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Page 1: Webinar event with COLLABORATE
Page 2: Webinar event with COLLABORATE

Webinar event with COLLABORATE

bmeg.upf

UPF Biomedical Engineering

BioTechTalks UPF

UPF Biomedical Engineering

https://eventum.upf.edu/56245/detail/biomedical-engineering-upf-congress-2021.html

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Institutions

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Index

Defences Schedule 4

Evaluation Comitee 10

Keynote Speakers 15

Abstracts 19

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Defences Schedule

Wednesday 30th June

Session 1: Keynote talks Chair: Pilar Rivera

Collaborate link for Session 1

Time Speaker Topic

9:00 – 9:40Carlos Blanco Vazquez.Entrepreneur & Investor

Como emprender con exito y no morir en el intento

10:00 – 10:40Carlos Abellan. Co-founder

and CEO of QusideQuside’s spin off journey

10:50 – 11:00 BIST: Barcelona Institute of Science and Technology

Round table QUAES

11:00 – 11:10 Clara Prats

11:10 – 11:15 Mario Ceresa

11:15 – 11:20 Nadia Perez & Alvaro Martınez

11:20 – 11:30 Juana Dıez

11:30 – 11:50 Discussion about strategies to fight COVID-19 pandemics

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Session 2: Mathematical modelling of biological systems Chair: Toni Ivorra

Collaborate link for Session 2

Time Speaker Topic

13:20 – 13:40 Mar Martınez MasStudy of the hydroelectrolitic mass transfer of calcium inhaemodialysis patients and its correlation to intradialytic

hypotension and parathormone unbalances

13:40 – 14:00 Quim Martı Baena The role of whole genome doubling in cancer evolution

14:00 – 14:20 Laura Orrit VinetsModelling immunogenicity in heterogeneous cancer cells under

the immune system action

14:20 – 14:40 Tomas Berjaga BuisanNeuronal basis of brain hypersynchronization in absence seizures:

a computational study

14:40 – 15:00 June Monge LorenzoPopulation dynamics of tumor-tumor interactions underlying

surgically triggered relapse

15:00 – 15:20 Ivan Dmitriy Ortiz Sanchez Mode and tempo of cultural evolution in video games

15:20 – 15:40 Sergi Marcoval MartınezAlteration in nerve function following electroporation: A

numerical modeling study of the electroporation conductanceeffect

Session 3: Innovation in medical imaging Chair: Jerome Noailly

Collaborate link for Session 3

Time Speaker Topic

16:00 – 16:20 Daniel Canadas Gomez3D Reconstruction of the Left Atrial Appendage from Multiple

2D Echocardiographic Data

16:20 – 16:40 Ana Harris MartınezBrain alterations between attention deficit/hyperactivity disorder

and autismspectrum disorder. A volumetric, structural andfunctional study

16:40 – 17:00 Elisabet Sorribes TorrentA novel approach to assess Alzheimer’s disease by using

radiomics in TgF3p-44-Ad rats

17:00 – 17:20 Laura Palacios Peral Hip joint space analysis for osteoarthritis diagnosis

17:20 – 17:40 Laura Perez SanchezAutomatic detection of new lesions in patients with multiple

sclerosis using the T1-w/T2-w magnetic resonance ratio

17:40 – 18:00 Marina Xicoira SerraAssesment of 4D aortic strain from 3D time- resolved MRI in

aortic aneurysms

18:00 – 18:20 Valentina Pasker GonzalezQuantification of Learning in an Augmented Reality Training

System Prototype for Minimally Invasive Fetal Surgeries

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Thursday 1st July

Session 4: Modelling of biological systems’ responses Chair: Javier Macia

Collaborate link for Session 4

Time Speaker Topic

9:00 – 9:20 Marian Iglesias BlancoIn-silico modelling of the deployment of left atrial appendage

occluder devices. A sensitivity analysis

9:20 – 9:40 Paula Casademunt PorteDevelopment of a patient-specific pipeline for the modelling of

mitral valve interventions with meshless techniques

9:40 – 10:00 Paula Domınguez Gomez Sensitivity analysis of haemodynamic modelling in coronaries

10:00 – 10:20 Marc Amilibia i SisonStudy of preoperatory field placement deformation to assess

oropharynx surgery

10:20 – 10:40 Mayra Loayza SaldanaScaling of a full three-dimensional knee joint model for the study

of osteoarthritis: towards developing a patient-specific model

10:40 – 11:00 Andreu Pascuet FontanetA computational model for collective chondrocyte behaviour in

osteoarthritis, in patient-specific biochemical micro-environments

11:00 – 11:20 Marıa Ballart VernetInfluence of bone in the biomechanical response of knee cartilage

in gait cycle of patients with osteoarthritis: A finite elementstudy

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Session 5: Neuroengineering Chair: Gemma Piella

Collaborate link for Session 5

Time Speaker Topic

12:00 – 12:20 Anna Rife MataThe role of orbitofrontal cortex in encoding spatial value and

working memory in a gambling decision-making task

12:20 – 12:40 Martın Esparza IaizzoSleepBCI: a platform for sleep quality assessment and memory

enhancement based on automatic scoring

12:40 – 13:00 Justo Montoya GalvezSeizure prediction and epileptogenic zone definition through

pre-ictal state analysis

13:00 – 13:20 Aina Maull MiquelEngineered Graphene for Neural Interfaces - Study of the

Functional Stability in Activated Graphene-based ElectrodesAfter Sterilization with Ethylene Oxide

13:20 – 13:40 Sergi Navarro GuimeraAuricular transcutaneous vagus nerve stimulation device in theform of a pod: A first step towards chronic non-invasive vagus

nerve stimulation in mice

13:40 – 14:00 Sandra Gonzalez Alonso Occipital alpha oscillations and sex differences

Session 6: Artificial Intelligence Chair: Baldomero Oliva

Collaborate link for Session 6

Time Speaker Topic

15:00 – 15:20 Olalla Aramburu CabadaEnhancing surgeon action detection in robot-assisted minimally

invasive surgery

15:20 – 15:40Daniel Cantabella Vives de

la CortadaMachine Learning-based prediction of optimal LAAO device

settings

15:40 – 16:00 Angel Bazan Castello Use of unsupervised techniques for brain MRI stratification

16:00 – 16:20 Berta Calm SalvansDevelopment of fully automated echocardiographic data

interpretation technique

16:20 – 16:40 Roi Carrera BooAutomatic detection and analysis of visual patterns and

movement of lampreys for neurological investigation

16:40 – 17:00 Adolfo Aguirrezabal BlancoSegmentation and classification of animal behavior from tri-axial

accelerometry recordings

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Friday 2nd July

Session 7: Advanced technologies in healthcare Chair: Jordi Garcıa-Ojalvo

Collaborate link for Session 7

Time Speaker Topic

9:00 – 9:20 Juan Manuel Dıaz GimenezNanoparticle-assisted ROS production towards photothermal

treatement of cancer

9:20 – 9:40 Eduard Sune MoroteRetroviral Directed Evolution Platform for Mammalian Gene

Therapy Tools

9:40 – 10:00 Maria Pol CrosCutibacterium acnes extracellular vesicles: characterization and

modulation of the skin immune response.

10:00 – 10:20 Silvia Perez GarcıaPharmacological experiment on neurodegeneration in mature

trisomic mouse models

10:20 – 10:40 Marcos Chic CobrecesDevelopment of an open-source, wireless and implantable vagus

nerve stimulator for preclinical studies in mice

10:40 – 10:50 BREAK

10:50 – 11:10 Judith Martınez GonzalezGene expression remotely controlled by an electronic device

using a thermal interface

11:10 – 11:30 Jaume Puig Costa-JussaEngineering Escherichia coli for survival in outer space

conditions. Enhancing bacterial resistance to extreme levels ofradiation, temperature, and pressure

11:30 – 11:50 Daniel Lechuga MorenteA first study for the establishment of a source of vitamin B12 as

of the genetic modification of the cyanobacteria Arthrospiraplatensis

11:50 – 12:10 Miriam Caravaca RodrıguezContinuous Vibrio cholerae detection and quantification through

a biosensor with genetically engineered Escherichia coli

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Session 8: Medical innovation Chair: Nuria Brunet

Collaborate link for Session 8

Time Speaker Topic

13:20 – 13:40Martina de la Varga

RodrıguezNanoLuxe: a market analysis, pricing policy and regulatory

affairs for an anti-counterfeit company based on nanotechnology

13:40 – 14:00 Andrea Enero BalfagonBusiness Plan To Commercialize A Live Biotherapeutic Product

For Acne Treatment

14:00 – 14:20 Marta Benavides LasalaBusiness plan for the creation of a capacity and occupancy

tracking smartphone app: EasyCount

14:20 – 14:40 Arnau Masdevall LaraDevelopment and evaluation of an accessible mobile applicationto create intergenerational pairs and connect with agricultural

initiatives

14:40 – 15:00 Adria Moran Riera Implementation of a healthcare innovation platform: SymBio

15:00 – 15:20 David Agullo GonzalezBusiness Plan for introducing to the market a Body Dehydration

Sensor

15:20 – 15:40 Mitar Nikolic JovanovicDesign and development of an active balancing stick for

enhancement of mobility

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Evaluation Comitee

BT Final Evaluation Comitee

Pilar Rivera

Toni Ivorra

Jerome Noailly

Javier Macia

Gemma Piella

Baldomero Oliva

Jordi Garcıa-Ojalvo

Nuria Brunet

Wednesday 30th June

Session 2: Mathematical modelling of biological systems Chair: Toni Ivorra

Collaborate link for Session 2

Time Reviewer

13:20 – 13:40 Jordi Garcıa-Ojalvo

13:40 – 14:00 Frederic Bartumeus

14:00 – 14:20 Blai Vidiella

14:20 – 14:40 Pau Clusella

14:40 – 15:00 Frederic Bartumeus

15:00 – 15:20 Blai Vidiella

15:20 – 15:40 Enric Perera

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Session 3: Innovation in medical imaging Chair: Jerome Noailly

Collaborate link for Session 3

Time Reviewer

16:00 – 16:20 Miguel Angel Gonzalez

16:20 – 16:40 Miguel Angel Gonzalez

16:40 – 17:00 Jose Carlos Paciente

17:00 – 17:20 Mirella Lopez

17:20 – 17:40 Miguel Angel Gonzalez

17:40 – 18:00 Lydia Dux

18:00 – 18:20 Gemma Piella

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Thursday 1st July

Session 4: Modelling of biological systems’ responses Chair: Javier Macia

Collaborate link for Session 4

Time Reviewer

9:00 – 9:20 Andy Olivares

9:20 – 9:40 Eduardo Soudah

9:40 – 10:00 Andy Olivares

10:00 – 10:20 Carlos Ruiz

10:20 – 10:40 Simone Tassani

10:40 – 11:00 Miguel Angel Gonzalez

11:00 – 11:20 Simone Tassani

Session 5: Neuroengineering Chair: Gemma Piella

Collaborate link for Session 5

Time Reviewer

12:00 – 12:20 Gabriela Mochol

12:20 – 12:40 Salvador Soto-Franco

12:40 – 15:00 Ricardo Zucca

15:00 – 15:20 Javier Macia

15:20 – 15:40 Ruben Moreno

15:40 – 14:00 Ruzzoli, Manuela

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Session 6: Artificial Intelligence Chair: Baldomero Oliva

Collaborate link for Session 6

Time Reviewer

15:00 – 15:20 Simone Tassani

15:20 – 15:40 Gemma Piella

15:40 – 16:00 Miguel Angel Gonzalez

16:00 – 16:20 Patricia Garcıa

16:20 – 16:40 Roberto de la Torre

16:40 – 17:00 Jeome Noailly

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Friday 2nd July

Session 7: Advanced technologies in healthcare Chair: Jordi Garcıa-Ojalvo

Collaborate link for Session 7

Time Reviewer

9:00 – 9:20 Can Xiao

9:20 – 9:40 Avencia Sanchez-Mejıas

9:40 – 10:00 Santos, Javier

10:00 – 10:20 Pol Picon

11:00 – 11:20 Albert Comerma

10:40 – 10:50 BREAK

10:50 – 11:10 Marta Puig

11:10 – 11:30 Javier Santos

11:30 – 11:50 Javier Santos

11:50 – 12:10 Oriol Gallego

Session 8: Medical innovation Chair: Nuria Brunet

Collaborate link for Session 8

Time Reviewer

13:20 – 13:40 Bernat Mir

13:40 – 14:00 Rafael Manzanera

14:00 – 14:20 Rafael Manzanera

14:20 – 14:40 Rafael Manzanera

14:40 – 15:00 Javier Macia

15:00 – 15:20 Jerome Bernard Noailly

15:20 – 15:40 Toni Ivorra

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Keynote Speakers

Carlos Abellan

Quside’s spin off journey

Carlos Abellan is the co-founder and CEO of startup Quside, a technology spin-off that designs and produces quan-tum components for any connected device. He is also a co-founder and NED of startup Finboot, which developsblockchain technology for businesses. He has a doctorate in photonics from the Institute of Photonic Sciences ofCatalonia (ICFO), where he focused his research in the field of quantum technologies applied to cybersecurity andsupercomputing. He has published several scientific papers in international magazines and conferences, as well asbeing the inventor of several patents. His research has led to the creation of the spin-off Quside, which brings quan-tum technologies to the market. As a result of his research and his entrepreneurship, he has been awarded severalawards, including the MIT Innovators Under 35 Europe and the Pioner Award from CERCA.

