PHD DAY

PHD DAY

ABSTRACTS

22 JANUARY 2021

HEALTH

8.20 Welcome and presentation of programme

Fabio Renato Manzolli Leite, Associate professor, Department of Dentistry and Oral Health, Aarhus University

Welcome by the chair of the PhD Association

Maria Louise Gamborg, PhD student, Chair of the PhD Association at Health, Aarhus University 8.30 Keynote lecture "Put your talents into play and make a sustainable career” by Malene Hein,

COO of Play you Talent

Introduced by Fabio Renato Manzolli Leite, Associate professor, Department of Dentistry and Oral Health, Aarhus University

9.30 Presentation of “how to behave at an online conference”

By Peter Musaeus, Associate professor, Centre for Educational Development, Aarhus University 9.50 Break

10.00 Flash talk presentations 11.35 Break

11.45 Poster presentations 12:55 Break

13.05 Fogh-Nielsen Competition

Chaired by Søren Moestrup, Professor, Chair of the Fogh Nielsen Board and Pernille Louise Kjeldsen, PhD student, Department of Clinical Medicine, Aarhus University

13.50 Break

14:00 Oral presentations

15:30 The JCD, the 3R and the Fogh Nielsen award ceremony 16:05 Closing remarks

Helene Nørrelund, Head of the Graduate School of Health, Aarhus University 16.10 Break

16:30 Simon Talbot tailored comedy quiz 17:10 Programme of the day ends

PHD DAY 2021 PROGRAMME

22 JANUARY 2021

1

Aarhus University

Graduate School of Health

PHD DAY

22 JANUARY 2021

PhD Day 2021

On behalf of the PhD Association, the Graduate School of Health, Aarhus University and this year’s Organizing Committee, we welcome all students, faculty members and distinguished guests to the PhD Day 2021.

The day is a celebration of the PhD students and other students at Health and their research contribution. Changes to the structure of the day, will give you a chance to witness more of your colleagues’ presentations. We hope you will seize this opportunity and expand your ideas by joining the sessions on Zoom.

Though the set-up of this year’s PhD day is different from previous years, the day is as always, a chance for you to present your research to your peers as well as to more experienced researchers, and for you to act as co-chair, giving you the opportunity to get experience with acting as a scientific panel member in a conference.

This year, we are proud to present Malene Hein, Chief Operating Officer (COO) of Play Your Talent, as the keynote speaker. Under the title “Put your talents into play and make a sustainable career”, she will inspire you on how to discover and cultivate your talent. When we are aware of our talents, we can select our career path smarter and match it to our passion and drive; as a result, we increase our motivation and work joy by 30%. Success is not something we get; it is something we create ourselves.

Since the day takes place online, Peter Musaeus, Associate Professor at the Centre for Educational Development at Aarhus University, will share his insights on “how to behave at an online conference”

and prepare you for presenting and participating in the online sessions.

Remember to stay online at the end of the day. Not only do we have the JCD, the 3R and Fogh Nielsen prize award ceremony, we also conclude the day with the “Simon Talbot tailored comedy quiz”. Simon Talbot is a renowned Danish stand-up comedian, and at the PhD Day, he will mix stand- up, sketches and a quiz with prizes tailored just for us (all in English). So join your peers and colleagues online for a fun conclusion of the PhD Day 2021.

A warm thank you to everybody who participates on the day and to those that has helped create a highly scientific and inspiring programme.

Fabio Renato Manzolli Leite, Associate professor Chair of the Organizing Committee

Health, Aarhus University

Jacob Thyrsted Jensen, PhD student Co-chair of the Organizing Committee Health, Aarhus University

Helene Nørrelund , Head of Graduate School Health, Aarhus University

Maria Louise Gamborg, PhD student Chair of the PhD Association

Health, Aarhus University

Keynote speaker

Malene Hein, COO, Play Your Talent

As a Strategic partner and Lecturer, Malene is an expert in facilitating sustainable change management processes. During the last five years, she has created continual transformations for leaders and teams, which are noticeable for the job satisfaction of the employees, the efficiency of the company, as well as the bottom line.

As a Keynote speaker and Facilitator of team-days and workshops, Malene operates with a vision of spotting and developing talent potentials within the companies, since it creates a foundation for a much more attractive and sustainable business, which maintains, develops, and attracts even more talents. Malene is known for creating transformations during her speaking’s and workshops. She does this in combination with the Play Your Talent quiz, behavioural design, neuroscience, and habits. All of this is spiced with humour and inspiring case examples from the corporate business society and Malene's own private life.

The Organizing Committee PhD Day 2021

 Angela Herengt, Department of Biomedicine

 Ankur Razdan, Department of Dentistry and Oral Health

 Bente Pedersen, PhD and Talent Administration

 Charlotte Hansen Gabel, Department of Public Health

 Ellen Hollands Steffensen, Department of Clinical Medicine

 Ellen Lund Schaldemose, Department of Clinical Medicine

 Fabio Renato Manzolli Leite, Chair, Department of Dentistry and Oral Health

 Henning Grønbæk, Department of Clinical Medicine

 Jacob Thyrsted Jensen, Co-chair, Department of Biomedicine

 Julia Blay Cadanet, Department of Biomedicine

 Katia Soud, Department of Biomedicine

 Laura Øllegaard Johnsen, Department of Biomedicine

 Lene Krarup Monrad, PhD and Talent Administration

 Lina Bukowski, Department of Forensic Medicine

 Louise Hermann Poulsen, Department of Dentistry and Oral Health

 Luisa Schertel Cassiano, Department of Dentistry and Oral Health

 Mads Ronald Dahl, Centre for Educational Development

 Merete Bjerrum, Department of Public Health

 Pernille Louise Kjeldsen, Department of Clinical Medicine

 Rikke Nielsen, Department of Biomedicine

 Signe Mosegaard, Department of Clinical Medicine

Social media:

Facebook: PhD Association Health - #phdday2021

Session chairs

Find abstract titles and abstracts belonging to your session by searching session name.

Fogh Nielsen Competition

Søren Kragh Moestrup and Pernille Louise Kjeldsen (co-chair)

Oral sessions

Senior chairs - name Oral session

Poul Henning Jensen 1

Gregers Wegener 1

Francesco d'Amore 2

Michael Horsman 2

Bent Deleuran 3

Karin Birkenkamp-Demtröder 3

Henning Grønbæk 4

Christina Dahm 4

Anna Halling Folkmar Andersen 5

Inger Mechlenburg 5

Co-chairs - name Oral session Monica Dahlstrup Sietam 1

Erik Jørgensen 2

Frederik Boe Hansen 3

Sebastian Deisting Skejø 4

Katrine Brodersen 5

Poster sessions

Senior chairs - name Poster session

Pinar Bor 1

Mette Deleuran 2

Erling Pedersen 3

Anna Starnawska 4

Samuel Windross 5

Jasper Nijkamp 6

Christine Parsons 7

Mette Bjerre 8

Mette Tranberg Nielsen 9

Rubens Spin-Neto 10

Vladimir Matchkov 11

Co-chairs - name Poster session

Maria Louise Gamborg 1

Marlene Nielsen 1

Lars Bossen 2

Martin F. Gude 2

Maria Skydt Lindgren 3

Susanne Boel Graversen 3

Christine Ahrends 4

Marie Dahlstrøm 4

Amin Zakeri 5

Ensieh Farahani 5

Emil Thomsen 6

Torben Hoffmann 7

Louise Møller 7

Thorsten Rasmussen 8

Jeyanthini Risikesan 8

Laura Patricia Kaplan 9

Randi Istrup Juul 9

Helle K. Østergaard 10

Johan Hermansen 11

Michael Nørregaard Vinkel 11

Flash talk sessions

Senior chairs - name Flash talk session

Samia Joca 1

Peter Bross 2

Lau Møller Andersen 3

Vera Ehrenstein 4

Jesper Hjortdal 5

Simon Gabriel Comerma Steffensen 6

Ellen Mikkelsen 7

Lars Dyrskjøt Andersen 8

Jacob Johansen 9

Stinne Greisen 10

Johan Palmfeldt 11

Peter Jepsen 12

Astrid Juhl Terkelsen 13

Anne Hammer 14

Vassilis Sevdalis 15

Morten Schmidt 16

Co-chairs - name Flash talk session

Lixiang Jiang 1

Kristian Stær 1

Line Winther Gustafson 2 Christina Valbirk Konrad 2

Christine Ilkjær 3

Emma Bollmann Hansen 3

Janni Kjærgard Thillemann 4

Benjamin Mac Donald 4

Bodil B. Jørgensen 5

Kathrine Agergård Kaspersen 5

Zarmiga Karunanithi 6

Tara Ballav Adhikari 7

Mai Christiansen Arlien-Søborg 8 Solveig Kärk Abildtrup Larsen 8

Raul Argota-Perez 9

Olesya Svystun 10

Jesper Emil Jakobsgaard 10

Marc Opfermann 11

Simon Grund Sørensen 12

Louise Sofia Madsen 12

Timo Kvamme 13

Jeppe Schaldemose 13

Michelle Mølgaard Thomsen 14

Rasmus Espersen 14

Peter Bo Jørgensen 15

Michal Frumer 15

Karin Rosenkilde Laursen 16 Nina Breinholt Stærke 17

Lotte Sørensen 17

Session overview

Find abstract titles and abstracts by searching your name or session.

