DateTitlePlace 
30.11.-02.12.2016   6th General Assembly meeting       Lisbon, Portugal
 

 

June 2017

 

EMTICS cohort studies and database management

EMTICS is now entering its final phase, i.e. data analysis. The past 6 months have been dedicated to a very intensive and laborious data cleaning process which is now at its final act, thanks to the constant dedication of Andrea Dietrich and Pieter Hoekstra in UMCG, Groningen, Zachos Anastasiou, statistician working at the UCL site, and the Database team of the Istituto Superiore di Sanita’ (ISS) in Rome.
Over the past weeks this task force has been very active in obtaining an error-free statistical database, containing all clinical and laboratory data. They have been in contact with all clinical sites with regard to visit date/type inconsistencies.
Many thanks to all sites for their very helpful responses!
As a result of this effort:
•    314 visits that had not yet been closed have now been entered/closed;
•    167 visits with an incorrect visit date have been identified;
•    160 visits with incorrect type or visit numbering have been identified;
•    137 visits that needed to be deleted have been identified (as were erroneously entered fake visits).
It is really crucial that we now have correct visit dates as we aim to find longitudinal associations between infections and stressful events to the clinical course of symptoms over time (and then even one wrong visit date could ruin the analyses of a participant).
We are now also in the final stages of having a fully workable numerical output plus codebook. Furthermore we have coupled the lab data (all serum results, hair cortisol, DNA, RNA and throat swab results) to the correct visits, which will become part of the overall statistical database.
As next steps, we will again contact all clinical sites, this time to clarify improbable or missing clinical data entries (of which we have already identified quite a few). This is a very important part of the cleaning as we obviously need to have correct and complete values for the clinical ratings (including the core ratings of tic, ADHD and OCD severity) as we aim to relate these to the various lab results.
As a final update we are pleased to mention that Andrea has been co-ordinating the entries of the weekly diaries of all participants. This is allows us to obtain many more time-points of tic severity fluctuations than we have been able to identify through the visits.
At the current stage of follow-up (mean duration 1.35 years), 260 participants have been recruited in ONSET, and 55 of these 260 (21%) manifested a new onset of tics. In the COURSE study, 716 patients were enrolled and have been followed up to date for a mean duration of 1.07 years; 181 (25%) underwent at least one clinically relevant exacerbation, for a total number of 213 exacerbations of tics from the whole cohort.

Immunological studies in EMTICS
The analysis of immune markers from serum and whole blood of cohort participants is a key component of the EMTICS study, managed by our LMU partners. The analyses focusing on the adaptive cellular immune response have been finalized. Serum sample testing has been completed with respect to streptococcal serology, cytokines and soluble immune factors, as well as monomeric and pentameric C-reactive protein. Analyses of anti-neuronal antibodies are ongoing. Serological assays for different non-streptococcal pathogens and tryptophan pathway intermediates have been established and will be conducted in the last trimester of 2017.

Exploring psychosocial stress
Workpackage 8 of EMTICS investigates the influence of stress on the tic fluctuations. At the present stage the TU Dresden group continues its analyses of cortisol in hair samples of all patients. The analyses will be completed at the end of July 2017. In addition to questionnaires, reports and observations, this biomarker is important for estimating the influence of psychosocial stress on tic severity. Therefore the results will be included in the database at the end of July. Furthermore, some analyses of hair samples from mice investigated at the Istituto Superiore di Sanita’ (ISS) in Rome have been conducted (see next paragraph).

Animal model studies
These studies have been conducted at the Istituto Superiore di Sanita’ (ISS) in Rome. The studies conducted in previous years showed that repeated exposure to GAS injections resulted in behavioural and neurochemical alterations isomorphic to TS/PANDAS symptoms. In previous studies our partners also demonstrated that neonatal exposure to corticosterone (an experimental paradigm to mimic neonatal stress) compensated for most of the identified abnormalities.
An independent study was performed to investigate whether exposure to social stress during development (i.e. at the same time in which mice were exposed to GAS administration) modulated the TS-like phenotype in a different way compared to neonatal exposure to stress. Social stress was operationalised through the presence of an aggressive mouse in the same cage in which the focal mouse was housed: although mice were constantly in visual contact, physical interaction was limited to a maximum of 10 minutes per day. In this study our partners replicated the finding that GAS exposure induces alterations in phenotypes isomorphic to TS symptoms. Exposure to social stress altered the individual phenotype independently of GAS administration. However, exposure to social stress neither normalised nor deteriorated the GAS-dependent phenotype.
Blood and brain samples from these mice will be investigated through immunological and neurochemical analyses.