Carlos Blanco Vazquez

How to become an entrepreneur and not die trying

(Barcelona, 1968) Carlos Blanco is an entrepreneur and private new technologies investor. Winner of the Best En-trepreneur Award in Spain for the X Pyme Awards for Expansion and Ifema; And Best Business Angel 2014 forthe AEBAN Awards.In 2011 he founded Akamon Entertainment, a traditional social gaming and casino company, aleader in Southern Europe and Latin America, which he sold at the end of 2015, becoming one of the most importantexits of the year in Spain. He recently founded Nuclio Venture Builder and finished the activities of Grupo Itnet. Hehas also launched the Encomenda Smart Capital, to manage all his investments, which since 2005 amounted to 70companies. He is the editor of the blog of reference for the entrepreneurs carlosblanco.com and writer of the book”The main mistakes of the entrepreneurs” (Los principales errores de los emprendedores).

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QUAES Round Table ParticipantsClara Prats

Clara Prats Pons received a BSc in Physics from the Universitat de Barcelona (UB) in 2002. She completed andobtained a Ph.D. in Computational and Applied Physics from the Universitat Politecnica de Catalunya in 2008. Clarais an associate professor at UPC and a postdoctoral fellow at the Computational Biology and Complex Systems group(BIOCOMP-SC). Moreover, she is the computational model responsible at the Centre de Medicina Comparativa iBioimatge de l’Institut de Recerca en Ciencies de la Salut Germans Trias i Pujol (IGTP). Clara focuses her researchon infectious diseases mathematical modelling, especially tuberculosis and recently the well-known COVID-19. Shecurrently collaborates with the European Commission in daily analysis and prediction reports for multiple countries.Recently she has been awarded the Matematiques I Societat 2021 award for her contribution to COVID-19 analysisand mathematical modelling.

Juana Dıez

Juana Marıa Dıez Anton began her studies in Biology in 1985 at the University of Seville, Spain. In 1990 she did herdoctoral thesis at the Molecular Biology Center of the Autonomous University of Madrid, where she specialized invirology. From 1993 to 2000, Juana was a postdoctoral researcher, first at the Higher Council for Scientific Research(CSIC) within the department of phytopathology in Murcia, and then at the Institute of Molecular Virology at theUniversity of Wisconsin-Madison, USA. In 2006 she began working as a guest professor at the Institute of Virologyat the University of Saarland, Germany, and currently works as a full professor at the Faculty of Life and HealthSciences at Universitat Pompeu Fabra (UPF), and as principal investigator in the molecular virology laboratory of theDepartment of Experimental Sciences and Health (DCEXS). In 2016 she was awarded the ICREA Academia awardand the following year she was named collegiate of honor by the Col·legi de Biolegs de Catalunya.During her entire career, Juana has participated in the publication of many articles related to virology. Her latestpublication, carried out together with a group of doctors and researchers from Hospital del Mar, the Hospital delMar Institute for Medical Research and UPF, studies the effect of zinc levels with the expansion capacity of theSARS-CoV-2 coronavirus, by means of in vitro techniques.

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Mario Ceresa

Mario Ceresa received a BSc in Electronic Engineering and a MSc in Biomedical Engineering from Politecnico of Milan,Italy, in 2008. He completed his doctoral thesis about the automatic detection of Chronic Obstructive PulmonaryDisease at Navarra University in 2012. Mario Ceresa worked in Alma IT Systems before joining the Simulation,Imaging and Modelling for Biomedical Systems (SIMBIOsys) group as a post-doctoral researcher and becoming anassociate professor at Universitat Pompeu Fabra (UPF). He has participated in several research projects, includingthe European project HEAR-EU, mainly working on biomechanical and electrical simulations of the inner ear. Heprimarily focuses his research on the medical image analysis, biomechanics, and finite element methods field.Moreover, he is currently leading the Interactive Policy Explorer for Planetary Wellbeing project. There, he isdeveloping mathematical epidemiologic models for COVID-19, among other things. He is a reviewer for PlosOne,Academic Radiology, Medical Image Analysis, Transaction of Medical Image journals and contributes to MICCAI,CARS, ISBI, and ICNA conferences. Since 2020, he holds an Executive MBA from IESE Business school.

Nadia Perez & Alvaro Martınez

MASKIN Care is a new and young biotech company that looks for real solutions to the current health emergency,through the development of high-tech innovative health products.

The MASKIN research group won the overall “Enginy contra la COVID-19” contest with the innovative project’Papiro Masks-Medicine & Engineering Progress’, promoted and funded by the Universitat Pompeu Fabra el ConsellSocial, and the Catedra QUAES & Excelencia Marıa de Maeztu, which promotes projects for the development of toolsand protocols that help in the global fight against the spread of the coronavirus. Currently MASKIN commercializeswith the design of an innovative transparent mask that allows the visualization of the user’s mouth with the intentionof allowing a correct reading of the lips to preserve gestural and visual communication and to make life easier forpeople with hearing problems. The group achieved The Collider GenCat grant for speeding up the start-up and ownsa patent. Their main goal now is to consolidate the business by extending their product’s portfolio by mixing puretechnology and healthcare.

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Nadia Perez, a 22-year-old girl from Barcelona, is a medical student at the Universitat Pompeu Fabra (Barcelona).The co-founder of MASKIN currently holds the position of Chief Operating Officer at MASKIN Care.

Alvaro Martınez is a 20-year-old Soriano student with a degree in Biomedical Engineering at Universitat Pom-peu Fabra (Barcelona). Alvaro is co-founder, sales chief and expansion delegate at MASKIN Healthcare, dedicatedto the deep search of solutions in clinics.

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Abstracts

Adolfo Aguirrezabal Blanco

Segmentation and classification of animal behavior from tri-axial accelerometry recordings

Supervisor(s) Referee 1 Referee 2

Cos, IgnasiGonzalez-Solıs, Jacob

Noailly, Jerome Tassani, Simone

Abstract: To this day, the behavior of many animal species is largely unknown to us due to the enormous difficultiesinvolved in observing them in their natural state. Accelerometry provides a promising way to overcome this challenge,allowing us to obtain detailed information about the movement of different animal species with a high temporalresolution. In the present work we propose a pipeline for the generation of ethograms (catalogues of the differentbehaviors displayed by a species) across different temporal scales using tri-axial accelerometry recordings from a speciesof seabird, the Red-Billed Tropicbird (Phaeton Aethereus). This pipeline consists in a method for the segmentationof potential behaviors from acceleration signals that employs a window of adaptive size, (2) a method for groupingand aligning those segments based on their maximum correlation, resulting in groups of segments that correspond tobehaviors typically employed by the species and (3) a Recurrent Neural Network that is trained using these groups inorder to be able to classify previously unobserved recordings. Finally, we demonstrate the usefulness of this methodby attempting to answer questions about the ecology and behavior of our subject species using the behaviouralclassification generated by this pipeline.

Keywords: Tri-axial accelerometry, Behavioural classification, Movement ecology, Recurrent Neural Networks

Adria Moran Riera

Implementation of a healthcare innovation platform: SymBio

Supervisor(s) Referee 1 Referee 2

Quesada, Rita Macia, Javier Camara, Oscar

Abstract: In these last years, medical technology innovations have fundamentally transformed the health care system.In this complex background, the need of a platform that connects real needs from daily routine in hospitals or patientswith companies and students to collaborate in the execution, development and implementation of the solution tothe problems identified, becomes evident. In this project the practical development of SYMBIO is performed, a bothweb and mobile app, that enhances open innovation and communication between research groups. Results showpromising generalized acceptance and validation of the idea and methodology implemented.

Keywords: Webpage, App, Open Innovation, Entrepreneurship, Healthcare

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Aina Maull Miquel

Engineered Graphene for Neural Interfaces - Study of the Functional Stability in ActivatedGraphene-based Electrodes After Sterilization with Ethylene Oxide

Supervisor(s) UPF Tutor Referee 1 Referee 2

Garrido, Jose AntonioAndrzejak, Ralph Gregor

Andrzejak, Ralph Gregor Macia, Javier Montbrio, Ernest

Abstract: A neural implant is a device placed in the central or peripheral nervous system to interact with neuronsthrough electrical pulses to recover functionalities and treat an ever-increasing list of neurological disorders. Materialscience allows to keep pushing forward the boundaries of knowledge by providing new materials that can improvethe resolution, the signal reliability and be safer for patients. This is the case of EGNTIE (Engineered graphene forneural interfaces), a new technology based on a carbon-based material.

With this promising technology have been possible to miniaturize the neural implants to the micrometric scale.However, it has been never tested in humans. This thesis aims to assess the electrochemical consequences that maybe altered after a sterilization process with Ethylene Oxide.

22 devices from 3 different designs were distributed in two experimental phases. During the first phase it wasstudied the functionalization of EGNITE electrodes. In the second phase, 11 devices were sent to sterilize by per-forming several electrochemical characterizations, before and after the process.

The obtained results were analysed with a software created for this thesis, which allow us to get conclusions atdifferent statistical levels. In two different design, the results were not conclusive since the source of error waslocalized before the sterilization process. Nevertheless, results from the last design proves that the electrochemicalproperties were not modified beyond the accepted range and the functionality was kept after the sterilization process.However, a second round of experiments is needed to statistically verify the lack of electrochemical changes at theelectrode level.

Keywords: Graphene, Electrochemical Activation, Ethylene Oxide

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Ana Harris Martınez

Brain alterations between attention deficit/hyperactivity disorder and autism spectrum disorder. Avolumetric, structural and functional study

Supervisor(s) UPF Tutor Referee 1 Referee 2

Pareto, DeborahPiella, Gemma

Camara, Oscar Gonzalez, Miguel Angel Martı, Gerard

Abstract: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevel-opmental disorders that commonly affect children at early age. Both display a significant heterogeneity as well assharing high rates of comorbidity, suggesting that new clinical biomarkers are needed to complement the diagnosticprocess.

In this study we used structural and functional magnetic resonance images (3D T1-weighted, Trio Siemens 3.0T) from 163 patients (33 ASD, 84 ADHD, 23 ASD + ADHD) and 23 healthy control (HC) were analysed fordifferent analysis, such as voxel-based morphometry (VBM), cortical thickness estimation and functional/structuralconnectivity approaches.