Fogh-Nielsen Competition

2. Kasper G. Lauridsen 3. Thor Haahr

Oral sessions

Oral session 1: Neurology and psychiatry

1. Anita Tønder Nielsen 2. Astrid Tuborgh

3. Bardia Varastehmoradi 4. Katrine Andersen 5. Merete Tonnesen 6. Mustafa Aykut Kural

Oral session 2: Oncology

1. Ann Taber

2. Aska Drljevic-Nielsen 3. Line Stensig Lynggaard 4. Marie Louise Milo

5. Sofie Stokkebro Schmøkel 6. Aamod Shrestha

Oral session 3: Preclinical models and patient studies

1. Charlotte Ernst

2. Hannah Brogård Andersen 3. Jonathan Yde

4. Martin Mæng Bjørklund 5. Signe Krejbjerg Jeppesen 6. Silja Hansen

Oral session 4: Public health and epidemiology

1. Astrid Boennelykke 2. Elena Dudukina

3. Jose Cerdan de las Heras 4. Line Elmerdahl Frederiksen 5. Louise Lilleøre Kjeldsen

Oral session 5: Immunology and skeleton

1. Emil Toft Petersen 2. Gitte Valentin 3. Jacob Thyrsted 4. Jeanette Trøstrup

5. Sabine Frølich Maarbjerg

Poster sessions

Poster session 1

1. André H. Dias

2. Anna Sofie Koefoed 3. Birgit Alsbjerg

4. Camilla Omann Christensen 5. Mette Lauge Kristensen 6. Morten Bjørn Jensen 7. Nanna Husted Jensen 8. Ninna Hinchely Ebdrup 9. Sara Bønløkke

10. Simon Jensen

11. Søren Reinhold Jakobsen

Poster session 2

1. Alexandra Golabek Christiansen 2. Bjørn Kristensen Fabian-Jessing 3. Charlotte Lock Rud

4. Claudia Jaensch

5. Frederikke Schønfeldt Troelsen 6. Kenneth Thomsen

7. Nils Skajaa

8. Simon Mark Dahl Baunwall 9. Tora Haug

Poster session 3

1. Anne Høy Seemann Vestergaard 2. Cathrine Bell

3. Christina Voss Ernstsen 4. Frederik Prip

5. Lisa Fønss Rasmussen

6. Lise Skovgaard Svingel 7. Maria Bisgaard Bengtsen 8. Peder Berg

9. Thomas Karmark Dreyer 10. Tina Kissow Lildal

11. Troels Kjærskov Hansen

Poster session 4

1. Alana Pinheiro

2. Ellen Lund Schaldemose 3. Hamed Zaer

4. Kasper Lolk 5. Katarzyna Grycel 6. Lasse Stensvig Madsen 7. Nadia Flensted Høgholt 8. Nikolaj Bøgh

9. Simone Larsen Bærentzen 10. Sine Mette Øgendahl Buus 11. Tobias Glaston Stærmose

Poster session 5

1. Alexey Ferapontov 2. Anne Sophie Schou 3. Gry Høst Dørflinger

4. Jacob Rudjord Therkildsen 5. Jacobina Kristiansen 6. Julia Blay Cadanet 7. Kamilla Vandsø Petersen 8. Marie K. Jessen

9. Mastaneh Afshar 10. Mateo Sokac

11. Stine Høvring Godsk

Poster session 6

1. Anders Dyhr Sandgaard 2. Buket Öztürk Esen 3. Clara Albiñana 4. Emil Nielsen Holck 5. Emil Michael Pedersen 6. Helene Honoré

7. Jintao Ren

8. Laura Barrett Ryø 9. Lia Valdetaro

11. Thorkild Terkelsen

Poster session 7

1. Anna Krogh Andreassen 2. Anne Timm

3. Anne Sophie Lind Helligsoe 4. Charlotte Dyrehave

5. Christina Bruun Knudsen 6. Christopher Rohde 7. Emely Ek Blæhr 8. Kristoffer Højgaard 9. Lene Klem Olesen 10. Louise Binow Kjær

11. Susanne Gundersborg Sandbøl

Poster session 8

1. Andreas Ebbehøj

2. Christine Bodelund Christiansen 3. Jie Zhang

4. Lauge Vammen

5. Marie Ernst Christensen 6. Mette Hansen Viuff

7. Mette Glavind Bülow Pedersen 8. Pia Johansson Heinsvig

9. Søren Gullaksen 10. Xiaoli Hu

11. Zheer Husain

Poster session 9

1. Anna Cecilie Lefèvre 2. Ditte Sigaard Christensen 3. Mads Sandahl

4. Mette Abildgaard Pedersen 5. Mette Tiedemann Skipper 6. Nicolai Juel Toft

7. Ninna Brix 8. Sarannya E 9. Simone Weiss 10. Stine Høgsholt

11. Søren Thorgaard Bønløkke

Poster session 10

1. Cecilie Rud Budtz

2. Christina Frølich Frandsen 3. Jakob Bie Granild-Jensen 4. Jakob Wang

5. Line Thams 6. Mikkel Bo Brent 7. Niels Moeslund 8. Philip Therkildsen 9. Rosa Marie Kiil 10. Siska Bjørn 11. Søren Mose

Poster session 11

1. Anne Dybro

2. Birgitte Krogsgaard Andersen 3. Jakob Nyvad

4. Johannes Enevoldsen

5. Kristian Hylleberg Christensen 6. Laust Dupont Rasmussen 7. Mia Klinkvort Kempel 8. Mikael Fink Vallentin 9. Nicklas Vinter

10. Sivagowry Rasalingam Mørk 11. Stine Rosenstrøm

Flash talk sessions

Flash talk session 1

1. Ahmed Sigad 2. Anders Shehab 3. Andreas Andersen

4. Camilla Termansen Erichsen 5. Daniel Mosgaard Soerensen 6. Mette Dahl Diechmann 7. Mishal Fayyaz

8. Sakeerthi Thambiappa 9. Teresa Haugaard Nielsen 10. Thomas Haugaard Thorsen

Flash talk session 2

1. Anne Vilsgaard Weibrecht 2. Emma Faddy

3. Ian Mees

4. Kjerstine Breintoft Kristensen

5. Malthe Alexander Knudsgaard Wiis 6. Maria Strandbo Schmidt Jensen 7. Nadia Thrane Hovgesen

8. Sofie Stampe

9. Sofie Møller Ølgaard 10. Tue Nguyen

Flash talk session 3

1. Anna Schultz-Lebahn 2. Isabella Hangaard Rüdiger

3. Maiken Faklam Dalsgaard Knudsen 4. Maj Wiendel Jakobsen

5. Maria Høybye

6. Marlice Zwanenburg 7. Mette Marie Baunsgaard 8. Naja Stausholm Winther 9. Sebastian Nielsen 10. Thomas Jensen

Flash talk session 4

1. Amanda Lynggaard Riis 2. Christian Emil Brinck 3. Esben Madsen 4. Frederik Teicher Kirk 5. Jakob Rønnow Sand 6. Martin Locht Pedersen

