough power to reject it). In a Bayesian sense, data underlying a non-significant p-value can be strong evidence for the H₀. 

Negative data are obviously not very spectacular, because we want to find out what is true, not what isn’t. Positive results seem more interesting and more important than NULL results. The latter are often not submitted for publication, because they are believed to generate less value to scientists and academic publishers. Indeed, they are less likely to open new avenues of research that generate funding opportunities. Manuscripts reporting negative data are also more likely to get rejected, because they appear less exciting. Traditionally it is difficult to publish negative data, unless they refute a spectacular claim. Studies that do not confirm a new hypothesis often get literally filed away in a drawer. Therefore this is also called the “file drawer phenomenon”.

PUBLISH ALL RESULTS TO FIGHT THE PUBLICATION BIAS! 

Unfortunately, the negative data get lost to the scientific community. If ever another group of researchers has a similar hypothesis, they are likely to tap into the same dead end. The fact that such negative data are rarely published, leads other scientists to waste time and effort by unnecessarily repeating experiments. It is estimated [1] that this costs the US economy alone, $28bn each year, similar in scale to the total $35bn National Institute of Health annual budget [2]. Moreover, the bias towards positive results can lead to an overestimation of biological phenomena or efficacy of drugs. It is devastating and frustrating, if the biased representation of preclinical work compromises the outcome of drug trials. Thus, publishing more negative results will have a positive impact on the development of new drugs and healthcare solutions. 

by Maklay 62 via pixabay

Another current problem is reproducibility. Even though it is fundamental to scientific progress, replication of studies carries little prestige in academic research. Especially in neuroscience, reproducibility has come under particular focus due to some spectacular cases, where data could not be reproduced [3]. Recently, systematic studies demonstrated that current biomedicine has a serious replication problem. It is shocking that more than half of the published biomedical data could not be reproduced [1]. This led to the declaration of a reproducibility crisis. It is necessary to value the effort to reproduce and publish studies regardless of their outcome.

 SCIENCE IS MOST EFFECTIVE WHEN BOTH POSITIVE AND NEGATIVE RESULTS ARE PUBLISHED

Fortunately, many journals now publish reproduction studies and negative data; for example PeerJ, PlosONE, J Neg Res Biomed, Scientific reports and others. Furthermore the necessity to reproduce experiments and publish negative results gets now also recognized by funding agencies that award publications that do not confirm the expected outcome or original hypothesis. The prizes aim to emphasize the value in publishing all the results, as science is most effective when both positive and negative results are published. Another way to fight publication bias and focus on the scientific process and soundness are “Registered Reports”. For this type of journal article, methods and proposed analyses are pre-registered prior to research being conducted. Thereby the results are accepted for publication before data collection commences and without regard to their positive or negative outcome.  
These efforts show, that the recognition to publish negative results and replication studies is growing. Hopefully this will contribute to the soundness of science and retrieve research from the reproducibility crisis.

QUEST is giving away 15 awards of € 1,000  to first/last/corresponding authors (BIH, MDC or Charité affiliation) of preclinical or clinical research papers in which the main result is a NULL or ‘negative’ or in which the replication of own results or the results of others is attempted. Futher information can be found here.

The ECNP’s Preclinical Data Forum created the “ECNP Preclinical Network Data Prize”, a prize for published “negative” scientific results, of €10,000. Aimed initially at neuroscience research, it encourages publication of data where the results do not confirm the expected outcome or original hypothesis. The ECNP’s Preclinical Data Forum is a mixed industry and academic group which aims to improve the replicability and reliability of scientific data, especially in drug development. Futher information can be found here.

by Claudia Willmes, PhD Alumna AG Eickholt / AG Schmitz  

[1] sciencemag, 2015 http://bit.ly/2E5ho01
[2  sciencemag, 2017 http://bit.ly/2uWuFTt
[3] nature news, 2014 http://go.nature.com/2rAME4b

Piracy Ahoy: Hackers Get (Neuro)scientific

Working at a large, wealthy institution like the Charité, we are mostly insulated from the frustrations of academic paywalls. Multi-million euro academic subscription fees assure that works published in most large biomedical databases are easily within reach, and not being able to access a publication is the exception. However, in other places, a publisher paywall can literally make or break an academic career. A single paper typically costs around 20-30 euros to purchase, while some websites cheekily offer “rentals”. Imagine yourself considering what you can afford to read. In science, information is power, and corralling this information behind paywalls means a steep imbalance in who gets to set the tone of the cutting-edge research.