Besides traditional VBM studies, a new approach has been developed to quantify the degree of heterogeneity incortical thickness through a z-score. For that purpose, regional brain cortical thickness measures were used compar-ing ASD, ADHD and ASD + ADHD with HC. Patients with a score higher than ± 2 SD were considered. Resultsfor each group show that, for a specific region, differences were presented in the 50% of the sample. In the case offunctional connectivity, differences were found in the sensorimotor network in ASD and ADHD, and in the cerebellarnetwork for ADHD, when compared with HC.

The results obtained put forward that more studies are needed to understand better the role of the heterogene-ity in these disorders and identify specific patterns in each subgroup for a future classification role in the diagnosis.

Keywords: MRI, voxel-based morphometry, Autism spectrum disorder, Attention deficit/hyperactivity disorder,cortical thickness

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Andrea Enero Balfagon

Business Plan To Commercialize A Live Biotherapeutic Product For Acne Treatment

Supervisor(s) Referee 1 Referee 2

Soler, Carles Manzanera, Rafael Taule, Carles

Abstract: Acne vulgaris is the eight most common skin disease spread throughout the world, affecting approximately9.4% of the world’s population with the highest prevalence in adolescents. Although several factors are involved inits development, the exact cause of the process remains unknown.

Current treatment approaches for acne are effective but have some complexity and come with undesirable sideeffects, some of which are severe. Furthermore, no meaningful novel products have been brought to market withinthe last decade. Using advances in technology, researchers have increased what is known about acne and its phys-iopathology. This better understanding of the disease has led to the identification of innovative and safer treatmenttargets. In the recent years, the Translational Synthetic Biology research group from UPF has started a new lineof research to genetically modify the skin bacteria (specifically Cutibacterium Acnes) to modulate changes in thesebaceous secretion. Their objective is to generate a platform to combine gene therapy and probiotic treatments, inorder to produce different therapeutic applications, being one of their main target acne vulgaris.

In this final project, a business plan will be designed to assess the viability of a company dedicated to acne treatment,based on the UPF research. The aim of this project is to provide a clear path for the researchers that want to enterthe world of entrepreneurship with their innovation. The business plan consists on the description of the idea, amarket study on the sector, evaluation of the clinical and regulatory framework, the business model and the plans ofthe different areas of the company: operations, marketing, finance, human resources and fundraising. At the end ofthe study, the viability of the proposed business is verified.

Keywords: Business Plan, Entrepreneurship, Therapeutics, Acne, Microbiome,

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Andreu Pascuet Fontanet

A computational model for collective chondrocyte behaviour in osteoarthritis, in patient-specificbiochemical micro-environments

Supervisor(s) Referee 1 Referee 2

Noailly, JeromeSegarra-Queralt, Marıa

Gonzalez, Miguel Angel Pinero, Janet

Abstract: Osteoarthritis (OA) is a common disease characterized by articular cartilage degradation that leads tostiff and painful joints. Its pathophysiology is not well understood, and researchers and clinicians struggle to quantifythe relative influence of mechanical and biochemical factors on the dysregulation of cartilage chondrocytes activitythat favours catabolic compared to anabolic processes. In sillico approaches can address this issue, as they canintegrate and systematically interpolate both clinical and experimental data. On the one hand, cartilage mechanicsand multi-physics have been described through numerical finite element models and simulations. On the other hand,network modelling (NM) has proven to be useful to simulate semi-quantitatively the metabolic activity of a singlechondrocyte. But it is still difficult to interpolate tissue mechanics and single-chondrocyte metabolic regulationmodels. We hypothesize, hereby, that it is possible to simulate interacting NM through agent-based modelling(ABM), to grasp relevant cell-cell phenomena that might not be apparent when just considering one NM at thecell scale. A multicellular model was developed through ABM, to simulate inter-chondrocyte paracrine activity anddynamic cell collective behaviour in a representative cartilage volume, through the cooperation of several NM at thecell level. Both literature and experimental data, including mRNA expression of cartilage explants and synovial fluidprotein quantification by immunoassays in OA patients, were used to explore different model components and theirinteractions. Results are expected to improve the interpretation of OA states depending on the initial metabolicenvironment of the simulations. These states are expected to be characterized by specific concentrations of proteinsin the simulated tissue volume plus semi-quantitative data proportioned by the chondrocytes. All in all, the modelshould translate the single-cell semi-quantitative results to quantitative data so that mechanical models could thenbe coupled at the cellular level.

Keywords: Knee OA, inflammation, articular cartilage, network modelling, agent-based modelling

Angel Bazan Castello

Use of unsupervised techniques for brain MRI stratification

Supervisor(s) Referee 1 Referee 2

Masias, MireiaPiella, Gemma

Gonzalez, Miguel Angel Urru, Andrea

Abstract: This work is going to focus on first episode psychosis. Diagnostic procedures for the identification andclassification of the disorder are being improved recently with the introduction of Deep Learning in the analysis of thepatient’s MRI and other variables with clinical significance. The objective of this project is to process these variableswith unsupervised Machine Learning techniques in order to identify certain patterns and obtain some accuracy in theclassification between stages inside the disorder. To accomplish the objective, we obtained several variables from theMRI images of the subjects. The resulting database was processed with different techniques such as dimensionalityreduction algorithms and Autoencoders.Different resulting clusters are composed by patients that share a particular characteristic but the exact variables thatdifferentiate the clusters is currently unknown.

Keywords: First Episode Psychosis, Clustering, Dimensionality Reduction, Unsupervised Machine Learning,Variational Autoencoders

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Anna Rife Mata

The role of orbitofrontal cortex in encoding spatial value and working memory in a gamblingdecision-making task

Supervisor(s) Referee 1 Referee 2

Moreno, RubenFerro, Demetrio

Mochol, Gabriela Hyafil, Alexandre

Abstract: Several studies have widely shown how neurons in the orbitofrontal cortex play a crucial role in encodingthe value associated to alternative options in reward-directed behavior. This has led to a wealth of knowledge aboutthe phenomenology of high order cognitive processes, including working memory and decision making. Despite this, itremains unclear how the integration and comparison between these offers is made in our brain cells. In asynchronousoffer presentation tasks, the orbitofrontal cortex was recently suggested to be involved in working memory functionsto favor the coding and maintenance of the estimated value of a firstly presented offer and so that it could becompared to the estimated value of the later presented one. Importantly, it is yet to be assessed what is the roleof perceptual cues such as the order of offers presentation and/or their spatial location. This dissertation progresson these research questions, by analyzing and modelling behavioral, neuronal and eye tracking data recorded fromtwo macaques performing a gambling decision-making task. With the aim of understating how the brain overcomesthe perceptual decision-making, we applied machine learning techniques such as logistic regressions and generalizedlinear models to determine which relevant parameters influence and predict animal’s choices on a trial-by-trial basis.It is hereby shown how subjects solved the task by successfully deducing the expected value of the two alternativereward offers, with clear evidence for risk seeking attitude. The analysis of eye data allowed to investigate and sortout how reward choices were tightly related to the fraction of time spent at the respective offer sides. Interestingly,monkeys seemed keen on looking at best offer side even during blank screen time periods, allowing to investigate thefunctional role of the orbitofrontal neural firing. In particular, differences in the tuning properties of neurons towardseither left or right offer suggested a spatial selectivity role of the orbitofrontal cortex, together with its centrality inreward-based choice.

Keywords: Computational Neuroscience, Orbitofrontal Cortex, Economic Decision-making, Working memory,Neuronal Encoding

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Arnau Masdevall Lara

Development and evaluation of an accessible mobile application to create intergenerational pairsand connect with agricultural initiatives

Supervisor(s) Referee 1 Referee 2

Fradera, Carles Manzanera, Rafael Leihner, Dietrich

Abstract: Cities concentrate more than half the total population on Earth and by 2050 two out of every three peoplein the world are expected to live in urban areas. Furthermore, most of the vegetable products we consume are the resultof an agroindustrial system of production that is responsible for around 50% of worldwide greenhouse gas emissions.The present pandemic shows that sustainable ways to produce food are essential to avoid undesired transmissionof diseases and that social isolation can be very detrimental to our wellbeing. Apart from its environmental andmental health benefits, urban agriculture represents an opportunity to improve nutrition and food security in urbanareas. With a growing gentrification and life expectancy it is important to implement strategies that allow cities toreduce their environmental footprint and people to be more connected with nature and their communities. In orderto take advantage of the benefits of intergenerational interactions and the increasing adoption of technology amongolder adults, in this work an accessible mobile application prototype to create intergenerational connections betweenpeople interested in agriculture and nearby initiatives that promote the connection with nature was conceptualized anddeveloped with the feedback of 10 volunteers ranging from 22 to 80 years old. Moreover, the potential acceptabilityand perceived usefulness of the platform was evaluated with a survey of 50 people comprising 10 participants of everysocietal generation. Although the prototype still needs further improvement and a deeper evaluation of its usefulnessshould be made, most older adults in this study still faced difficulties with the accessible design but reckoned theywould be able to use it if taught how to do so. Additionally, 66% of the participants in the survey perceived thatusing the platform would improve their quality of life and 58% expressed will to use it if available.

Keywords: Mobile application, Intergenerational connections, Accessible design, Urban agriculture, React Native

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Berta Calm Salvans

Development of fully automated echocardiographic data interpretation technique

Supervisor(s) Referee 1 Referee 2

Camara, OscarJimenez-Perez, Guillermo

Vilades, DavidLeta, Ruben

Moustafa, Abdel H.

Garcıa, Patricia Gomez, Alberto

Abstract: The segmentation of cardiac structures is a routine task performed by clinicians, and it is done by man-ually delineating each part to be able to extract indices to help in the diagnosis. Over the last years, deep learningtechniques had been studied to automatize the whole echocardiogram interpretation process, including the view recog-nition, the segmentation, and the index extraction parts. In the study, we developed and validated a convolutionalneural network architecture, based on U-Net, for 2D echocardiogram multi-structure segmentation. The dataset usedfor training was CAMUS, an open-source dataset from 500 patients that includes annotations of the left ventricle,the myocardium, and the left atrium. The results obtained showed a mean Dice coefficient of 0.93, 0.86, and 0,89on the three structures respectively. Moreover, the model was evaluated qualitatively using the EchoNet-Dynamicdataset and real-world clinical data from Hospital de Sant Pau. For the last one, ground-truth images were generatedand validated to obtain quantitative metrics to evaluate the model performance.

In addition, the Doppler echocardiograms from the clinical data were used to evaluate a view-recognition modelfor Doppler classification. To analyze the results and detect the most common errors generated due to intervariabilitybetween datasets and the intravariability between the different echocardiogram view plans.

Keywords: Echocardiography, Segmentation, Deep learning, U-Net, CAMUS

Daniel Lechuga Morente

A first study for the establishment of a source of vitamin B12 as of the genetic modification of thecyanobacteria Arthrospira platensis

Supervisor(s) Referee 1 Referee 2

Guell, Marc Santos, Javier Mogas, Sira

Abstract: Cobalamin de novo synthesis appears to be restricted solely to some bacteria and archaea. In humans,this nutrient is usually acquired through the consumption of animal products. However, it can lead to a vitamin B12deficiency in people with plant-based lifestyle where the consumption of animal products is minimal. Therefore, weinvestigated in this study the possibility of creating a source of cobalamin from cyanobacteria, a photosynthetic andnitrogen-fixing blue-green algae. Arthrospira platensis, an edible cyanobacteria, can produce a pseudovitamin B12but lack enzymes involved in the production of the active variant which can be metabolized by humans and usedas a vitamin B12 source. Therefore, we compared the metabolic pathways of the pseudovitamin B12 synthesized inthe cyanobacteria Arthrospira platensis with the canonical synthetic pathways of vitamin B12 discovering that thecobT, cobC and cobS genes, key players in the binding of the lower ligand characteristic of vitamin B12, are the mainabsence present in the metabolic pathways of cyanobacteria. Subsequently, we designed a transformation systembased on Tn5 transposition that could bridge the differences between the two pathways. For this purpose, the genescblT and cblS, from the thermophilic bacillus Geobacillus (G.) Kaustophilus with the ability shown to substitute theaction of the cob genes in other species, has been selected to constitute the Tn5 transposon, as well as a resistanceto the antibiotic spectinomycin.