7. Nynne Emilie Fagerlund Hummelshøj 8. Sofie Hasseris Jensen

9. Trine Lillelund

Flash talk session 5

1. Amalie Munk Eefsen 2. Anna R. Wieghorst 3. Anne Hjorth Thomsen 4. Daniel Lindbo

5. Fie Langmann 6. Katrine Johannsen

7. Morten Brok Molbech Madsen 8. Sara Marcus

9. Signe Freja Storgaard

Flash talk session 6

1. Daniel Fyenbo 2. Kasper Bonnesen 3. Kristoffer Berg-Hansen

4. Maria Hee Jung Park Frausing 5. Nigopan Gopalasingam 6. Nikola Stankovic

7. Oliver Buchhave Pedersen 8. Pernille Gro Thrane

9. Tanja Charlotte Frederiksen 10. Thien Luong

Flash talk session 7

1. Anders Isaksen

2. Anne Gaml-Sørensen 3. Dorthe Dalstrup Jakobsen 4. Eeva-Liisa Røssell Johansen 5. Ellen Hollands Steffensen

6. Nicholas Papadomanolakis-Pakis 7. Sia Kromann Nicolaisen

8. Tanja Sofie Hansen 9. Trine Worm Thøgersen

Flash talk session 8

1. Anne Bruun Rovsing 2. Eleni Kanouta 3. Irina Manhoobi 4. Judit Kisistók 5. Julie Mondahl 6. Karen Wind

7. Kristian Wiborg Antonsen 8. Lasse Refsgaard

9. Lau Amdisen 10. Nikola Mikic

Flash talk session 9

1. Andreas Hagner 2. Louise Bach Callesen 3. Maiken Parm Ulhøi 4. Martin Rasmussen 5. Merete Eybye Dam 6. Mikkel Lundbech

8. Sia Viborg Lindskrog 9. Simone Stensgaard 10. Sixten Harborg

Flash talk session 10

1. Cristina Rocha Exposto 2. Frederik Duch

3. Joao Fuglsig

4. Lisa Cecilie Urup Reimer 5. Luisa Schertel Cassiano 6. Maithri Aspari

7. Marie Anneberg Brahe 8. Shuting Yang

9. Stian Langgård Jørgensen 10. Troels Kjeldsen

Flash talk session 11

1. Amanda Bæk

2. Anne Kathrine Nissen Pedersen 3. Mette Louise Blouner Gram Kjærulff 4. Nanna Steengaard Mikkelsen 5. Pernille Rikvold

6. Sara Brun

7. Sarah Bisgaard Olesen

8.

9.

Flash talk session 12

1. Anne Catrine Daugaard Mikkelsen 2. Anne Karmisholt Grosen

3. Ditte Smed Kornum 4. Gencer Kurt

5. Ian Møller-Nielsen 6. Katrine Lundby Høyer 7. Lotte Lindgreen Eriksen 8. Rasmus Hvidbjerg Gantzel 9. Rogini Balachandran 10. Sham Al-Mashadi Dahl

Flash talk session 13

1. Erik Kaadt

2. Kathrine Synne Weile

3. Laura Linnea Määttä 4. Lina Bukowski

5. Lucie Woloszczukova 6. Mads Qvist Ebbesen 7. Mikkel Karl Emil Nygaard 8. Thomas Beck Lindhardt 9. Vinni Faber Rasmussen

Flash talk session 14

1. Anna Lund Rasmussen 2. Johanna Laura Heinz 3. Kathrine Dyhr Lycke

4. Lene Ugilt Pagter Ludvigsen 5. Line Dahl Jeppesen

6. Mikkel Illemann Johansen 7. Naziia Kurmasheva 8. Rikke Kamp Damgaard 9. Sofine Heilskov

10. Thomas Emmanuel 11. Toke Alstrup

Flash talk session 15

1. Aline Dragosits 2. Britt Borg

3. Cecilie Schultz Isaksen 4. Emmanuel Musoni-Rwililiza 5. Eva Bølling-Ladegaard 6. Julie Grinderslev Donskov 7. Julie Duval Jensen

8. Kevin Marks 9. Lotte Veddum 10. Shokouh Arjmand

Flash talk session 16

1. Andreas Bugge Tinggaard 2. Anita Dittrich

3. Benjamin Kelly

4. Bertil Thyrsted Ladefoged 5. Cecilia Hvitfeldt Fuglsang 6. Christine Gyldenkerne 7. Julie Hauer Vendelbo 8. Maiken Bay Ravn

9. Mette Østergaard Thunbo

10. Tabia Volqvartz

Flash talk session 17

1. Anders Breinbjerg

2. Camilla Grønkjær Jensen 3. Frederik Husum Mårup 4. Jean-Claude Kresse 5. Louise Engelbrecht Buur 6. Marie Bodilsen Nielsen 7. Michael Schou Jensen 8. Simon Kok Jensen 9. Simone Brandt 10. Stefanie Körner

PHD DAY 2021

Abstracts

Fogh Nielsen Competition

STUDYING REFUGEE HEALTH USING PROPENSITY SCORE WEIGHTING AND MULTIPLE IMPUTATION

Andreas Halgreen Eiset, Dept. Public Health, Aarhus University

Morten Frydenberg, Dept. Public Health, Aarhus University ;Michaelangelo P. Aoun, Faculty of Medical Sciences, the Lebanese University; Ramzi S. Haddad, Faculty of Medical Sciences, the Lebanese University; Wadih J Naja, Faculty of Medical Sciences, the Lebanese University

Introduction

Refugees suffer from high risk of anxiety, depression and post-traumatic stress disorder (PTSD) and are exposed to many risk-factors before, during and after migrating. No studies have examined if refugees undergoing long-distance migration are at increased risk of mental health disorders when compared with those who stay in the region of origin. Here, we estimate the association between long-distance migration and PTSD in Syrian refugees in Lebanon and Denmark.

Methods

In this cross-sectional study with one-stage cluster-randomised sampling newly arrived adult Syrian refugees were included between 2016 and 2019 in refugee camps and asylum seeker centres and assessed for PTSD using the HTQ-scale. The statistical

methodology to give an unbiased estimate of association, including combining multiply imputation and propensity score weighting, was developed and implemented in a computer programme.

Results

We invited 751 individuals and included 712 (95%). The unadjusted prevalence of PTSD was higher in Denmark (60.18%) compared with Lebanon (55.12%). However, the study populations differed on key variables such as sex (female: 73% in Lebanon, 47% in Denmark) and experience of violence (24% in Lebanon, 39% in Denmark). Our method was able to balance out these differences. At time of submission the main analysis to produce unbiased estimates of the association between long-distance migration and PTSD is processing.

Discussion

This study will discuss the association between long-distance migration and PTSD in refugees; it sheds light on a debilitating mental health disorder in recently arrived refugees to focus the attention of researchers and mental health practitioners.

1

IMPROVING OUTCOMES FROM IN-HOSPITAL CARDIAC ARREST: STUDIES ON CARDIAC ARREST TEAMS

Kasper Glerup Lauridsen, Department of Medicine, Randers Regional Hospital Ichiro Watanabe, Children's Hospital of Philadelphia

Bo Løfgren, Randers Regional Hospital Adam Cheng, Alberta Children's Hospital

Jordan Duval-Arnould, Johns Hopkins University Hospital Elizabeth A. Hunt, Johns Hopkins University Hospital Grace L. Good, Children's Hospital of Philadelphia Dana Niles, Children's Hospital of Philadelphia Robert A. Berg, Children's Hospital of Philadelphia Akira Nishisaki, Children's Hospital of Philadelphia Vinay M Nadkarni, Children's Hospital of Philadelphia

Aim: We aimed to achieve consensus and evaluate feasibility and efficacy using standardised communication during cardiopulmonary resuscitation (CPR) events.

Methods: Modified Delphi consensus process to design standardised communication.

Feasibility was tested in 16 simulated CPR scenarios randomized (1:1) to standardised [INTERVENTION] vs. closed-loop communication [CONTROL]. Adherence and efficacy (duration of CC pauses for defibrillation, intubation, rhythm check) was assessed by video recording. Mental demand and frustration were assessed by NASA task load index subscales.