We are all looking forward to the crucial work that will be undertaken in the next months and to the final general assembly that will take place in Mallorca (May 2018)!

 

Here you can find our

Our Grant Agreement and Art. II.30.4 / II.12.2 of our grant agreement lay down the following rules:

  • The following standard disclaimer and acknowledgement is to be written on all publications of EMTICS:

„The project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 278367.

This paper reflects only the author’s views and the European Union is not liable for any use that may be made of the information contained therein.”

This means for you: Do not forget to include this information in your manuscripts or on your posters or books. It is a contractual duty!

  • Any dissemination activity shall be reported in the plan for the use and dissemination of foreground, including sufficient details/references to enable the Commission to trace the activity.

This means for you: Please keep track of your publications as they need to be reported on in the frame of our periodic reports.

  • With regard to scientific publications relating to foreground published before or after the final report, such details/references and an abstract of the publication must be provided to the Commission at the latest two months following publication. Furthermore, an electronic copy of the published version or the final manuscript accepted for publication shall also be provided to the Commission at the same time for the purpose set out in Article II.12.2 if this does not infringe any rights of third parties.

This means for you: Please send an abstract of your publication to the project office at concentris the moment when it is accepted for publication. concentris will forward it to the relevant services at the EC for you.

  • According to Special Clause 39 of our grant agreement, we are furthermore bound to the following provisions:

In addition to Article II.30.4, beneficiaries shall deposit an electronic copy of the published version or the final manuscript accepted for publication of a scientific publication relating to foreground published before or after the final report in an institutional or subject-based repository at the moment of publication.

Beneficiaries are required to make their best efforts to ensure that this electronic copy becomes freely and electronically available to anyone through this repository:

  • immediately if the scientific publication is published "open access", i.e. if an electronic version is also available free of charge via the publisher, or
  • within 6 months of publication.


In addition to this, the EMTICS Consortium Agreement contains the following provisions:

  • 8.4.1 Publications

Dissemination activities including but not restricted to publications and presentations shall be governed by the procedure of Article II.30.3 of the EC-GA subject to the following provisions.

(1) Prior notice of any planned publication shall be made 45 days before the publication. Any objection to the planned publication shall be made in accordance with the EC-GA in writing to the Coordinator and to any Party concerned within 30 days after receipt of the notice. If no objection is made within the time limit stated above, the publication is permitted.

(2) An objection is justified if

  • the objecting Party's legitimate academic or commercial interests are compromised by the publication; or
  • the protection of the objecting Party's Foreground or Background is adversely affected.

The objection has to include a precise request for necessary modifications.

(3) If an objection has been raised the involved Parties shall discuss how to overcome the justified grounds for the objection on a timely basis (for example by amendment to the planned publication and/or by protecting information before publication) and the objecting Party shall not unreasonably continue the opposition if appropriate actions are performed following the discussion.

This means for you: Please send any manuscript resulting from EMTICS work to the Consortium before publishing it. The Consortium members may object within 30 days.

  • 8.4.2 Publication of another Party’s Foreground or Background

For the avoidance of doubt, a Party shall not publish Foreground or Background of another Party, even if such Foreground or Background is amalgamated with the Party’s Foreground, without the other Party’s prior written approval, which shall not be unreasonably withheld. If the other Party has not raised an objection within 30 (thirty) calendar days after receiving the manuscript, consent to the publication is deemed to be granted.

The following was agreed by the EMTICS Consortium at the Kick-off Meeting in AMSTERDAM:

  • The whole consortium is last author through “the EMTICS consortium”
  • The data base is open to all for publication proposals; the Coordinator will draft and circulate a proposal about publication topic divisions and more detailed publication rules
  • *The group felt that the 45 days until green light of a manuscript for submission is too long in practice. The group agreed on 2 weeks for comments.
  • All centres to send information to the project office (Dr. Sara Stöber) on who is part of the EMTICS consortium from their centre (standard). Of course, people can withdraw from authorship for publications on a case by case basis.

European Multicentre Tics in Children Studies: translating pre-clinical results into therapies



EMTICS aims to identify the genetic and environmental susceptibility factors of tic disorders and will greatly contribute to a better understanding of the underlying mechanisms, especially by elucidating the role of autoimmunity and infections. EMTICS is a project funded by the EU programme FP7 and combines 27 partners from 11 different countries.

Read more

Tic disorders

Tics are characterised by the presence of multiple sudden, rapid, recurrent, and non-rhythmic movements and/or utterances.

About EMTICS

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Aims of study

EMTICS wants to elucidate the causes of tics in children and to find an effective treatment for the disorder.

About EMTICS

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