Keywords: Synthetic biology, Cyanobacteria, Vitamin B12, Tn5 transposition

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Daniel Canadas Gomez

3D Reconstruction of the Left Atrial Appendage from Multiple 2D Echocardiographic Data

Supervisor(s) Referee 1 Referee 2

Camara, Oscar Gonzalez, Miguel Angel Paulsen, Rasmus

Abstract: Clot formation in the left atrial appendage (LAA) is a very common problem in patients with previouspathologies, such as atrial fibrillation (AF), which can lead to fatal consequences. In these patients, computer simula-tions can help predicting possible risks and assessing clinicians’ decisions. However, to perform LAA fluid simulations,volumetric images are necessary, from which the 3D structure can be segmented. Computed tomography (CT) scansare useful for this, but due to their high cost, high dose of radiation or simply because they are not always availablein every hospital, they are performed in a minimum number of patients. On the other hand, echocardiography is acommon technique, which is done routinely in AF patients. The objective of this project is to use deep learning (DL)techniques to reconstruct a 3D model of the left atrial appendage from single multi-view echocardiography images.The hypothesis to be tested is that a correctly trained DL algorithm can learn to reconstruct a 3D structure fromultrasound images, while keeping the most important details from each of the input views, thus obtaining a realisticenough model.A modification of classic variational autoencoders was considered an optimal approach for the task of 3D recon-struction in echography images. The performance of the network was evaluated by computing the Dice Score andHausdorff distance, and comparing fluid simulation results between ground-truth and reconstructions. The resultsdemonstrate the potential of DL and variational autoencoders in reconstruction problems and open the possibility ofcheaper and more efficient stratification method for patients with AF.

Keywords: Deep Learning, Computer vision, Variational autoencoder, Ultrasound, Left atrial appendage

Daniel Cantabella Vives de la Cortada

Machine Learning-based prediction of optimal LAAO device settings

Supervisor(s) Referee 1 Referee 2

Camara, OscarMill, Jordi

Piella, Gemma Weng, Yu

Abstract: Atrial fibrillation (AF) is the most common heart arrythmia in humans. Around 99% of thrombi areformed in the left atrial appendage (LAA) due to non-valvular AF. High risk of clot formation is usually treated byoral anticoagulation (OAC), but patients contraindicated to OAC, usually need an alternative treatment consisting onthe implantation of a left atrial appendage occlusion (LAAO) device. The uniqueness of the LAA morphologies andthe wide possibility of selection between different LAAO device models and sizes make this process very dependenton the doctor’s experience.We hypothesize that a machine learning-based algorithm aimed at the prediction of the optimal configuration of aLAAO device for a given left atria (LA) geometry could be helpful for the pre-operative planning.This involves the collection of a large amount of data where different morphological measurements taken from realpatients are considered and the creation of a ground-truth database by deploying the devices with the use of a virtualplatform called VIDAA.

Keywords: Atrial fibrillation, Machine Learning, Left atrial appendage, Device configuration, Morphologicalparameters

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David Agullo

Business Plan for introducing to the market a Body Dehydration Sensor

Supervisor(s) Referee 1 Referee 2

Soler, Carles Noailly, Jerome Brunet, Nuria

Abstract: Dehydration affects human physiology in many ways. Dehydration concentrations of as little as 2% bodyweight are noted to cause significant decrease in physical performance. One of the main reasons of introducing adehydration sensor to the market is to satisfy the necessities of ordinary white-collar workers, students, and otherless-active groups. They can often be too occupied by their schedules to actively think about their hydrationstatus. Because thirst is not an accurate gauge of dehydration, the problem can be especially deceptive in less-activeindividuals. However, most of the sensors available are not suitable to be adapted to sedentary monitoring wheresweat has not a main role in detecting levels of dehydration. There exists a demand that is not been covered enoughof hydration sensor systems that does not require perspiration. Thus, our idea tries to address not sweat dependentdehydration through bio-impedance analysis, which is a technique that has the advantage of being directly relatedto the total volume of water in the body (Total Body Water).After doing a market study, contemplating and developing an operations and financial plan, we could see that theidea of bringing Sensewater to the market could be viable. We decided on a sales system focused on distributorsand wholesalers where our product can be sold online and to different institutions or companies such as pharmacies.Regarding its manufacture, we opted for a location in the city of Shenzen, China. Finally, after doing a financialstudy on this business idea, we were able to contemplate its viability. After taking into account the income receivedfrom part of the stipulated number of sales obtained in a period of 5 years.

Keywords: Dehydration, wearable, sensor, monitoring, necessity, viability, market, Total Body water

Eduard Sune Morote

Retroviral Directed Evolution Platform for Mammalian Gene Therapy Tools

Supervisor(s) Referee 1 Referee 2

Guell, MarcIvancic, Dimitrije

Sanchez-Mejıas, Avencia Toscano, Carlos

Abstract: Gene therapy is a trending field that allows the treatment of diseases by insertion or modification genes inhuman cells. Despite the amount of genetic tools that biology has to offer, novel protein design is required speciallyfor fine tuned tasks such as in vivo gene editing. Directed evolution is a commonly used technique to generatenew and enhanced variants of genetic tools by exploring different variants and selecting the best performing ones.However, experiments are typically carried out in systems that do not match the mammalian environment limiting thescope of the target to be evolved. The retroviral synthetic evolution presented here, is a platform that uses lentiviraldelivery vectors as a way to perform directed evolution cycles in vivo. In this thesis, we will explore how to adapt theplatform to evolve two potential therapeutic tools: genetic activators and programmable transposase.

Different sets of genetic activatos and reporters were tested to find the best way of selecting the best variantsby fitness. This allows closing the evolutionary loop proving the cycling and automatization for the protein evolution.On the programmable transposase, two diversity generation methods were tested and characterised. First, mutage-nesis drugs were used to generate non-targeted variability among the whole protein. Secondly, a novel applicationfrom an existing Cas13-Deaminase base editing system in order to generate targeted mutagenesis in precisely selectedregions of the protein. Both techniques reported optimal mutation rates to be used in the platform. Moreover, theCas13-deaminase system showed tunable and multiplexable directed mutagenesis in the different targeted regions.

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These results suggest that the retroviral synthetic evolution platform is suitable to improve genetic tools to becometherapeutic.

Keywords: Synthetic Biology, Gene Therapy, Directed Evolution, Retroviral vectors, Focused mutagenesis

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Elisabet Sorribes Torrent

A novel approach to assess Alzheimer’s disease by using radiomics in TgF3p-44-Ad rats

Supervisor(s) UPF Tutor Referee 1 Referee 2

Munoz, Emma Piella, Gemma Pariente, Jose Carlos Soria, Guadalupe

Abstract: Alzheimer’s disease (AD) is a complex neurodegenerative disease that leads to progressive cognitive de-cline and memory loss. Nowadays, it is still very challenging to diagnose Alzheimer’s disease due to the complexity ofthe disease, the inter-individual differences and the late symptoms appearance. However, the use of animal modelscan contribute to improve early AD diagnosis in patients. Concretely, the combination of radiomics and MRI imagesof TgF344-AD rats could have a great potential in detecting quantitative imaging biomarkers of AD.

The main objectives of this project is to evaluate the ability of radiomics to discriminate between control (CTR)and transgenic animals (Tg) and also to evaluate the disease progression considering the cohorts young-CTR, old-CTR, young-Tg, old-Tg in three different regions, which are hippocampus, amygdala and thalamus.To accomplish this goal, radiomics and machine learning pipelines are developed in a Python implementation. Thedatabase is composed by 34 wildtype rats and 30 TgF344-AD animals, each of them evaluated at different agesbetween 3 and 18 months, resulting in 98 control images and 96 in Tg. Radiomics is applied to this database in orderto obtain the corresponding texture, shape and intensity features. Then, several machine learning algorithms are usedto test the biomarker combination obtained from the feature selection with the aim of finding the best model thatoptimizes the accuracy of the classification, and therefore, to obtain highly accurate non-invasive biomarkers of thedisease. In the binary classification of rat images between control and Tg animals, the highest accuracy reached inour method is 80.76% using hippocampus. Regarding the classification in the aforementioned 4 groups, an accuracyvalue of 82.69% is obtained in the hippocampus too.

Keywords: Alzheimer’s Disease (AD), Machine learning, Magnetic Resonance Imaging (MRI), Biomarkers,Radiomics features

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Ivan Dmitriy Ortiz Sanchez

Mode and tempo of cultural evolution in video games

Supervisor(s) Referee 1 Referee 2

Valverde, SergiDuran, Salvador

Vidiella, Blai Sardanyes, Josep

Abstract: The mechanisms of biological evolution also apply to artificial phenomena such as culture and technology,and the evolution of video games through history has been shaped by the evolution of technology itself. In particular,the so-called speedruns, which consist in completing video games in the least time possible, have become remarkablypopular recently. Since the evolution of performance in video games has never been quantitatively assessed, in thepresent study, we wonder whether there are universal patterns in the way speedrunning has evolved through videogame history. Specifically, we aim to identify relations between performance improvement and the size and structureof the player community. Thus, a reliable dataset with the results of official speedruns has been manipulated andanalysed. First, we describe the dynamics of performance improvement and growth of the community since itsorigin. Second, we explore the effects of community structure with a game-player bipartite network framework andan infectious model of strategy and information propagation. Finally, we relate the model to the actual data andestablish linkages between the properties of the network and the learning dynamics. Our results show how the growthof the community and the evolution of performance follow exponential descriptions and how the ranked distributionof players according to their number of playthroughs follows a power law-like behaviour. A first minimal networkmodel to describe the properties of the community is also provided. This study lays the foundation for a quantitativeapplication of biological and evolutionary models to the video game field.

Keywords: Computational modelling, Complex networks, Cultural evolution, Video games, Speedruns

Jaume Puig Costa-Jussa

Engineering Escherichia coli for Outer Space survival. Enhancing bacterial resistance to extremelevels of radiation, temperature, and pressure

Supervisor(s) Referee 1 Referee 2

Knodlseder, NastassiaGuell, Marc

Santos, Javier Gonzalez, Lourdes

Abstract: Some bacteria have shown the ability to naturally survive to extreme environments, even Outer Space.These bacteria have natural genetic mechanisms to protect and repair the DNA damage these severe conditions cancause, and this way can adapt and survive to these situations. A good example of this ability to survive can be foundin Deinococcus radiodurans, which is known for its high radiation resistance and has proven its ability to surviveunder severe conditions such as the exposure unit of the International Space Station. In this study, we translatedsome of these survival mechanisms to one of the most used experimental bacteria, Escherichia coli. Additionally, wealso tested a protein from tardigrades, which is involved in DNA damage repair. These mechanisms, which includeionizing and UV radiation, pressure, and temperature resistance, aim to provide a certain strain of E. coli with themechanisms it needs to survive to one of the most extreme environments, Space. This research constitutes a firststep in the creation of new strains and species engineered to survive severe conditions, opening the door to adaptingexisting species to survive on remote places and even other planets, such as Mars. Furthermore, this study shed somelight into the genetic mechanisms responsible for this survival, which could be beneficial for many scientific fields,such as medical sciences and life sciences engineering.