Results: Consensus for standardised communication included: 1) team preparation 15- 30 seconds before CC interruption, 2) pre-interruption countdown synchronized with last 5 CCs, 3) specific action words for defibrillation, intubation, and interrupting/resuming CCs. Median (Q1,Q3) adherence to standardised phrases was 98% (80%,100%). Efficacy analysis showed a median [Q1,Q3] peri-shock pause of 5.1 sec. [4.4; 5.8] vs. 7.5 sec. [6.3;

8.8] seconds, p<0.001, intubation pause of 3.8 sec. [3.6; 5.0] vs. 6.9 sec. [4.8; 10.1]

seconds, p=0.03, rhythm check pause of 4.2 [3.2,5.7] vs. 8.6 [5.0,10.5] seconds, p<0.001, median frustration index of 10/100 [5,20] vs. 35/100 [25,50], p<0.001, and median mental demand load of 55/100 [30,70] vs. 65/100 [50,85], p=0.41 for standardised vs.

closed loop communication.

Conclusion: We demonstrated feasibility of using consensus-based standardised

communication that was associated with shorter CC pauses for defibrillation, intubation, and rhythm checks without increasing frustration index or mental demand compared to current best practice, closed-loop communication.

DIAGNOSIS AND TREATMENT OF ABNORMAL VAGINAL MICROBIOTA TO IMPROVE REPRODUCTIVE OUTCOME IN IVF PATIENTS

Thor Haahr, The Fertility Clinic, Skive Regional Hospital, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Humaidan P, The Fertility Clinic Skive, Skive Regional Hospital, Department of Clinical Medicine, Aarhus University, Denmark

J.S. Jensen, Department of Bacteria, Parasites and Fungi, Statens Serum Institute, Copenhagen, Denmark

A.C. Ingham, Department of Bacteria, Parasites and Fungi, Statens Serum Institute, Copenhagen, Denmark

N Uldbjerg, Department of Clinical Medicine, Aarhus University, Denmark

This PhD project investigates the genital tract microbiota and its potential impact on reproductive outcomes of in vitro fertilization (IVF) treatment. The initial focus of the PhD project has been to establish a reliable diagnostic tool to identify IVF women at risk of poor reproductive outcome due to a hypothesized infectious aetiology. The idea is to use the vaginal microbiota as a proxy to identify a dysbiotic endometrial microbiota – due to ascending infection - which would hamper embryo implantation and; thus, successful pregnancy. The novel diagnosis termed abnormal vaginal microbiota (AVM) is

associated to poor reproductive outcome in IVF patients, that is clinical pregnancy rates of 9% in patients with AVM versus 44% in patients with normal vaginal microbiota. A systematic review and meta-analysis underlines the importance of correct diagnosis of vaginal dysbiosis and optimal selection of patients. Next, the ascending infection hypothesis is investigated by comparing endometrial microbiota to the vaginal and cervical microbiota in IVF patients and as compared to healthy oocyte donors. This clearly shows evidence of ascending infection from the vagina to the endometrium although the bacterial biomass is much lower in the endometrium. Finally, the treatment of abnormal vaginal microbiota using a combination of clindamycin and a live

biotherapeutic drug containing Lactobacillus crispatus is explored in a subset of patients undergoing an RCT. In conclusion, the jury is still out considering whether abnormal vaginal microbiota and its treatment should be considered for future IVF treatment, but this pioneering research has the potential to change clinical practice.

3

Oral session 1: Neurology and pcychiatry

SCHIZOPHRENIA AND COMORBID DIABETES: DOES THE ADDED SCRUTINY ASSOCIATED WITH CLOZAPINE USE PREVENT ADVERSE HEALTH

OUTCOMES?

Anita Tønder, National Centre for Register-based Research, Aarhus BSS, Aarhus University, Denmark, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Denmark, Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Denmark

Janne Tidselbak Larsen, National Centre for Register-based Research, Aarhus BSS, Aarhus University, Denmark, The Lundbeck Foundation Initiative for Integrative

Psychiatric Research (iPSYCH), Denmark, Trine Munk-Olsen, National Centre for Register- based Research, Aarhus BSS, Aarhus University, Denmark, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Denmark, Dan Siskind, University of Queensland School of Medicine, Brisbane, Queensland, Australia, Metro South

Addiction and Mental Health Service, Brisbane, Queensland, Australia, Queensland Centre for Mental Health Research, Brisbane, Queensland, Australia, John J. McGrath, National Centre for Register-based Research, Aarhus BSS, Aarhus University, Denmark, Queensland Centre for Mental Health Research, Brisbane, Queensland, Australia, Queensland Brain Institute, University of Queensland, St Lucia, Queensland, Australia, Thomas Munk Laursen, National Centre for Register-based Research, Aarhus BSS, Aarhus University, Denmark,The Lundbeck Foundation Initiative for Integrative Psychiatric

Research (iPSYCH), Denmark Objective

Excess mortality in individuals with schizophrenia may be partly due to lack of

monitoring of comorbid general medical conditions and their associated complications.

We hypothesized that increased contact with health services may improve early intervention and reduce the risk of diabetic complications and mortality. We tested this by comparing rates of diabetes complications and mortality among individuals with schizophrenia and diabetes using clozapine, a medication that requires more frequent clinical contact, and no use of clozaopine.

Methods

We conducted a cohort study using nationwide population-based registers. Incidence rate ratios (IRR) of diabetic complications and mortality rate ratios (MRR) were estimated by Cox regression.

Results

For individuals with schizophrenia and diabetes using clozapine, compared to those with schizophrenia and diabetes not using clozapine, the incidence of diabetic complications

1.42). For both sexes, the mortality rates were similar for those with schizophrenia and diabetes who were prescribed clozapine (females MRR= 1.04, 95% CI, (0.82-1.32); males MRR= 0.96, 95% CI, (0.79-1.17)) compared to those who were not.

Conclusion

A history of clozapine use was associated with lower rates of diabetic complications in men, despite the increased risks of glucose dysregulation associated with clozapine.

Overall mortality was not different between those using clozapine and not using clozapine. Our results could guide future studies about individuals with schizophrenia using clozapine.

ARE THERE CHANGES IN ATTACHMENT DIMENSIONS IN YOUNG ADULTS AFTER THE EXPERIENCE OF A CONCUSSION:

FINDINGS FROM A LONGITUDINAL CLINICAL COHORT STUDY

Astrid Tuborgh, Department of Child and Adolescent Psychiatry, Research Unit, Psychiatry, Aarhus University Hospital, Denmark. E-mail: asttub@rm.dk

Svendsen SW (3,4,5), Elklit A (6), Hunter J(7), Jensen JS(8), Schröder A(8), Nielsen JF(3), Thastum MM(3,8), Næss-Schmidt ET(3), Rask CU( 1,2).

1 Department of Child and Adolescent Psychiatry, Research Unit, Psychiatry, Aarhus University Hospital, Denmark.

2 Department of Clinical Medicine, Aarhus University, Denmark.

3 Hammel Neurorehabilitation Centre and University Research Clinic, Aarhus University, Denmark.

4 Department of Occupational and Environmental Medicine, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark.

5 Department of Public Health, Section of Environmental Health, University of Copenhagen, Denmark.

6 Department of Psychology, National Center of Psycho-traumatology, University of Southern Denmark, Denmark.

7 Department of Psychiatry, Mount Sinai Hospital, University of Toronto, Canada.

8 Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Denmark.*

Background

Adult attachment dimensions (anxiety and avoidance) are thought to be fairly stable across time, but may change in response to a variety of life-events. This study

investigated the potential changes of attachment dimensions in young people with a concussion within the first 9 months post-injury.

5

Methods

This longitudinal study was embedded in an epidemiological study of young people, aged 15-30 years, all diagnosed with concussion (n=988). Data was obtained from an administrative database and patients filled out questionnaires 3 (T1) and 9 (T2) months post-injury. Mean-level changes in attachment dimensions (range 1-7) were examined by a mixed model regression analysis with separate models including the following covariates: sex, age, post-concussion symptoms, post-traumatic stress symptoms and social support and a final model including all covariates.

Results

Out of 958 eligible patients at T1, 416 also responded at T2 (43.4%). The mean changes of both attachment dimensions were clinically insignificant (attachment anxiety: β = -0.07 (95% CI: -0.22; 0.08), attachment avoidance: β = 0.00 (95% CI: -0.11; 0.11). Adjusting for covariates did not affect the results.

Conclusion

The results suggest that the experience of a health-related life-event like a concussion does not lead to changes in young peoples’ attachment dimensions from 3 to 9 months' post-injury. As particular attachment dimensions may be associated with different trajectories of illness response to a concussion, self-report on attachment dimensions early post-injury may prove valuable for more tailored interventions for this patient group.

