From Academia to the Authorities

Let's start with the basics. My name is Henriette, I am 28 years old and I will soon be an alumna from the MedNeuro MSc and PhD programs at the Charité. 

I started my PhD in 2014 in the group "Experimental Psychiatry" with Prof. Christine Winter. My focus revolved around neuropsychiatric disorders and my daily work contained a mix of performing stereotactic surgeries, behavioral experiments and electrophysiological recordings. My thesis is written and ready to go, the plan is to open the procedure this summer.
However, a lot has happened since I finished lab work in 2017. I moved back to Denmark, mainly with the purpose of getting closer to my family (I am a dane) and finding a job. Luckily, all of this fell into place rather quickly.

Henriette Edemann Callesen

I started looking for jobs a few months before moving back to Denmark. I spent a lot of time figuring out what kind of job I wanted, which wasn’t easy. Moving from research into the “real world" seemed rather daunting. I mainly saw myself as a researcher and was interested in continuing in this field. Yet, after almost three years of working with rats, I wanted to get out of the lab. I did quite a lot of soul searching to figure out what kind of position met my requirements and to understand what qualifications the PhD had given me. In this period, I even wrote an article in the CNS newsletter about this topic – simply because I had to put my own doubts into words and let go of the imposter syndrome.

Let go of the imposter syndrome

I eventually boiled all my qualifications down to a proper CV that included my PhD, but also some organizational work I had been doing on the side. I made sure that the focus was not on my published papers nor my everyday handling with rats, since this is only relevant if you want to stay in academia. Back in Denmark, I sent out a bunch of applications. To make the story short: I am now an Academic Employee at the Danish Health Authorities in Copenhagen.

My Work Has Clinical Impact
My daily work evolves around constructing National Clinical Guidelines. I attend meetings with clinicians to figure out where the problems in their daily work are. For example, we discuss whether there is lack of evidence for the treatments that are being applied, or if one treatment is better than another. Then I go through research publications, critically evaluating its quality (using the so-called GRADE method [1]) in order to find out more about the effects of different treatment options. All of this is then composed into a National Clinical Guideline, which physicians can use in their daily work when doubt arises.

Use your qualifications wisely

And, boy, is this work different from being in the lab! I no longer work with rats, I have normal working hours and I get to drink coffee at my desk, while going through research. I developed competencies in understanding what contains good research (and what not) and I get insight into the challenges doctors face daily. Moreover, my products have clinical impact, which is very motivating.
What I miss, though, is being able to sit down and scientifically analyze and interpret data. I miss the flexibility that comes with being a PhD student, including structuring the day myself. I miss my friends and colleagues in Berlin and the thrill of being abroad. With that said, right now, I would not change it for the world. My new position offers other interesting possibilities and I get to grow in a different direction then what I would have if I had stayed in academia.
So, to all of you currently in academia who are thinking about changing tracks: first of all, yes, your PhD is a valuable asset that can land you a job in the “real world”. However, be aware that when promoting yourself, employers outside academia value other aspects of your work than a potential PI. There are indeed jobs out there, where you can combine research and regular working hours. Seriously, let go of the imposter syndrome that many PhD students have. Use your qualifications wisely, take a leap and go for it.

by Henriette Edemann Callesen, MSc and PhD Alumna, MedNeuro


[1] http://bit.ly/1IQ69Ub

This article originally appeared March 2018, in Beauty and the Brain , Vol 11 - Issue 01

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

The DESIRE Project for Epilepsy: Is Collaboration in Science More Efficient Than Competition?

700 million people will have a seizure in their life - that means 1 out 10 human beings. Epilepsy, which can only be diagnosed after a minimum of two seizures (more than 24h apart) is the third most common neurological condition in the European Union following Alzheimer’s disease and stroke.

Despite these facts, the disease is still widely misunderstood and often stigmatizing.  On September 15th 2011, a new piece of legislation entitled the EU Written Declaration on Epilepsy was approved by the European Parliament after being signed by a strong majority of 459 members (out of 751) [1]. The Declaration initiated a change in the funding strategies of the EU: new funds were allocated, and several research projects were created. Today, the EU is handing out 173 million euros that fund a dozen or so European research projects [2]. Among them: the DESIRE project [3].