Keywords: Astrobiology, DNA Repair, Directed Molecular Evolution, UV Survival, Radiation Resistance

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Juan Manuel Dıaz Gimenez

Nanoparticle-assisted ROS production towards photothermal treatement of cancer

Supervisor(s) Referee 1 Referee 2

Rivera, Pilar Xiao, Can Guardia, Pablo

Abstract: Photo-dynamic therapy (PDT) refers to the use of special drugs, called photosensitizers-, along with lightfor the treatment of various pathological conditions including cancer. PDT is mostly used as an adjuvant therapyto other well-established therapies like chemotherapy or radiotherapy. Irradiation of the photosensitizer results inthe production of Reactive Oxygen Species (ROS) through Redox reactions with the environment. ROS play animportant role in cellular modulation. The presence of high levels of ROS can produce oxidative stress and eventuallyinduce a programmed cell death (apoptosis). Traditional PS have proven to be a technically feasible option but arelimited mainly due to three reasons: limited light penetration depth, low oxygen concentration in the hypoxic nucleus,and low PS accumulation within the tumor or the target tissue.Due to these limitations, its current use is restricted to very specific cases in which the technique is viable.Nanotechnology can provide solutions to this challenge.The main objective of this work is to use semiconductortitanium oxide nanoparticles (TiO2-NPs) as novel photosensitizer for PDT of tumours. TiO2-NPs are excellentphotocatalysts because of their unique optical and electronic properties. Within this work, we are going to validatethe ability of this NPs to produce ROS and cancer cell death upon light irradiation. TiO2-NPs are responsive toUV light however this is incompatible with living organisms, therefore for their use in biomedicine, their excitationrange must be shifted to NIR. To this end, we add a plasmonic (gold, Au) nanostructure to the TiO2-NPs i.e.,TiO2@Au-NPs. The Au nanostructure absorbs the light in the NIR and transfer the energy to the semiconductornanostructure, thus triggering ROS production. We have optimized the NIR laser irradiation system and have studiedthe relationship between power density and ROS production. For the final characterisation of the experimentalframework, an optimized irradiation system has been developed based on the study of the irradiation conditions in amathematical way. The analysis of the results has also been carried out by means of the computational modelling ofthis system. With the data obtained we performed a quantitative numerical approximation of the ROS productionmediated by TiO2@Au-NPs under the irradiation conditions tested. We conclude that TiO2@Au-NPs induce ROS-mediated tumor cell death upon NIR light irradiation and thus have the potential to be a viable and safe alternativeto standard strategies using organic compounds in PDT of cancer.

Keywords: ROS Production, Photo-Dynamic Therapy, Oxidation , RhB Bleaching, Laser Irradiation, PowerDensity, Photosensitizers

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Judith Martınez Gonzalez

Gene expression remotely controlled by an electronic device using a thermal interface

Supervisor(s) Referee 1 Referee 2

Macia, JavierGonzalez, Marc

Puig, Marta Guell, Marc

Abstract: Synthetic biology is a field of Biology that involves redesigning organisms for useful purposes by rationallyengineering them to have new abilities. The potential to re-engineer living organisms has provided tools to addressenergy, environmental or medical issues.One of the most promising applications of synthetic biology is the creation of bio-computational devices, which canbe used as biosensors for example. Recent advances in this field have been able to print 2D circuits in paper.The aim of this work is to improve this technology by building a new way of communication between these printedbiocircuits and electronic devices such as a computer or a phone. This will allow the control of biological computa-tional devices remotely. In this work we use temperature as the communication channel between the electronic deviceand the biological systems. In this approach the heat is provided by an Arduino-controlled resistor and sensed byengineered cells expressing an RNA thermometer sequence. To test our prototype, a generic GFP reporter system wasbuilt, consisting of a constitutive promoter and an RNA thermometer. The GFP expression of this reporter systemwas characterized as a function of temperature both in liquid LB culture and in printed paper placed on LB-Agar plates.

Increasing the complexity of the system, the use of recombinases such as Bxb1 allows in vivo DNA modificationswith the purpose to reprogram cells in a temperature-dependent manner. Designing the proper genetic architecture,we are able to change the cell type by performing flip or excision on their sequences.

This novel technology gives new opportunities for the creation of new remotely reprogrammable biosensors, whichcould be used to reach hostile environments such as the depths of the ocean or another planet.

Keywords: Biosensors, RNA thermometer, GFP, Bxb1Recombinases, Bluetooth

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June Monge Lorenzo

Population dynamics of tumor-tumor interactions underlying surgically triggered relapse

Supervisor(s) Referee 1 Referee 2

Sole, RicardAguade, Guim

Bartumeus, Frederic Vidiella, Blai

Abstract: Surgical removal of primary tumors is sometimes followed by an accelerated growth of previously dormantmetastases, significantly reducing survival rates in advanced cancer patients. This paradoxical observation suggestsa system-level interaction where the tumor is able to maintain metastatic growth under control by driving distantfoci into a quiescent state. The fact that surgical excision might disrupt this metastatic homeostasis questions theadequateness of this practice in specific tumor stages. The process underlying these growth-inhibitory dynamics,known as Concomitant Resistance (CR), is associated to a systemic diffusion of tyrosine-isomers that induce distantproliferative arrest. However, a coherent description of the population-level effects of CR is lacking. In the presentwork we aim at obtaining a minimal mathematical model capable of describing the ecology of tumor-tumor interactionsunder CR. In order to do so, 1) the capacity of adapted previous models to correctly capture CR-like interactionsand 2) the possible non-trivial interplay between growth inhibitors and recently characterized counteracting-agentsare analyzed. The model indicates that a local counteracting agent is key in explaining the observed dynamics ofCR. Furthermore, by comparing analytical approaches and in silico spatial simulations with previous experimentalobservations, the model establishes a systemic approach to understand the conditions governing tumor control anderadication. This provides a quantitative framework for the development of combined therapeutics that take advantageof growth-inhibitory agents with the aim of preserving metastatic-dormancy after primary-tumor excision.

Keywords: Cancer metastases, Surgery induced relapse, Concomitant tumor resistance, Tumor-tumor interactions,Ecological model

Justo Montoya Galvez

Seizure prediction and epileptogenic zone definition through pre-ictal state analysis

Supervisor(s) Referee 1 Referee 2

Prıncipe, Alessandro Zucca, Ricardo Maubens, Linus

Abstract: Around 0.3% of the whole world population is affected by drug-resistant epilepsy, a neurological chronicdisease that not only triggers epileptic seizures but significantly diminishes the quality of life of those who suffer fromit. Resection of the epileptogenic areas of the patient’s brain is one of the solutions to this situation. The difficultyof an entirely accurate topological determination of the epileptogenic region, the considerable resources required forthis function, together with the impossibility to perform surgery in some particular cases make the task a challengefor healthcare throughout the world. Relying on the new method for EEG state analysis developed by Dr AlessandroPrincipe et al, Prediction Error Connectivity, this thesis proposes an epileptic seizure prediction and epileptogeniczone prediction model, focused on a prospective online operation. The prediction is based on the task of classifyingthe interictal period, calculating the probability of a seizure occurring in the following instants.

Keywords: Epilepsy, Connectivity, Seizure Prediction, Epileptogenic zone

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Laura Orrit Vinets

Modelling immunogenicity in heterogeneous cancer cells under the immune system action

Supervisor(s) Referee 1 Referee 2

Sardanyes, Josep Vidiella, Blai Garcıa Ojalvo, Jordi

Abstract: Tumor cells heterogeneity is one of the most important handicaps in fighting cancer. Such heterogeneityis mainly driven by genomic instability, epigenetics and different sources of stochasticity. Heterogeneity providescancer cells with ways to escape to the action of the immune system or anticancer therapies. An important, and notyet completely understood process, is the dynamics between cancer cells and immune system cells (such as AntigenPresenting Cells (APCs) and both regulatory and effector T cells) for heterogeneous cancer cells with evolvingimmunogenicity. In this project thesis a computational model is developed explicitly considering heterogeneity oftumor cell populations with the capacity to evolve immunogenicity, affecting the recognition by APCs and thus thesubsequent action of both effector and regulatory T cells. A stochastic, agent-based model is developed implementingheterogeneity and differential, evolutionary immunogenicity by means of bit-strings simulations.

Keywords: Cancer, Complex systems, Computational Biology, Immune system, Immunogenicity, Stochasticsimulations

Laura Palacios Peral

Hip joint space analysis for osteoarthritis diagnosis

Supervisor(s) UPF Tutor Referee 1 Referee 2

Humbert, LudovicWinzenrieth, Renaud

Gonzalez, Miguel Angel Lopez, Mirella Ceresa, Mario

Abstract: The hip joint is one of the body’s largest weight-bearing joints and is commonly affected by osteoarthritis(OA). With hip osteoarthritis the cartilage within the joint begins to break down and the underlying bone beginsto change. The major pathological features for hip OA include joint space narrowing, osteophytes formation, andsclerosis.

The current gold standard for diagnosing OA is plain radiography, however, is insensitive when detecting earlyOA changes and it depends on the subjectivity of the practitioner. The development of machine learning algorithmswhich help in the study and diagnosis of many medical concerns has made huge progress.

In this paper a computer-aided method to facilitate OA diagnosis is proposed. Two different datasets were pro-vided and two different methods were developed for each of them. For the first data set, Unet Convolutional NeuralNetwork was applied to automatically segment the hip joint space. Moreover a quantitative analysis of the jointspace width (JSW) was performed to study the relationship between joint space width and antropo morphometricparameters. On the second dataset, with known conditions of osteoarthritis, images were classified with VGG16neural network.

Results of the automatic segmentation had a Dice Coefficient of 0.835. Inverse relationships between joint spacenarrowing and age were found and differences between men and women were significant. Regarding the seconddataset, images were classified with a precision of 0.98 and a recall of 0.98. While the approach is a step in thedirection of OA diagnosis, developing a tool that is accurate enough to be applicable in a clinical context still remainsan open challenge.

Keywords: Osteoarthritis, Machine learning, Convolutional Neural Networks, Detection method, Joint space width

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Laura Perez Sanchez

Automatic detection of new lesions in patients with multiple sclerosis using the T1-w/T2-wmagnetic resonance ratio

Supervisor(s) UPF Tutor Referee 1 Referee 2

Pareto, Deborah

Camara, OscarPiella, Gemma Gonzalez, Miguel Angel Cabezas, Mariano

Abstract: Multiple sclerosis is an autoimmune condition in which the immune system mistakenly attacks the myelinsheath, meaning that messages travelling along the nerves become slowed or disrupted. Currently, the severity ofthe disease progression is given by the appearance of new lesions. The aim of the project is to demonstrate that byusing T1-w/T2-w magnetic resonance ratio, additional lesions can be measured, when compared to Fluid-attenuatedinversion recovery (FLAIR) images. For this purpose, follow-up and baseline images are used in order to obtainsubtraction images. Then, the subtraction images are redefined using deformation field and local tissue informationto detect disease activity. In this study, a database of 100 patients is employed, of which 34 present new lesions. Theevaluation consists of comparing the results with the ground truth of new lesions already established from FLAIRimages and calculating metrics for detection. The method shows sensitivity to inconsistencies in the registration andintensity differences. Therefore, it is necessary to carry out a post-processing of the results in order to eliminate mostof the detections that do not correspond to new lesions, leading to an increased difficulty when locating the smallestones. Still, new lesions are detected employing this method that were not considered in the ground truth. This isimportant in cases in which the patients presented new lesions in the follow-up and went unnoticed. Thereby, thisapproach could be used in a real clinical environment to help on the detection of new lesions.

Keywords: Brain MRI, Multiple sclerosis, T1-w/T2-w, White matter lesions, Deformation field

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Mar Martınez Mas

Study of the hydroelectrolitic mass transfer of calcium in haemodialysis patients and its correlationto intradialytic hypotension and parathormone unbalances

Supervisor(s) UPF Tutor Referee 1 Referee 2

Costantino, Marıa LauraCasagrande, Giustina

Ivorra, Toni Garcıa-Ojalvo, Jordi Possenti, Luca

Abstract: During haemodialysis, the composition of the dialysis fluid is typically prescribed by a nephrologist. Nev-ertheless, calcium and parathormone imbalances and the symptomatic hypotension that the patients suffer whileundergoing haemodialysis therapy, imply the need of changes in the calcium concentration of the dialysate, to im-prove its tolerance to HD.