OPIOID SYSTEM HAS AN IMPACT ON HPA AXIS, COGNITIVE PROCESSES, AND DEPRESSION

Bardia Varastehmoradi, Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark

Karen L. Smith 2, Connie Sánchez 1,2 , Emma Robinson 3, Gregers Wegener 1

1 Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark

2 Department of Biology, Alkermes Inc., Waltham, MA, USA

3 School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK Negative cognitive affective bias (CAB) may appear as one of the symptoms in

depressed patients. Endogenous opioid peptides can have effect on mood. Therefore in this project, we studied the role of opioid system CAB and depression.

The affective bias test was used to measure the CAB on female Sprague Dawley (SD) rats. During pairing days, the animals chose a bowl contained reward or not. The reward

the animal chose one of the substrates during 30 trials. Based on the number of choices, the CAB was calculated. The CAB of corticosterone (CORT) and the kappa opioid receptor (KOR) agonist, U50488, was measured in ABT. The effect of DIPPA (KOR antagonist) on CAB of CORT-treated animals was also assessed by ABT. Level of dynorphin (DYN) and CORT in blood were measured by EIA and ELISA 30 minutes following CORT and U50488 treatment. The brains were collected and kept in -80 for further study.

We found U50488 (5mg/kg) and CORT (10mg/kg) significantly induced negative biases, while DIPPA (5mg/kg) eliminated CORT-induced negative biases. The CORT concentration in serum was significantly higher in U50488-treated group than control (p<0.01). The western blot analysis shows that p38 mitogen-activated protein

kinase(MAPK) was phosphorylated more in the frontal cortex following a single dose of U50488 compared to controls, while c-fos was decreased in U50488 treated animals.

The data supports that the opioid system can be proposed as putative therapeutic targets in depression due to modulating cognitive functions and mood levels.

Keywords: opioid, cognitive affective bias, depression

MEASURING SYNAPTIC LOSS IN VIVO IN PATIENTS WITH PARKINSON’S DISEASE (PD) AND EARLY DEMENTIA WITH LEWY BODIES (DLB) – A PET STUDY

Katrine Andersen - Department of Nuclear Medicine and PET Centre, Aarhus University Hospital

A.K Hansen, P. Borghammer

Department of Nuclear Medicine and PET Centre, Aarhus University Hospital Introduction

Patients with PD often develop cognitive decline and dementia during the course of disease; however, the underlying causes are poorly understood. The pathological processes in PD are hypothesized to begin decades before clinical diagnosis and include a variety of synaptic alterations. Previously, these changes were thought to be limited to the dopaminergic system. Recent evidence, however, suggests that more generalized synaptic degeneration occurs. Thus, an improved understanding of the overall synaptic loss in PD and its relation to cognitive decline is needed.

Method

7

Using in vivo high-resolution PET imaging and novel synaptic vesicle glycoprotein 2A (SV2A) radioligand [11C]UCB-J, this study assessed the density of synapses in non- demented PD subjects (N=21), demented PD subjects, subjects with DLB (N=12) and matched healthy controls (HC) (N=15).

Results

Our preliminary analyses revealed that when compared with HC, the PD group exhibited lower SV2A density in substantia nigra(SN) (SUVR -27%). SN contains the majority of dopaminergic neurons and these are known to degenerate in PD. In addition, PDD/DLB subjects show significantly lower SV2A specific binding in cortical regions; frontal lobe orbital gyrus (SUVR -25%) partial lobe gyrus (SUVR -25%) occipital lobe cuneus (SUVR - 26%) and SN (SUVR -46%).

Conclusion

Our preliminary results indicate that synaptic integrity measured by [11C]UCB-J is reduced in subcortical regions central to the pathogenesis of PD, but also in cortical regions in demented patients. Overall, SV2A holds promise for in vivo imaging of synaptic loss and possibly diagnosis and assessment of disease progression in PD and DLB patients.

POSTPONING THE FUTURE, MAXIMIZING THE PRESENT.

HOPES AND GOALS IN PARKINSON'S DISEASE REHABILITATION

Merete Tonnesen, Department of Public Health, Aarhus University Claus Vinther Nielsen, Department of Public Health, Aarhus University

Parkinson's disease is a progressive and neuro-degenerative disease, currently with no cure. With the disease comes an uncertainty of life: how bad will it be, and when? Living with Parkinson's disease, rehabilitees navigate this space of future uncertainty. We aimed to explore how they navigate and orientate towards the future, by putting a lens to their goals and hopes.

The study builds on a multisited fieldwork in Denmark. The first author was 'hospitalized' with 20 persons with Parkinson's disease during their rehabilitation stay and followed them, their goals and hopes over two years through different landscapes – their homes, neurologists, and physiotherapists following the flow (of goals and hopes) between the sites, and paths taken between them. Participant observation, interviews, and document analysis were used.

Informants preferred future near, short term and concrete goals. Most goals concerned mobility, long term goals concerned their social identity: be able to work/play with grandchildren. We found a generalized hope (you have to have hope to live), and particularized hope: a generational or extended hope of a cure or better treatment if not for themselves then the next generation with Parkinson's disease, a personal/social hope to retain identity and the activities associated with the identity, and a not-hope or

avoidance hope 'I hope I will not' - end in a wheelchair, lose ability to talk. Informants located hope in 1. medical research, 2. others, 3. training. Agency was important - to live in the now, train, and partake in medical research. We conclude that rehabilitees

engage in time-work, trying to postpone the future by maximizing the present.

THE INFLUENCE OF THE NUMBER OF EPILEPTIFORM DISCHARGES AND

THEIR MORPHOLOGY ON THE DIAGNOSTIC ACCURACY: HOW MANY TIMES DO YOU NEED TO SPOT A SPIKE IN A RECORDING?

Mustafa Aykut Kural; Department of Clinical Neurophysiology, Aarhus

Background: The International Federation of Clinical Neurophysiology (IFCN) suggested six criteria in EEG, so that presence of at least 4 of them defines a waveform as

Epileptiform Discharges (ED). However, both the operational definition of the IFCN criteria and the clinical validation studies are based on the single discharge. The aim of this study was to assess the diagnostic value of pattern repetition as the similarity of the waveform and frequency of occurrence.

Methods: EEGs samples of 20-minutes duration each, from 60 consecutive patients with epilepsy and non-epileptic paroxysmal events were reviewed separately by three raters.

EDs were defined in EEG recordings using the following strategies: different thresholds (3 to 6 fulfilled criteria), optimized IFCN criteria (criteria number 1-4-6), and without taking into account IFCN criteria based on different numbers of ED (1 to 5). Overall accuracy was determined for each rater and the majority decisions for each sample

Results: Using a threshold of 5 criteria based on single discharge having a specificity of 96% was achieved at a sensitivity of 70% and an accuracy of 85%. Results in optimized criteria with two pattern repetitions, cut off value of 4 criteria with four repetitions, and cut off value of 3 criteria with five repetitions have achieved a specificity of over 95 percent.

Using a combination of these strategies and thresholds resulted in a specificity of 96.76%

and sensitivity of 80%,

Conclusion: The combined strategy of visual feature extraction and number of pattern repetitions resulted in a high sensitivity and specificity and are suitable for

implementation into clinical practice.

9

Oral session 2: Oncology

MOLECULAR CORRELATES OF CISPLATIN-BASED CHEMOTHERAPY

RESPONSE IN MUSCLE INVASIVE BLADDER CANCER BY INTEGRATED MULTI- OMICS ANALYSIS

Ann Taber, Department of Molecular Medicine, AUH

E. Christensen,Department of Molecular Medicine, AUH; P. Lamy, Department of

Molecular Medicine, AUH; I. Nordentoft, Department of Molecular Medicine, AUH; F. Prip, Department of Molecular Medicine, AUH; S.V. Lindskrog, Department of Molecular Medicine, AUH; K. Birkenkamp-Demtröde, Department of Molecular Medicine, AUH;

M. Knudsen, Department of Molecular Medicine; T. Steiniche, Department of Pathology, AUH; M. Agerbæk, Department of Oncology, AUH; J.B. Jensen, Department of Urology, AUH; L. Dyrskjøt, Department of Molecular Medicine, AUH

Background: Overtreatment with cisplatin-based chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC).

Methods: Here we performed a comprehensive multi-omics analysis (genomics, transcriptomics, epigenomics and proteomics) of 300 MIBC patients treated with chemotherapy to identify molecular correlates associated with response.