Introducing Sci-Hub
If the digitization of scientific knowledge is feeding an ever-growing problem, could it also provide some solutions? Some self-proclaimed scientific data pirates are using big data to beat online scientific publishing at its own game. Enter Sci-Hub [1], the “Pirate Bay of Scientific Publishing”. On this site, not unlike PubMed, anyone can search and download texts pertaining to their scientific field. It’s free, simple, and incredibly popular worldwide. Understandably, the publishers hate it.
A few quick facts and figures [2]: Sci-Hub handles about 200,000 paper requests per day, coming from all over the world and most academic disciplines. The heaviest use of the site is in Iran, but other nations aren’t far behind. The publisher arguably being hit hardest by these illegal downloads is Elsevier, though analysis found that Sci-Hub was only diverting about 5% of its legal traffic. Thus far, more than 6 million papers have been accessed through the site, and these numbers continue to grow. The number one downloaded paper so far was a piece on wind turbine testing [3], followed by a paper on glioma [4].
Sci-Hub was the brainchild of 22-year old Kazakh computer science and neuroscience student Alexandra Elbakyan. Frustrated by the lack of availability of scientific resources in her home country and with a knack for hacking, she created the site in the hopes of leveling the playing field for academics worldwide [5]. She’s widely been celebrated as a game-changer in the field of digital media, but her whereabouts are currently unknown… Due to ongoing legal proceedings, being found could mean imprisonment.

via Wikimedia Commons

The Publishers Strike Back
In 2015, the publication group Elsevier sued the website for unlawful use of copyrighted material [1]. Despite Elbakyan invoking the Universal Declaration of Human Rights, which calls on signatory parties to "to share in scientific advancement and its benefits", Sci-Hub lost, and the website was promptly taken down. However, thanks to a sophisticated team of hackers and administrators involved in the project, it was up again in no time, and has since appeared under several different domain names. In the age of Big Data, Sci-Hub is not disappearing anytime soon.
Recently, Science magazine undertook an official study on the use of Sci-Hub, and the results were surprising. Whereas the study authors expected that use of the site would be most popular in less developed countries, it seems that the site was also being heavily used in Europe and North America [2]. Site critics seized on this point, claiming that for most, data piracy was an issue of convenience, rather than necessity. In some sense, they’re right: Science’s analysis of the site found that a large number of open-access articles (which theoretically anyone, anywhere can access) were being pulled from the site.

Leverage and Loopholes
There are other reasons why some are skeptical of Sci-Hub. One argument is that official publishers often keep track of downloads and usage statistics for individual works – something that Sci-Hub doesn't do. These statistics are increasingly being used as career metrics for researchers. Without facts and figures about journal readership/downloads, institutions or smaller publishers may cut ties with periodicals that are immensely popular and useful to the community [6].
A final argument from the publishing industry is that many large companies already have lots of ways to get free access to articles in their collections. For example, after users register with the journal Science, they can access all articles that were published more than a year ago for free [6]. However, not all journals are as generous with their materials, and the loopholes that researchers have to jump through make the process cumbersome, and still occasionally expensive. The heavy use of Sci-Hub in less wealthy countries suggests that (a) most researchers don’t know about these special channels to access manuscripts behind paywalls, or (b) they don’t work as advertised [2,6]. Whether a matter of education or logistics, it’s clear that there is still significant work to be done on the part of the journals.