In this thesis it is proposed a model that allows us to know the balance of calcium together with the dialysissession, given a certain value of the initial calcium concentration and the patient characteristics. To this end, amodel able to simulate and predict the patient’s specific response to HD treatment, taking into account the clinicalconditions of the individual patient, has been designed and optimized. Calcium exchange is specifically modelled atdialyzer, vascular, extracellular, intracellular and bone level.

An analytical multi-pool model can be used to represent the body compartments and the dialyzer. Specific modelsdescribing only the calcium exchange during dialysis were available in the literature. Calcium peculiarities have beenstudied integrated into a multi-solute model already available at LaBS, DCMC, PoliMI.

The results show that a a more accurate description of calcium metabolism in the model improves its predictionthrough simulations. An average prediction error of 1.83% was obtained with a maximum error obtained of 11%.Based on the simulation results and the analysis of patient-specific parameters, the proposed approach enables theextraction of conclusions regarding the relationships that exist between hypo and hyper calcemia generated in dialysistherapies and PTH unbalance and intradialytic hypotension cases. This way, dialysis planning would be facilitatedand therapy complications reduced.

Keywords: Haemodialysis, Parathormone Disorders, Hypotension, Dialysis Solution Concentration, CalciumExchange Modelling

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Marc Amilibia Sison

Study of preoperatory field placement deformation to assess oropharynx surgery

Supervisor(s) UPF Tutor Referee 1 Referee 2

Saez, Pablo Noailly, Jerome Ruiz, Carlos Mill, Jordi

Abstract: When performing surgical treatment in benign and malignant lesions in the oropharynx, transoral roboticsurgery (TORS) is the most viable approach. In order for the robot to be introduced through the mouth, a mouthretractor is used, opening the mouth and flattening the tongue, causing anatomical changes in the oropharyngealarea. Although using TORS has plenty of advantages, surgeons have to rely on preoperative images without thedeformation to plan the surgery, leading to many complications. This thesis aims to study such deformations bycarrying out a mechanical simulation. To accomplish that, 3-Tesla full-head MRIs of a voluntary were taken inbaseline position and with a non-metallic mouth retractor. Segmentations of the tongue, mandible, pharynx, carotidsand other anatomical landmarks were performed and transformed into 3D surface meshes. Later, the developmentof volumetric meshes of the structures was performed using Salome Meca. Finally, a mechanical deformation of themodel during the retractor’s introduction into the mouth was described using a finite element analysis through Abaqussoftware. This simulation is the basis for designing a tissue deformation prediction platform to assess surgeons, whichwill allow an improvement in the performance of TORS in the pharynx.

Keywords: Oropharynx cancer, Transoral robotic surgery, Soft tissue mechanics, Finite Element Method,Mechanical simulation

Marcos Chic Cobreces

Development of an open-source, wireless and implantable vagus nerve stimulator for preclinicalstudies in mice

Supervisor(s) Referee 1 Referee 2

Ivorra, ToniBecerra, Laura

Comerma, Albert Ceresa, Mario

Abstract: Vagus nerve stimulation is expected to be a promising neuromodulation therapy capable of treating awide variety of diseases like obesity, atherosclerosis, type II diabetes or heart failure; moreover it has already beenapproved for depression and epilepsy. The advantages of neuromodulation-based treatments over pharmacologicaland surgical approaches are clear since they mean a non destructive and reversible alternative. Moreover, they canavoid the large ingest of drugs that many treatments entail nowadays, avoiding therefore their side effects. Vagusnerve (tenth cranial) constitutes an interesting target for this type of stimulation since it is well known that it playsa major role in inflammatory pathways and the amount of diseases related with inflammations is huge. Taking all ofthis into consideration, it can be understood the increasing need of functional long-lasting vagus nerve stimulatorsfor pre-clinical research in rodent models. In addition, the current lack of this type of commercial stimulators (noneof them open-source) in the market makes this work more essential. The proposed device is aimed to be open-sourceand fully implantable and wireless, avoiding thus percutaneous wiring that makes the device less hardwearing. Toaccomplish this, the stimulator will be battery-powered. Besides, it will probably be current controlled and usebiphasic pulses for the stimulation. However, its development will have to cope with several issues such as its powerconsumption (crucial for the dimensions), miniaturization, remote control, delivery of adjustable and exact currentpulses or a proper encapsulation (to prevent infections and ensure durability).

Keywords: Neurostimulation, Vagus nerve, Mice, Implantable, Wireless

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Marıa Ballart Vernet

Influence of bone in the biomechanical response of knee cartilage in gait cycle of patients withosteoarthritis: A finite element study

Supervisor(s) Referee 1 Referee 2

Ruiz, Carlos Tassani, Simone Ramırez, Juan Fernando

Abstract: Osteoarthritis of the knee is a very prevalent, progressive disease which affects a lot of people nowadays.Its symptoms include pain and swelling of the joint, which can be treated by conservative treatments, like anti-inflammatories or physical therapy, or non-conservative, more invasive techniques like knee arthroplasty. To study thepathology, numerical and in-silico models are used. Currently, most of the 3D Finite Element models available in theliterature consider the bones to be rigid bodies. This fact results in a null load absorption by the bone, transmittingthe full load to the cartilage. In the actual joint, bones act as load absorbers, decreasing the load applied to thearticular cartilage. This difference, although resulting in small errors of 2-3%, can suppose a big change in cellbehaviour. Hence, the aim of this study is to implement bone structures in the current knee joint model and evaluatethe influence of bone properties on knee cartilage biomechanical response on healthy patients.

Keywords: Osteoarthritis, Articular cartilage, Finite element models, Knee joint

Maria Pol Cros

Cutibacterium acnes extracellular vesicles: characterization and modulation of the skin immuneresponse

Supervisor(s) Referee 1 Referee 2

Fabrega, Marıa Jose Santos, Javier Pallares, Maria

Abstract: The human microbiome plays an essential role in maintaining the host health. One of the most commonbacteria present in the skin microbiota is Cutibacterium acnes (C.acnes) which is known for being involved in thehomeostasis of the skin, but in some other cases, it can act as an opportunistic pathogen contributing to some skinalterations like acne vulgaris. Recently, some authors have claimed that different strains of C.acnes have differentdegrees of association with acne vulgaris. For instance, it has been shown that C.acnes subtype H1 was presentin patients who had never developed acne vulgaris before. Therefore, a protective role has been hypothesized forthis phylotype. In addition, C.acnes extracellular vesicles (EVs) have been reported to play an important role inthe inflammatory profile of skin cells. Nevertheless, their protein, lipid and nucleic acid content have not been fullycharacterized yet. In the present project, EVs have been isolated from different C.acnes strains (A1, H1 and KPA)and their cytotoxicity has been tested with an immortalized keratinocyte cell line (HaCaT) and an immortalizedsebocytes cell line (SZ95). In parallel, the immuno-modulation role of these EVs has been studied using a 2D skininflammatory model, which mimics the in vivo skin layers considering both the epithelial and the immune system.On the other hand, it is important to know the content of the EVs to determine if they could have a probioticbehavior themselves or, otherwise, be an appropriate drug delivery vehicle. RNA sequencing and a proteomic analysisare going to be conducted in order to elucidate it.

Keywords: Microbiome, Extracellular vesicles (EV), Cutibacterium acnes, Skin inflammation, Acne vulgaris

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Marian Iglesias Blanco

In-silico modelling of the deployment of left atrial appendage occluder devices. A sensitivityanalysis

Supervisor(s) Referee 1 Referee 2

Casoni, EvaMill, Jordi

Olivares, Andy Santiago, Alfonso

Abstract: Percutaneous left atrial appendage (LAA) occlusion interventions are an alternative to oral anticoagulantsfor cardioembolic stroke prevention in atrial fibrillation patients. Preoperative insights into how the occluder devicewill interact with the patient’s LAA anatomy are limited. Choosing the optimal device type, size and position remainschallenging, leading to procedural complications such as device embolization, device-related thrombosis and leaks.Computational tools could provide a personalised pre-operative planning to minimise possible deployment problems.

The present study aims at finding the prinicpal steps for the in-silico deployment of LAA occluders in patient-specific anatomies. The most relevant factors in finite element modelling (FEM) to ensure a realistic interactionbetween the device and the anatomy were studied, including mesh discretization, material properties and boundaryconditions.

A sensitivity analysis study was designed and executed on a geometrical model built based on Computed Tomographyimages of a patient who underwent a LAA occlusion at Hospital de la Santa Creu i Sant Pau (Barcelona, Spain).Due to the high computational burden associated to the computational solid mechanics simulations required in thisproject, the study was performed using codes optimised for High-Performance Computing (HPC) infrastructures,including the Alya FEM solver developed by the Barcelona Supercomputing Center, which also gave access to HPCfacilities to run the experiments.

The current project has led to some relevant conclusions regarding the geometry characteristics, methodology andmaterial selection to model LAA occluder deployment. It has set up the basis for future developments where arealistic device deployment could be offered as an option to clinicians for a better pre-procedural planning.

Keywords: Computational Solid Mechanics, Left Atrial Appendage Occlusion, High-Performance Computing,Pre-operative planning, In silico Device deployment

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Marina Xicoira Serra

Assesment of 4D aortic strain from 3D time-resolved MRI in aortic aneurysms

Supervisor(s) UPF Tutor Referee 1 Referee 2

Guala, Andrea Camara, Oscar Dux, Lydia Piella, Gemma

Abstract: Aortic aneurysms are a class of frequent cardiovascular disease related to an increased risk of life-threatingcomplications, such as aortic dissection and rupture. These acute events are characterized by a very bad prognosis,with mortality comprised between 60 to 70%. Maximum aortic diameter is the sole established parameter for riskassessment but many acute events happen at a diameter lower than that suggested for preventive substitution of thediseased region. Aortic deformation may allow for better risk stratification. Three-dimensional (3D) time-resolvedcine magnetic resonance images (CMR) allows the quantification of strain over the totality of the aorta, overcomingmany limitations of 2D imaging, such as the predefined location of analysis and through plane deformation. Theaim of the present study is to assess 4D strain of the whole thoraco-abdominal aorta during one cardiac cycle. Thedataset is provided by Hospital Universitari Vall d’Hebron and consists on 3D cine CMR and contrast-enhanced3D angiography (MRA). 3D volume of the whole thoraco-abdominal aorta is obtained from contrast-enhanced 3Dangiography and allows to identify the aortic wall and extract deformation values at those points. Volumetric imagesof the aorta from 3D cine CMR at different cardiac phases are registered and the deformation field at the aorticwall is extracted and analysed. Local strain of the wall is divided in regions allowing the comparison of longitudinal,circumferential and radial strain among the cohort. The evaluation of aortic strain may help to monitor and evaluaterisk in patients with aortic aneurysms.

Keywords: Magnetic resonance imaging, Aneurysm, Aortic dilation, Aortic strain

Marta Benavides Lasala

Business plan for the creation of a capacity and occupancy tracking smartphone app: EasyCount

Supervisor(s) Referee 1 Referee 2

Bosch, Jordi Manzanera, Rafael Domingo, Susana

Abstract: This project is the product of my interest in the world of technologies (in this case, mobile technologies)and its application in the healthcare world, a mixture of which my degree, Biomedical Engineering, is composed.Also, it will be intimately related with the e-Health –which, according to WHO (World Health Organization), is ”thecost-effective and safe use of information and communication technologies in support of health-related fields” – and,more precisely, with m-Health – ”the practice of medicine and public health supported by mobile devices such astelephones, patient monitoring devices, digital assistants and other wireless devices”.