Results: DNA-based associations with response converged on genomic instability driven by a high number of chromosomal alterations, indels, mutations in a tri-nucleotide signature 5 context and/or BRCA2 mutations. We assigned patients to high (HGI) and low genomic instability (LGI) groups, and found that patients with HGI had a response rate of 71% vs. 49% for patients with LGI (p=0.007). Expression data identified the

basal/squamous (Ba/Sq) gene expression subtype to be associated with poor response.

Low immune cell infiltration and low PD-1 protein expression were also associated with poor response. Through integration of genomic and transcriptomic data, we identified a group of patients with a high response rate (80%) characterized by HGI and non-Ba/Sq subtype and a group of patients with a low response rate (25%) characterized by LGI and Ba/Sq subtype (p<0.001).

Conclusion: Overall, our results highlight several molecular correlates of chemotherapy response and importantly, the integration of genomic instability and gene expression subtypes identified patient groups with vastly different response rates. If successfully validated, these findings could pave the way for future patient selecting and potentially minimize the current overtreatment of patients. Prospective validation is currently

ongoing: NCT04138628.

REASSURING RECIST V1.1 DEFINED PROGRESSION BY DYNAMIC

CONTRAST-ENHANCED COMPUTED TOMOGRAPHY IN METASTATIC RENAL CELL CARCINOMA

Aska Drljevic-Nielsen, Department of Oncology, Department of Radiology, Aarhus University Hospital, Denmark

F. Rasmussen, Department of Radiology; J.R. Mains; Department of Radiology, K. Thorup;

Department of Radiology, F. Donskov; Department of Oncology, Aarhus University Hospital, Denmark

Objectives: RECIST1.1 in metastatic cancer has limitations. Recently, DCE-CT identified Blood Volume (BV) and Blood Flow (BF) have shown promising results in response evaluation in mRCC. We assessed DCE-CT as an enhancement to RECIST1.1 in evaluating progressive disease (PD) in mRCC.

Methods: Deconvolution (deconv) and patlak (patlak) methods were used to quantify BV and BF in patients with mRCC treated with 1st line therapies baseline, 1 month after baseline and every 3rd month until PD. Compared with baseline, relative changes in BV(ΔBV) and BF(ΔBF) were assessed at each scan timepoint as categorical (≥20%) and continuous variables (20%-point). Adjusted for IMDC features and treatments, Cox proportional hazard models were used to assess the association between ΔBV/ΔBF and PD using two endpoints: firstly, time to progressive disease (PDtimepoint) and secondly, time to the scan timepoint prior to PDtimepoint (PDminus1timepoint).

Results: A total of 105 patients were included in the analysis. At PDminus1timepoint and PDtimepoint ΔBV/ΔBF could be analyzed for 64 and 62 patients, respectively.

ΔBVpatlak≥20% was associated with increased risk of PD at PDtimepoint (HR=2.43, 95%CI:1.49-3.96, P<0.001). Increased ΔBVpatlak and ΔBVdeconv were associated with increased risk of PD at PDtimepoint (HR= 1.05, 95% CI:1.03-1.08, P<0.001 & HR=1.11; 95%

CI: 1.07-1.15, P <0.001, respectively). At PDminus1timepoint, ΔBVdeconv and ΔBFdeconv≥20% were associated with an increased risk of PD (HR=1.14, 95%CI:1.01;1.28, P<0.030 & HR=1.81, 95% CI:1.08;3.04, P<0.022, respectively).

Conclusions: BV and BF may serve as a helping tool in identifying unequivocal PD as an enhancement to RECIST1

11

ASPARAGINASE ENCAPSULATED IN ERYTHROCYTES – A PROMISING ALTERNATIVE TO PEG-ASPARAGINASE IN CASE OF HYPERSENSITIVITY IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

Line Stensig Lynggaard, Child and Adolescent Healt, Aarhus University Hospital SG Hoejfeldt, Child and Adolescent Health, Aarhus University Hospital, Denmark L Moeller, Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark

G Vaitkeviciene, Center of Pediatric Oncology and Hematology, Children's hospital, affiliation of Vilnius University Hospital, Lithuania

C Langenskiöld, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden

AK Lehmann, Haukeland University Hospital, Department of hematology, Bergen, Norway

PM Lähteenmäki, Department of Pediatric and Adolescent Medicine, Turku University Hospital, Finland

K Lepik, Department of Hematology and Oncology, Tallinn Children's Hospital, Tallinn, Estonia

K Schmiegelow, Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark

BK Albertsen, Child and Adolescent Healt, Aarhus University Hospital , Denmark PEG-asparaginase (Peg-asp) is an important part of the treatment of acute

lymphoblastic leukemia (ALL) in children. Allergy is a common toxicity to PEG-asp. It is associated with inactivation of the drug and decreased survival, because of

discontinued therapy. Asparaginase encapsulated in erythrocytes (eryaspase) is an alternative formulation. The erythrocyte membrane protects asparaginase against elimination and prevents activation of the immune system, thus re-exposure to

asparaginase is possible. The aim of the study is to evaluate the safety and efficacy of eryaspase.

NOR-GRASPALL 2016 is a Nordic/Baltic multinational multicentre single-arm study for non-high risk patients with ALL and allergy to PEG-asp. Eryaspase replaces the

remaining doses of PEG-asp (1-7 doses, 150 IU/kg). Measurements of asparaginase enzyme activity (AEA) are used for treatment monitoring.

Since 2017 55 patients were included in the study, currently 37 patients completed follow-up. In total 171 doses were administered. 94.7% of the patients had adequate AEA (> 100IU/L) 14 days after eryaspase administration (Median AEA: 710 IU/L, [IQR:

406-1018]), 80.3% of the patients after 21 days (Median AEA: 505.5 IU/L [IQR: 173.5-

patient had a severe allergic reaction to eryaspase, four patients developed mild

symptoms of allergy, deemed related to eryaspase. No other severe adverse events with relation to eryaspase have been

Eryaspase consistently demonstrated prolonged AEA in patients with allergy to PEG-asp.

Treatment with eryaspase is well tolerated and is a promising alternative to PEG-asp in case of allergy.

RADIATION DOSE TO THE HEART AND CARDIAC SUBSTRUCTURES IN BREAST CANCER PATIENTS TREATED WITH CT-BASED RADIOTHERAPY

Marie Louise Holm Milo, Department of Experimental Clinical Oncology

J. Alsner, Department of Experimental Clinical Oncology, Aarhus University Hospital; TB Nyeng, Department of Medical Physics, Aarhus University Hospital; L Hoffmannn,

Department of Medical Physics, Aarhus University Hospital; LBJ Thorsen, Department of Oncology, Aarhus University Hospital; IL Jensen, Department of medical Physics, Aalborg University Hospital, HD Nissen, Department of medical Physics, Vejle Hospital, EL

Lorenzen, Department of Oncology, Odense University Hospital; L Refsgaard, Danish Center of Particle Therapy; SP Johnsen, department of Clinical Medicin, Aalborg

University Hospital; KM Nielsen, Department of Cardilology, Aarhus University Hospital, DS Møller, Department of Medical Physics, Aarhus University Hospital; BV Offersen,

department of Experimental Clinical Oncology, Aarhus University Hospital Background:

The aim of this study was to determine radiotherapy (RT) dose in relevant cardiac

substructures for breast cancer (BC) patients treated with CT-based RT and to estimate a dose-response relationship linking RT dose to RT-associated cardiac events.

Material and methods: We conducted a nested case-control study of cardiac events in a population-based cohort of 29,662 BC patients irradiated between 1999 and 2016 and treated with CT-based RT. The cohort included 273 cases diagnosed with cardiac event after BC irradiation and 546 controls. The controls were matched on age at BC diagnosis and year of diagnosis.

Each patient´s RT planning CT scan was collected and transferred to a software system.

In this system an automatically contouring atlas of the heart and cardiac substructures was generated. The Atlas was used for auto-segmentation on each CT scan from cases and controls. Dose-volume histograms were used to extract the mean RT doses for each structure.

13

Results: The average mean radiation doses to substructures will be reported (work in progress). Conditional logistic regression analysis will be used to obtain the odds ratio of cardiac events associated with radiation dose, comparing cases with matched controls.

The dose-response relationship will be estimated by modeling the cardiac event rate as Km(1+βd) where Km is a constant to each matched set of case and controls, β is the excess relative risk of cardiac event per unit increase in dose and d is the RT dose in Gy to the relevant cardiac substructure.