Piracy or Cooperative Change?
However, one point remains a fact: publishing companies are not immune to change. Ten years ago, open access publishing for scientific articles was still in its infancy, and today represents a major step forward in the democratization of scientific knowledge. This happened through public pressure together with cooperation of the companies. But will publishing companies ever be able to deal with scientific data piracy in a productive manner? Peter Suber from the Office of Scholarly Communications at Harvard put it succinctly when interviewed in Science: “Lawful open access forces publishers to adapt […], unlawful open access invites them to sue instead.” [2].

by Constance Holman, PhD Student AG Schmitz


[1] http://bit.ly/1UI574H
[2] http://bit.ly/1STnFAv
[3] Osgood et al. Proceedings of the IMAC-XXVIII, 2010
[4] Cancer Genome Atlas Research Network, NEJM 2015
[5] http://bit.ly/1SIgci8
[6] http://bit.ly/1NO7qSS

ENCODS 2016: An Insight Into the Publishing Process

ENCODS 2017 will also offer a number of workshops. One of our students attended the "Publishing Process" workshop last year:

The ENCODS 2016 program contained inspiring keynote lectures from various neuroscience fields, interesting talks by PhD students, lunch poster sessions, various workshops to choose from and offered, last but not least, a great opportunity to meet fellow students from 35 different countries. 

Publishing in a Top Journal
An especially interesting part of the program was the workshop “The Publishing Process” held by Alexander Arguello, Associate Editor of Nature Neuroscience. He gave us a professional insight into the processes of publishing and editing and was ready to discuss associated problems. He opened the workshop with a brief history of scientific publication and then explained the editing process at Nature Neuroscience, which is coordinated by eight editors. They receive and evaluate altogether about 250 papers per month and decide on rejection or review – at the end of this process, approximately 10% of the submitted articles are accepted. Besides considering the interest of the article for the typical reader of the journal, the assessment is mainly based on the abstract, focusing on clarity, novelty, scientific benefit and a plausible concept of the study. 

Good data visualization is key

Considerable focus is also placed on graphs and pictures, which should clearly convey the message of the paper without needing the actual text – nice images are always a plus! In the end, each editor alone, sometimes after consultation with his or her colleagues, has the final say on whether a paper goes into review or is sent back to the author. We concluded this part of the workshop by evaluating various abstracts that had actually once been sent to Nature Neuroscience for their chance to be published. This was not always easy to do at first glance!

Do We Still Need Printed Journals?
During the course of the workshop, we also discussed the problems and advantages of printed journals versus open access options. As more and more papers are published every year, it is hard and time-consuming to decide which articles are worth reading, especially if they are outside one's own research focus. Printed journals can serve as a “filter” and provide a selection of important articles. However, as they are intended to reach a broader audience (and pursue financial interests), they tend to follow certain trends, as is currently happening with the Zika virus or CRISPR. Moreover, especially widely read journals such as Nature do not always succeed in identifying revolutionary, paradigm-shifting ideas. In fact, those are often published in smaller journals – so don’t feel bad if your paper doesn’t make it into Nature!

 Printed journals tend to follow fads

The majority of the workshop participants were in favor of open access publishing, as it seems to make scientific results more transparent and can provide a platform for constructive discussion. Nonetheless, there is a certain danger of false data interpretation that might lead to a misunderstanding of scientific results by non-experts. A solution to this problem might be a database only open to experts from a particular field of science. 

Scientific Journal Editor As a Job Option
For those who are still undecided whether or not to stay in research after finishing their PhD, it might be worthwhile to know that being an editor in a scientific journal is actually a realistic job option. The work as an editor at Nature Neuroscience consists not only of the above mentioned tasks, but also of travelling to various conferences to keep up with the latest developments in science. So, if you are looking for a job without all the worries about grants, funding and temporary contracts this might be a career option for you. Just go to the website of your favourite journal to check for open positions!

by Anna Pfeffer, PhD Student AG Steiner
This article originally appeared in September 2016 in "Happy Anniversary MedNeuro"