On the other hand, the motivation to choose the type of application to design was the current context that, un-fortunately, we all know: the global Covid-19 pandemic that the entire world is living. It is for this reason that Iselected the development of the business plan of an application to know the number of people there are in a certainpublic place –like a restaurant, a classroom, a workplace, a plant of a hospital, etc. Therefore, the intention is toanalyse this proposal from a business point of view in order to determine if it is a good business and if it is worthinvesting in it, that is, if there is a market and people willing to pay for this service. In addition, the best technologyto implement it will also be studied.

Keywords: M-health, Mobile applications, Covid-19, Data storage and management, Business Plan

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Martın Esparza Iaizzo

SleepBCI: a platform for sleep quality assessment and memory enhancement based on automaticscoring

Supervisor(s) UPF Tutor Referee 1 Referee 2

Lopez-Larraz, Eduardo Garcıa-Ojalvo, Jordi Soto-Faraco, Salvador Bibian, Carlos

Abstract: Sleep is a complex physiological process responsible for several developmental, restorative and cognitiveprocesses. Sleep related disorders diminish life quality, and their diagnosis relies on classifying 8-hour polysomno-graphic (PSG) recordings. Manual scoring is the gold standard for analyzing sleep and is a time consuming task thatcan only be performed by trained experts. We propose SleepBCI, a platform that integrates sleep quality analysis andclosed-loop memory enhancement using automatic sleep scoring as its cornerstone. Firstly, real-time sleep stagingis carried out through a convolutional deep neural network capable of achieving accuracies of 80-84% on a variablenumber of channels (1 to 6). Employing the neural networks output, we create an automated sleep quality reportwith objective metrics. This way, we characterized significant differences between healthy individuals and patientssuffering from diverse sleep disorders, such as breathing disorders, insomnia and narcolepsy. Furthermore, we imple-mented a brain-computer interface based on monitoring EEG activity in real time, intended to enhance previouslylearned memories during deep sleep. We validated it in a controlled study on healthy participants, who performed aword-sound association task before and after sleep. Recall performance values after waking were significantly greaterin reactivated cues compared with non-reactivate cues. The platform and results presented in this work serve as aproof-of-concept for future sleep technology. It lays the foundation for a telemedicine device capable of alleviatingthe workload of physicians, preventing at-risk populations (elderly or obese patients) from unnecessary PSG tests andfinally, delivering therapy to slow cognitive impairment or dementia.

Keywords: Sleep, EEG, Deep Learning, Brain-Computer Interface, Memory enhancement

Martina De la Varga Rodrıguez

NanoLuxe: a market analysis, pricing policy and regulatory affairs for an anti-counterfeit companybased on nanotechnology

Supervisor(s) Referee 1 Referee 2

Rivera, Pilar Mir, Bernat Brunet, Nuria

Abstract: Counterfeit is an ever-present phenomenon that involves making illegal copies of valuable items with theintention of making profit from their transactions. The vulnerabilities in the supply chain of medical devices have setthe ground for these criminal groups to target the medical industry. Substandard and unauthorized medical productsare currently in the market, putting millions of people at risk and being a serious threat to public health. NanoLuxe isa company that is developing a system to label and identify products with barcoded-nanoparticles, guaranteeing thetraceability and authentication of goods down the supply chain. A market analysis is performed in order to evaluatewhether this business could be profitable in the medical devices industry. With the information gathered in themarket analysis and the definition of a clear market niche, a pricing policy and strategy is carried out. Accordingly,this is accomplished by analyzing the level of competition, the supply and demand curves, the scalability of the sectorand the cost-effectiveness of the technology. Furthermore, the regulatory affairs that this technology requires at anEuropean level and under the FDA (Foods & Drugs Administration) regulations are assessed.

Keywords: Anti-counterfeit, Medical devices, Market analysis, Pricing policy, Regulatory affairs

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Mayra Alejandra Loayza Saldana

Scaling of a full three-dimensional knee joint model for the study of osteoarthritis: towardsdeveloping a patient-specific model

Supervisor(s) Referee 1 Referee 2

Ruiz, Carlos Tassani, Simone Ceresa, Mario

Abstract: Articular cartilage degeneration is consequence of knee osteoarthritis (OA). There is not a clear aetiologyor understanding of OA’s natural course since it is a multifactorial condition. Finite Element models can be usedto simulate knee joint mechanics and prevent injuries, being the geometry an essential part. The more accurate thegeometry is the better will represent the tissues of the joint. However, most studies utilize a generic model of theknee which can lead to an over/under estimation of the effects of stimuli at the cartilages. Thus, the purpose ofthis study is to scale a 3D mesh of a knee joint to match the knee’s dimensions of actual patients with OA, as afirst step to obtain a patient-specific model. For that, a segmented knee of a patient and the generic mesh of a kneemodel are used. The scaling is performed by implementing the homothetic function to the nodes of the mesh. Then,gait simulation using real data of the force and time is conducted, by fixating the bottom of the tibia and applyingthe load on the rotation point of the knee model. Contact pressure (CP) and water content are evaluated. Resultsshow a decrease in CP of 5.64% in the scaled model compared to the standard model. Zones with a high CP presentlow water and proteoglycans content indicating a critical point of tissue degradation. Besides, the scaling methodmanages to adapt the dimensions of the model to the anatomy of a particular patient. These results suggest geometrymust be considered to better interpret the simulation’s outcomes. Next step would be carrying out a morphing toobtain an actual representation of the knee geometry. With personalised data from simulations, clinicians can improvethe diagnostic and develop more specific treatments for the patient.

Keywords: 3D finite element model, Knee osteoarthritis, Patient-specific, Dimensional scaling, Homothetictransformation

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Miriam Caravaca Rodrıguez

Continuous Vibrio cholerae detection and quantification through a biosensor with geneticallyengineered Escherichia coli

Supervisor(s) Referee 1 Referee 2

Mogas, SiraMacia, Javier

Gallego, Oriol Knoedlseder, Nastassia

Abstract: Vibrio cholerae is the causative agent of cholera, a potentially mortal infectious disease. Cholera is presentin many areas of the world and the treatment still has limitations. For that reason, the preventive detection of thisbacteria in potential environmental sources could be an interesting tool to avoid people getting infected. Althoughthere are several options in the market, current detection methods require DNA amplification techniques and high-cost machinery with qualified technicians, only being optimal once the person is infected. Our approach uses agenetically engineered non-pathogenic Escherichia coli which can detect specific peptides from the bacterial quorumsensing. In the literature, it is well-established that these molecules can be directly correlated with bacterial density.Thus, the genetic circuit has been designed to detect the presence of these peptides in the supernatant of a culture,characterizing the response by the expression of the green fluorescent protein (GFP) and blue chromoprotein AmilCPas the output signals. The aim of this project is to develop an easy-to-use device to detect V. cholerae in watersamples. During this work, different approaches have been tested, such as continuous GFP quantification, AmilCPcolour scale determination methods, as well as different strategies for long term storage of these living biosensors, i.e.lyophilization methods. A surveillance test has also been performed to determine the efficiency of storage methodswith respect to the fresh culture. This study could have a considerable impact providing cheap straightforwardpotential tools for the prevention of cholera in those regions where the disease is still endemic.

Keywords: Synthetic Biology, Biosensor, Cholera, Vibrio cholerae

Mitar Nikolic Jovanovic

Design and development of an active balancing stick for enhancement of mobility

Supervisor(s) Referee 1 Referee 2

Noailly, Jerome Ivorra, Toni Ceresa, Mario

Abstract: Mobility represents an essential aspect of daily life and favors the autonomy of older adults. The WorldHealth Organization (WHO) predicts an increase of 150% of people older than 65 years from 2010 to 2050. Nowadays,20% and 50% of people older than 70 and 85 years of age, respectively, suffer from movement limitation, whichrepresents a pre-clinical transitional stage in the pathway to disability. Those limitations have a big impact, sincethey affect to the functionality of physiological systems by increasing sedentarism and the risk of heart diseases, highblood pressure, stroke, and cholesterol among others. For that reason, is crucial to develop devices to assist elderlyin their daily life. However, traditional walking aids like sticks or canes and crutches that aim to provide posturalstability have poorly evolved over the last centuries. The lack of dynamic stability provided by the aforementionedaids is compensated by muscle strength, which often demotivates users and increasing sedentarism. This can only beaddressed through active systems. The project aims to provide proof of the scientific concept that the design of theinvention ”Gait-assisting Stick”, submitted in the form of a patent application to the European Patent Agency, byGLOBAL PALDOR S.L, is effective enough to achieve the objective of lifting a stick towards a vertical orientationwhen it is undesirably tilted with respect to the horizontal plane.

Keywords: Aging, Mobility limitations, Gait-assisting devices walking stick, Self-balancing cane

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Olalla Aramburu Cabada

Enhancing surgeon action detection in robot-assisted minimally invasive surgery

Supervisor(s) Referee 1 Referee 2

Jimenez-Sanchez, AmeliaPiella, Gemma

Tassani, Simone Pena, Oscar

Abstract: Although minimally invasive surgeries have achieved unbelievable results during the last decade, morecomplex surgeries require higher technology, such as robotics. The SARAS (Smart Autonomous Robotic AssistantSurgeon) Project has developed a novel challenge that seeks making minimally invasive surgery safer. For this, theyhave built a machine learning algorithm that is able to identify and localize the surgical actions performed by themain surgeon.

This study aims to improve the results from the baseline model provided by the SARAS Project, which is basedon the combination of a ResNet and a Feature Pyramid Network. Towards this end, an ablation study was performedthrough the implementation of different preprocessing techniques: removal of the black borders that surround theimages, data augmentation of specific surgical actions that are poorly represented over the others, and hyperparame-ter optimization regarding the loss function, the input size of the images and the number of iterations. Also, a noveldeep learning framework for real-time spatiotemporal action localization and classification was implemented in orderto explore temporal connections among the detected actions and evaluate their impact on the results of the formermodel.

Keywords: SARAS-ESAD, Deep learning, R-MIS, Action-Detection, Feature Pyramid Network (FPN)

Paula Casademunt Porte

Development of a patient-specific pipeline for the modelling of mitral valve interventions withmeshless techniques

Supervisor(s) UPF Tutor Referee 1 Referee 2

Morales, HernanBijnens, Bart

Mill, Jordi Soudah, Eduardo This, Alexandre

Abstract: Computational modelling is becoming a crucial aid to better understand valve physiopathology. This toolallows experts to gain deeper insights on the valve biomechanics and deformation, and hence, help in the planningof therapies, assessing efficacy of cardiovascular devices. Mesh-based methods encounter some limitations whenmodelling cardiac valves, being structures with high deformations. Despite high levels of accuracy are achieved, themeshing step becomes an extremely laborious and time-consuming task, becoming a bottleneck in the modelling pro-cess. In this work, a novel pipeline for the modelling of mitral valve (MV) interventions is developed using SmoothedParticle Hydrodynamics (SPH), a meshless methodology. SPH is introduced as a tool to deform and personalize theMV geometry and model the three types of minimally invasive interventions for mitral valve regurgitation (MVR):edge-to-edge repair, annuloplasty and chordal replacement. Furthermore, a flattened view of the MV is introduced,allowing a straightforward visualization of the simulations’ outcomes. Obtained results show that the model presentedhas the potential to become a powerful tool in the clinical setting, due to its ability to predict therapeutical outcomesin a patient-specific way, improving the safety and efficacy of the devices.