Epilepsy : a Misunderstood Disease
This enticing acronym stands for “Development and Epilepsy - Strategies for Innovative Research to Improve Diagnosis, Prevention and Treatment in Children with Difficult-to-Treat Epilepsy”. Now that I’m re-reading this I do not think it’s an acronym- if you take the initials of all important words, then remove half of them, you’ll get „DESIRE“. Anyway, the important words here are “children”, and “hard to treat epilepsy”. Epilepsy can hijack the life of people of all ages and it can have many causes [4]. DESIRE focuses on abnormal early (intrauterine) development of the cerebral cortex and its association with epilepsy [4,5]. During neurodevelopment, precursor cells formed in the periventricular region migrate to their correct location where synapses are made and later edited to produce a mature brain. Any interruption of these processes can create cortical abnormalities [5-7]. Most of these malformations have genetic underpinnings, however, environmental factors such as lack of oxygen or intrauterine infection also play a role [4]. These types of epilepsy are difficult to treat because the underlying pathology varies substantially and patients often have severe comorbidities. 

'DESIRE'  FUNDS MORE THAN 250 RESEARCHERS FROM 11 COUNTRIES

The DESIRE project funds the research activities of more than 250 researchers from 25 universities in 11 countries [3]. Since the Charité is one of the partners and DESIRE funds my PhD, I have attended the last four yearly meetings of the project. The last one was in Valetta (Malta) mid-october. I know what you’re wondering and yes, the weather in Malta is beautiful this time of the year. More seriously, it has been fascinating to see the projects evolve over the years. Researchers don't necessarily need a big European project to collaborate and exchange information, but I have personally never seen cooperation between researchers on this scale before.

DESIRE Leads to Scientific Collaboration
Let me explain. One of the eight work packages within the DESIRE project aims to “Identify genetic causes and pathomechanisms of epileptogenic brain malformations”. The first step is to pin down germinal or somatic mutations in patients with a specific type of malformation. Once you have identified a new interesting mutation in a patient you need at least one more patient to be able to claim a possible causality. Since these malformations are extremely rare this can be nearly impossible. In 2014, during the first meeting that I attended, 20-30 researchers and group leaders sat around a table and started exchanging genetic mutations. The amount of information exchanged in one afternoon was overwhelming. In the following years, databanks were created, pools of interesting genes were selected, and samples were sent across Europe to be systematically tested. Today, 150 patients with malformations of the cortical development and 450 with encephalopathies have been included in the project. This led to the identification or confirmation of several mutations (notably in the PIK3/mTOR pathway and in different types of voltage gated sodium channels) [8-10]. In the meantime, samples were analysed in Erlangen (DE) and a pattern of methylation in a specific type of malformation was identified. Epigenetics were previously known to have a role in epilepsy [11] but this was a breakthrough.

Once a mutation is identified, it needs to be tested. Using in-utero electroporation, these mutated gene sequences were introduced into mice, rat, or ferret embryos to create better models for cortical malformations (the latter is a good model for cortical development because it is convoluted like higher mammals [12]). In many cases, the models showed malformations comparable to those observed in patients, and the pathomechanisms could be studied [7], [13].
Every meeting is extremely dense, each member presents the advancement of their project within their work package, even negative results, often before they are published. There is a sense of community; even competitive teams exchange tips and comment on each other’s data. DESIRE ends in September 2018 and it will certainly meet most of the objectives set in 2013. One of the concluding remarks in Malta by Prof Jeffrey L. Noebels member of the Scientific Advisory Committee was that the most impressive work had been done by collaborations between teams within DESIRE. Let us hope this spirit of collaboration will continue on after the end of DESIRE.

by Aliénor Ragot, PhD student AG Holtkamp
This article originally appeared December 2017 in CNS Volume 10, Issue 04, Sleep 

[1] http://bit.ly/2zfet2n/ 
[2] http://bit.ly/2yAAqaU
[3] http://bit.ly/2Am5jBq
[4] http://bit.ly/1wgpTup
[5] Romero DM, Semin Cell Dev Biol, 2017
[6] Fernandez V, EMBO J, 2016
[7] Khalaf-Nazzal R, Hum Mol Genet,2017
[8] Alcantara D, Brain, 2017
[9] Parrini E, Hum Mutation, 2017
[10] Møller RS, Neurol Genet, 2016
[11] Kobow K, Neurosci Lett,2017
[12] Neal J, J Anat, 2007 
[13] Martinez-Martinez MA, Nat Commun, 2016