Conclusion: A dose-response relationship linking RT doses to substructures and cardiac events following adjuvant RT is essential as advanced RT technique.

DISSECTION OF THE TUMOR ECOSYSTEM IN BLADDER CANCER USING SINGLE NUCLEI SEQUENCING

Sofie Stokkebro Schmøkel, Department of Molecular Medicine (MOMA), AUH Iver Nordentoft*, Sia. V. Lindskrog*, Ann Taber*, Michael Knudsen*, Philippe Lamy*, Jørgen Bjerggard Jensen**, and Lars Dyrskjøt*,

* Department of Molecular Medicine (MOMA), AUH

** Department of Urology, AUH

A tumor is an ecosystem consisting of carcinoma cells, infiltrated immune cells, and cancer-associated fibroblasts. The ecosystem may support survival and progression of the cancer and may have a huge impact on treatment response. The advances of single cell genomics now make it possible to investigate the tumor ecosystem at single cell resolution, which may heighten our understanding of disease mechanisms, tumor heterogeneity and treatment response.

We have performed single nuclei RNA-Sequencing on frozen bladder tumors from 48 patients (10 Ta; 13 T1; 25 T2-4 tumors) with known clinical information and long term follow-up. Single nuclei libraries were made on the microfluidic platform, Drop-seq, followed by sequencing on a NovaSeq6000. For comparison, three biopsies have been analyzed using 10x Chromium, four biopsies have been analyzed using 10X Visium Spatial, and additional bulk exome- and total RNA-Sequencing have been carried out on sections from the same tumors.

A total of 106,863 nuclei (median: 1568 nuclei per patient) have now been analyzed.

unique expressed genes was detected per nuclei. Single nuclei sequencing data were visualized using UMAPs, and showed that nuclei isolated from high grade tumors clustered together across patients, the same applies for nuclei isolated from low grade tumors. Various cell populations were identified including epithelial cells, different populations of immune cells, and neuronal cells. We are currently performing comparative analysis of single nuclei and associated bulk whole exome- and RNA- Sequencing.

UTILIZATION OF CERVICAL CANCER SCREENING AMONG WOMEN IN NEPAL

Aamod Dhoj Shrestha, Third year PhD student, GP:Public Health

Center for Global Health, Department of Public Health, Aarhus University

D. Neupane, Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, United States;

S. Ghimire, Nepal Cancer Care Foundation, Lalitpur, Nepal;

C. Campbell, Usher Institute, University of Edinburgh, United Kingdom;

P. Kallestrup, Center for Global Health, Department of Public Health, Aarhus University, Denmark

Background: Cervical cancer continues to be a global public health concern and a leading cause of cancer deaths among Nepalese women. In spite of the availability of screening and treatment services in Nepal, the utilization of screening has been low. The objective of the study is to investigate the utilization of cervical cancer screening among women in a semi-urban area of Pokhara Metropolitan City of Nepal.

Methods: A community-based cross-sectional survey was carried out among 729

women aged 30-60 years, between April and June 2019. Participants were selected by systematic random sampling, and a door-to-door home visit was conducted for data collection. A pre-tested interviewer-administered Nepali questionnaire was used to collect information on socio-demographic variables and utilization on cervical cancer screening.

Results: The mean age (SD) of the participants was 45.9 ±7.7 years; the majority were married (86.7%). Among the participants, 44.9% were ever screened for cervical cancer.

However, only 10.4% of participants received timely repeated screening for cervical cancer.

Conclusions: The findings of the study reported low utilization of cervical cancer

screening among women in Nepal. We recommend a community-based educational

15

intervention to educate and empower women to increase the utilization of cervical cancer screening.

Oral session 3: Preclinical models and patient studies

INVOLVEMENT OF ADENOSINE TRIPHOSPHATE (ATP) IN HYPOXIA-INDUCED CHANGES IN THE DIAMETER OF LARGER AND SMALLER PORCINE RETINAL VESSELS EX VIVO

Charlotte Ernst, Department of Opthalmology, Aarhus University Hospital

T. Bek, Department of Opthalmology; C. Aalkjaer, Institute of Biomedicine (physiology); P.

Skov Jensen, Department of Opthalmology

Purpose: Retinal hypoxia (RH) is a key component of the pathophysiology of diabetic retinopathy with dysregulation of the microcirculation involving capillary nonperfusion and loss of capillary autoregulation. This dysregulation leads to progressive RH and subsequent vasodilatation. ATP is a purinergic vasoactive compound assumed to be involved in the RH-induced dilatation of the larger arterioles, but its involvement in the pathophysiological effects of pre-capillary arterioles and capillaries remains unknown.

Therefore, the purpose of the present study was to investigate the diameter response during RH alone and in the presence of antagonists to ATP-degradation and purinergic receptors.

Methods: Porcine superior hemiretinas (n=30) were mounted in a specially designed tissue chamber, and the diameter of retinal arterioles, pre-capillary arterioles and

capillaries were studied during RH with and without antagonists to the ATP-degradation (AOPCP), the P2-purinergic receptor (PPADS) and the A2B-adenosine receptor

(MRS1754).

Results: RH induced dilatation of both arterioles, pre-capillary arterioles and capillaries (p<0.01 for all comparisons). The dilatation of arterioles was blocked by both AOPCP, PPADS and MRS1754 (p<0.03 for all comparisons), whereas dilatation of pre-capillary arterioles and capillaries were blocked by PPADS (p<0.03) but not by neither AOPCP nor MRS1754 (p>0.50 for all comparisons).

Conclusion: RH-induced changes in the diameter of retinal vessels are regulated

differentially in larger arterioles, pre-capillary arterioles and capillaries. This may form the basis for selective interventions on the diameter of retinal vessels at different branching levels.

17

RESUSCITATION AFTER CARDIAC ARREST IN SEPTIC NEWBORNS;

RANDOMIZATION TO ADRENALINE VERSUS PLACEBO AND THE EFFECTS ON ROSC AND MARKERS OF CNS OUTCOME, A PIGLET STUDY

Hannah Brogård Andersen, Department of Paediatrics, Aarhus University Hospital, Denmark

Mads Andersen, Department of Paediatrics AUH; Lærke Hjøllund Hansen, Department of Paediatrics AUH; Ted Carl Kejlberg Andelius, Department of Paediatrics AUH; Bo Løfgren, Research Center for Emergency and Department of Cardiology AUH; Steffen Ringgaard, The MR Research Centre AUH; Kasper Jacobsen Kyng, Department of Paediatrics AUH;

Tine Brink Henriksen, Department of Paediatrics AUH Background

Guidelines for newborn life-support do not distinguish between different cardiac arrest (CA) aetiologies. The use of adrenaline is part of the resuscitating guidelines; however, adrenaline may not be the optimal treatment in sepsis associated CA (SA-CA), and may even cause poorer long-term outcomes. We aimed to investigate the effect of

adrenaline vs. placebo on 1) return of spontaneous circulation (ROSC), 2) time-to-ROSC, and 3) MRI/MRS markers of CNS outcome, in a piglet model of SA-CA.

Methods

Sepsis was induced in 30 newborn piglets by continuous infusion of lipopolysaccharide (LPS) from Escherichia coli. After four hours of LPS infusion hypoxia was induced by clamping the endotracheal tube until CA. CPR was commenced five min after CA and performed according to ILCOR 2015 guidelines. The piglets were randomized to either CPR + intravenous adrenaline or CPR + placebo (normal saline). MRI and MRS were performed 14 hours after resuscitation.

Results

LPS resulted in significant increased heart rate and lactate level and reduced pH, mean arterial blood pressure and white blood cells count in all piglets. A total of 29/30 piglets achieved ROSC. We found no difference in time-to-ROSC between piglets resuscitated with adrenaline compared to placebo (mean: 119 vs. 126 sec). MRI showed no

difference in brain edema (mean ADC: 429 vs. 495 10-6 mm2/s), oxygenation (mean BOLD T2*: 52 vs. 59 ms) or perfusion (mean ASL: 103 vs. 140 ml/min/100g).

Spectroscopy data are pending.

Conclusion

Resuscitation with adrenaline compared to placebo showed no difference in ROSC,

DECREASED AQP3 EXPRESSION IN PATIENTS WITH BILE ACID MALABSORPTION DUE TO RIGHT HEMICOLECTOMY

Jonathan Yde, Department of Biomedicine, Aarhus University

Helene M Larsen, Department of Surgery, Aarhus University Hospital & Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aarhus University Hospital

Janne L Fassov, Department of Hepatology and Gastroenterology, Aarhus University Hospital & Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aarhus University Hospital

Søren Peter German Jørgensen, Department of Hepatology and Gastroenterology, Aarhus University Hospital

Martin V Eivindson, Department of Internal Medicine, Regional Hospital in Horsens Klaus Krogh, Department of Hepatology and Gastroenterology, Aarhus University

Hospital & Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aarhus University Hospital

Hanne B Møller, Department of Biomedicine, Aarhus University

Background: Colon cancer patients treated with a right hemicolectomy (RHC) often suffer from bile acid malabsorption (BAM), a cause of chronic diarrhoea. BAM is poorly understood and various, simultaneous mechanisms may contribute; e.g. inhibited salt and water absorption, activated secretion and increased colonic motility. We

investigated colonic mRNA expression of water transporters in RHC patients with BAM and in healthy controls.

Methods: BAM was defined as 7-day-retention of 370kBq 75SeHCAT<15%. Diarrhoea was determined as >3 bowel movements/day with a consistency of 6–7 on the Bristol Stool Scale. Healthy controls were recruited among persons referred to endoscopy due to rectal bleeding, who had a normal endoscopy and no previous abdominal surgery.

Mucosal biopsies were taken 20–30cm from the anus. mRNA expression in isolated epithelial cells was analysed using RT-qPCR for aquaporin (AQP) 3, TGR5-targets Preproglucagon (GCG) and Peptide YY (PYY), and FXR-targets Short Heterodimer Partner (SHP) and Organic Solute Transporter β (OSTB).

Results: We included 15 RHC patients with BAM (median age: 70.0 years (range: 56–88), 10 males) and 20 controls (median age: 39.5 years (range: 25–69), 8 males). mRNA for AQP3 (P=0.014), GCG (P=0.045) and PYY (P=0.005) was significantly decreased in patients compared with controls. SHP and OSTB did not differ between patients and controls.

Conclusion: AQP3 mRNA was decreased in RHC patients with BAM compared with controls. Our results suggest that BAM is accompanied by changes in epithelial water transporters that may affect colon function. Whether this is a direct effect of bile acids or a secondary effect remains to be established.

19

SMOOTH MUSCLE CELL SPECIFIC DELETION OF SOX9 INCREASES NECROTIC CORE FORMATION IN ATHEROSCLEROSIS

Martin Mæng Bjørklund, Department of Clinical Medicine, Heart diseases, Aarhus University, Denmark and Spanish National Center for Cardiovascular Research (CNIC), Madrid, Spain

Morales D (2), Albarrán-Juárez J (1), Sørensen CB (1), Carramolino L (2), and Jacob Fog Bentzon (1,2)

(1): Department of Clinical Medicine, Heart diseases, Aarhus University, Denmark (2):Spanish National Center for Cardiovascular Research (CNIC), Madrid, Spain Background: Focal areas of cartilaginous metaplasia are frequent in murine atherosclerosis. They are produced by smooth muscle cells (SMCs) converting to a chondroid phenotype characterized by the expression of the chondrocyte master regulator SOX9. We set out to block the development of cartilaginous metaplasia by SMC-specific deletion of the Sox9 gene and analyze the effects on murine

atherosclerosis.

Methods: We generated mice with a floxed Sox9 gene and a transgene encoding

inducible Cre recombinase under a SMC-specific promotor. Atherosclerosis was induced using a recombinant AAV-vector encoding PCSK9 followed by a high-fat diet for 24 weeks.

Results: Recombination ratio of the floxed Sox9 gene was 82%. Plasma total cholesterol levels were elevated throughout the study period and, as anticipated, no difference in cholesterol burden was detected between the two groups. En face quantification of aortic lesion areas showed no difference between the two groups. Histological

examination of lesions in the brachiocephalic artery revealed similar plaque size, but the amount of cartilaginous metaplasia was reduced by 69% in mice with SMC-specific Sox9 deletion, showing the importance of SOX9 for SMC chondroid conversion. The reduced levels of metaplasia were accompanied by a 177% increased necrotic core size.

Conclusion: SOX9 expression in modulated SMCs is crucial for development of

intraplaque cartilaginous metaplasia and decreases necrotic core formation in murine brachiocephalic artery lesions. This suggests a protective role of cartilaginous metaplasia against necrotic core formation. Manipulating this pathway could be a future target for stabilizing atherosclerosis

RETINAL OXIMETRY DOES NOT PREDICT 12 MONTHS VISUAL OUTCOME AFTER ANTI-VEGF TREATMENT FOR CENTRAL RETINAL VEIN OCCLUSION: A MULTICENTRE STUDY

Signe Krejberg Jeppesen, Department of Ophthalmology, Aarhus University Hospital, Denmark

Martin Sin, Department of Ophthalmology, Olomouc, Czech Republic; Sveinn Hakon Hardarson, Department of Ophthalmology and Physiology,Reykjvavik, Iceland; Toke Bek, Department of Ophthalmology, Aarhus University Hospital, Denmark

Purpose: Central retinal vein occlusion (CRVO) entails retinal hypoxia that often causes visual impairment. It has been shown that oxygen saturation in larger retinal vessels correlate with the visual acuity at the time of diagnosis of CRVO but has no predictive value for the visual outcome in patients treated with anti-VEGF medication after 3 months. However, assessing the predictive value of retinal oxygen saturation after 12 months is essential because this is when the main restitution after CRVO occurs.

Methods: Retinal oximetry was performed in 117 patients referred with CRVO to three European centres. The correlation between oxygen saturation and visual acuity at

baseline and the predictive value of oxygen saturation in larger retinal vessels for the 12- month visual outcome after treatment with anti-VEGF medication were studied.

Results: In the affected eye, the oxygen saturation was significantly higher in the arterioles, significantly lower in the venules, and the arterio-venous (A-V) significantly higher than in the unaffected eye (p<0.001 for all comparisons). Correlations between best corrected visual acuity (BCVA) and oxygen saturations were moderate and

negative for arterioles (p<0.001), positive for venules (p=0.03) and negative for the A-V difference (p=0.001). BCVA, but not oxygen saturation or the other explanatory variables at baseline, contributed significantly to predicting BCVA after 12 months.

Conclusion: Retinal vessel oxygen saturation is affected in CRVO and saturation correlates with BCVA. However, retinal oximetry cannot replace measures of visual function as a predictor of visual outcome after 12 months of anti-VEGF treatment for CRVO.

21

A NOVEL PORCINE MODEL FOR CNV

Silja Hansen, Department of Biomedicine, AU

Anne Louise Askou, Department of Biomedicine, AU; Morten la Cour, Department of Ophthalmology, Rigshospitalet Copenhagen; Toke Bek, Department of Ophthalmology, Aarhus Univerity Hospital; Thomas Corydon, Department of Biomedicin, AU

Background

Ocular Gene therapy may be an attractive alternative to treat choroideal

neovascularization (CNV) in exudative AMD (eAMD). However, to bring this approach closer to application in humans, an animal model is needed. The purpose of this study was to develop a translational, reliable and reproducible porcine model for

experimental CNV.

Method

In the left eye of 17 pigs a serous detachment was induced by subretinal injection of saline. Subsequently, a laser burn was applied in the area of the detached neuroretina.

The right eye was treated with laser only. The effect was evaluated by optical coherence tomography (OCT), OCT-angiography and fluorescein angiography (FA) in vivo and histology after enucleation.

Results

For eyes treated with laser combined with retinal detachment, the neuroretina was undamaged and hyperreflective lesions compatible with CNV-formation were observed by OCT in 100% from day 7. For 80% of the eyes the presence of a CNV was confirmed by leakage on FA or as perfused choroidal vessels observed by OCT-A. For eyes treated with laser alone, hyperreflective lesions on OCT compatible with CNV formation were observed in 87% of the cases, but neuroretinal damage was observed in 100% of these.

Conclusion

Laser-induced experimental CNV in pigs can be produced with a high success rate, and neuroretinal damage can be prevented by a serous retinal detachment. Hence, this study may provide the foundation to evaluate novel treatment options for vascular retinal diseases, including eAMD, in a highly translational animal model for CNV.