Keywords: Mitral valve regurgitation, Smoothed Particle Hydrodynamics (SPH), Edge-to-edge, Annuloplasty,Chordal replacement

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Paula Domınguez Gomez

Sensitivity analysis of haemodynamic modelling in coronaries

Supervisor(s) UPF Tutor Referee 1 Referee 2

Aguado-Sierra, JazmınButakoff, Constantine

Camara, OScar Olivares, Andy Soudah, Eduardo

Abstract: Recent advances in medical imaging, computational power and mathematical algorithms have led to theemergence of patient-specific computational fluid dynamics (CFD). This has paved the way towards computer-aidedcardiac diagnostics and therapeutics design. However, CFD models usually are complex and expensive in compu-tational and time terms, what does not satisfy clinicians’ requirements of accuracy and rapidity. In the case ofcoronary artery disease (CAD), the lack of consensus in how to create a faithful model supports the assessment ofemerging applications based on haemodynamic indices and plaque characterization in order to provide personalizedrisk assessment, disease detection, and further guided therapy.

The objective of this work was to study the blood flow of patients with coronary artery disease by assessing dif-ferent boundary conditions and anatomies, with the purpose of finding the optimal environment for coronary bloodflow simulation. Special focus will be given to haemodynamic parameters, such as fractional flow reserve (FFR) andinstantaneous wave-free ratio (iFR). The ultimate conclusion to be extracted from this study is which are the physicaland geometrical conditions needed to set the basis towards a useful clinical CAD assessment tool.

Keywords: Coronary disease, Computational fluid dynamics (CFD), Blood flow, Haemodynamic indices.

Quim Martı Baena

The role of whole genome doubling in cancer evolution

Supervisor(s) Referee 1 Referee 2

Sole, RicardAguade, Guim

Bartumeus, Frederic Vidiella, Blai

Abstract: Whole genome doubling (WGD) is one of the most common events in the early stages of cancer evolution.However, a consistent explanation for the pervasiveness of WGD across cancer types remains elusive. The duplicationof the whole karyotype, produced by errors in cell division, is often followed by an increase in chromosomal instability(CIN) and intratumor heterogeneity, possibly allowing cancer cells to rapidly evolve and overcome selective barriers.This would explain why WGD has been associated with poor prognosis and multi-drug resistance along several cancertypes, but it is not sufficient to account for why WGD arises and is selected for even before the onset of CIN. Inthis work, a mathematical framework to model instability in the cancer genome is presented, inspired by early virusmutagenesis models. By considering the intertwined effects of ploidy and mutational rates in a simplified genome,the model is able to capture how the average chromosome number correlates with potential evolvability. This, inturn, might point towards WGD providing a buffering effect to cancer cells that could allow the presence of theincreased genome instability that is produced by CIN. In addition, our model indicates that experimentally observedploidy values might not be the result of the negative effect of high ploidy on tumor suppressor gene inactivation, apreviously unresolved hypothesis.

Keywords: Reliability theory, Cancer evolution, Genome instability, Cancer aneuploidy, Whole genome doubling

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Roi Carrera Boo

Automatic detection and analysis of visual patterns and movement of lampreys for neurologicalinvestigation

Supervisor(s) UPF Tutor Referee 1 Referee 2

Perez, Juan Garcıa-Ojalvo, Jordi de la Torre, Roberto Haro, Gloria

Abstract: Visual stabilization is a crucial feature that allows multiple advanced visual behaviors by clamping the visualscene, and it is performed via optokinetic and vestibular reflexes. The vestibulo-ocular reflex is well neurologicallydescribed and known to be mostly shared between vertebrates, but its evolutionary origins and how it interacts withvision are less known. The study of this integration and mechanisms is performed using lampreys, belonging to theoldest vertebrates alive, due to their more simplistic nervous system and experimental accessibility. An ongoing studyshows that they exhibit robust visuo-vestibular integration. In order to obtain deeper knowledge, it is necessary toknow if they exhibit saccades in the form of nystagmus, as this would show that the basic components of all eyemovements were already present at the dawn of vertebrate evolution, indicating that the underlying basic neuronalpathways are conserved. For this, videos with different experimental preparations are recorded and then analyzed, notonly for nystagmus, but also for every eye movement. This requires a precise analysis that, if performed manually,is very tedious and time consuming, and can lead to many errors due to the required precision of measure for eachframe of the lamprey videos. In order to overcome this issue, a machine learning approach is taken. DeepLabCutis a software for deep learning using python that specializes in animal pose tracking and estimation. Trainings withdifferent neural nets and parameters were tried to find the combination that best fitted the necessities of the group,regarding accuracy and efficiency. In addition, some python scripts were created to ease the training process forpeople less familiarized with the software.

Keywords: Gaze stabilization, Machine Learning, Nystagmus, Lamprey, DeepLabCut

Sandra Gonzalez Alonso

Occipital alpha oscillations and sex differences

Supervisor(s) Referee 1 Referee 2

Torralba, MireiaSoto, Salvador

Drew, AliceRuzzoli, Manuela Lopez, Ane

Abstract: Ever since the first observations, it is known that the human electroencephalogram during relaxed wake-fulness is dominated by neural activity in the alpha frequency ( 10Hz). The frequency peak of alpha varies betweenindividuals but is fairly consistent within each person and highly heritable. This is known as the Individual AlphaFrequency (IAF). The IAF is related to a wide variety of cognitive processes and neuropathologies, being an impor-tant biomarker for diseases such as schizophrenia, Alzheimer’s disease or autism. Remarkably, the predisposition andincidence for some neuropathologies differ between male and female. However, when it comes to sex, there is stilla big gap in research in neuroscience. Nowadays, it is becoming clear that the possible difference in the expressionof neuropathologies across sexes can lead to the loss of relevant information for prevention, diagnosis and treatmentif sex is not considered. So far, few studies have focused on sex differences in alpha oscillations, and the results aremixed. Here we extract the peak alpha frequency of a large sample of male and female subjects (N¿400) gatheredfrom different datasets. It is analysed using a mixed model, taking into account the variability that may arise fromthe fact that the datasets were collected separately. This is done in order to look for possible significant differencesbetween sexes that could serve as a basis for further exploration. Although the IAF is a potential biomarker, there isno consensus on the method of extraction. This thesis applies a novel, automated method that takes into accountthe quality of the recording channels.

Keywords: EEG, Alpha waves, Oscillations, Individual Alpha Frequency (IAF), Sex differences

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Sergi Marcoval Martınez

Alteration in nerve function following electroporation: A numerical modeling study of theelectroporation conductance effect

Supervisor(s) Referee 1 Referee 2

Ivorra, ToniGarcıa-Sanchez, Tomas

Perera, Enric Mercadal, Borja

Abstract: It is known that after the application of external electric fields, aqueous pores are formed in the cellmembrane at the molecular level, non-selectively increasing its permeability, and therefore increasing the conductanceof the membrane to any ion. This process is called electroporation, and its effects may alter the cell’s ability todepolarize. This bachelor’s thesis aims to develop a mechanistic model in order to plausibly assess whether thereduction in conduction velocity and the blocking of the propagation of action potentials in nerve fibers, observedin some animal experiments, is due to primary effect of electroporation on the membrane. The cable model hasbeen used to evaluate the effect of electroporation conductance on nerve fibers. This conductance has been modeledfollowing two approaches at different level of detail: constant or voltage dependent. Finally, the results suggested thatthe electroporation conductance may alter the function of nerve fibers, being able to reduce its conduction velocity,block completely the action potential propagation along it, and reduce its excitability. In this way, this model couldpredict whether a nerve fiber would be desensitized, given a certain distribution of the applied external electric field.Therefore, it may be useful to develop new electroporation-based treatment methods, in which muscle contractionsand acute pain appear as a side-effect, leading to multiple clinical complications.

Keywords: Electroporation, Nerve stimulation, Nerve block, Membrane conductance, Electroporation conductance

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Sergi Navarro Guimera

Auricular transcutaneous vagus nerve stimulation device in the form of a pod: A first step towardschronic non-invasive vagus nerve stimulation in mice

Supervisor(s) Referee 1 Referee 2

Ozaita, AndresIvorra, Toni

Moreno, Ruben Vazquez, Anna

Abstract: Vagus Nerve Stimulation (VNS) has the potential to modulate the activity of subcortical and corticalcircuitry. Relatedly, chronic implantable vagus nerve stimulators, as well as acute and chronic auricular ones, haveshown to be effective at a clinical level in controlling refractory epilepsy, as a co-adjuvant in the treatment of majordepression, or in cognitive enhancement. However, research in rodent models so far has been limited to acute non-invasive stimulation, or to chronic invasive stimulation. While the underlying effects of acute stimulation are far fromthe physiological and molecular pathways activated in chronic stimulation, invasivity is accompanied with surgical andtechnical challenges with the microscopic anatomy of the mouse. There is a need for a simple, well-characterized,and reliable non-invasive chronic VNS technique. In the present study, after intense trial and error, we design,produce, and test a device in the form of a pod for auricular transcutaneous Vagus Nerve Stimulation (atVNS) inmice. This is also compatible with a proposed preliminary model of a chronic atVNS interface. atVNS has recentlyattracted great attention as the most affordable, non-invasive central nervous system manipulating technique. As amatter of fact, our group already proved the pro-cognitive effects of acute atVNS in naıve and intellectually disabledanesthetized CD1 mice. Such finding is intended to be corroborated in our investigation using the proposed pod.Additionally, the implementation of an innovative technique to test the stimulation sites, and the better adaptationof the pod in the concha of the mouse makes the results more reproducible. All in all, the present work supposesa first step to implementing non-invasive chronic VNS in mice. Further work could conceivably open new doors tounearthing the molecular, neurological, and anatomical mechanisms underlying the cognitive effect of chronic vagusnerve stimulation.

Keywords: Auricular transcutaneous vagus nerve stimulation, Cognitive enhancement, Stimulation sites,Elizabethan collar, Chronic atVNS

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Silvia Perez Garcıa

Pharmacological experiment on neurodegeneration in mature trisomic mouse models

Supervisor(s) Referee 1 Referee 2

Ozaita, Andres Picon, Pol Aso, Dr. Ester

Abstract: Down syndrome (DS) is the most common cause of intellectual disability and a genetic cause of earlyAlzheimer’s disease, produced by trisomy of whole or part of chromosome 21. Nevertheless, no gold-standard clinicaltreatment exists yet. The endocannabinoid system plays an important role in memory performance, being implicatedin the pathophysiology of DS. Previously in the hosting laboratory, cannabinoid type-1 receptor (CB1R) functionand expression were found enhanced in the hippocampus of young-adult trisomic (2-3 months old) Ts65Dn mice,the most used preclinical model of DS. A sub-chronic (7 days) pharmacological treatment with the CB1R antagonistrimonabant was observed to restore object-recognition memory in trisomic mice. Recently, the group found thatlong-term oral treatment with rimonabant also restored memory performance in middle-age (10 moths old) trisomicmice, an age when trisomic mice display a noticeable neurodegeneration, resembling Alzheimer’s disease observed inaged DS subjects. The purpose of the present study was to examine the neurodegenerative phenotype of trisomicmice after the long-term pharmacological inhibition of CB1R. A semi-automatic quantification method was developedto analyze cellular features from brain histological preparations. Analysis of locus coeruleus noradrenergic neuronsshowed a significant loss in trisomic mice that was not prevented by rimonabant. Cholinergic neurodegenerationwas not prevented by the treatment, and was only found in the medial septum, but not in other basal forebrainareas of trisomic mice. Together, despite the proven beneficial effects of rimonabant in memory performance, noeffect of treatment was observed in the neurodegenerative phenotype of trisomic mice which clearly dissociates thepro-cognitive effect of rimonabant from the possibility of preventing neurodegeneration.

Keywords: Down syndrome, Endocannabinoid system, Cannabinoid type-1 receptor, Cholinergic neurons,Adrenergic neurons.

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Tomas Berjaga Buisan

Neuronal basis of brain hypersynchronization in absence seizures: a computational study

Supervisor(s) Referee 1 Referee 2

Garcıa-Ojalvo, JordiCasanı, Pablo

Clusella, Pau Sancristobal, Belen

Abstract: Absence seizures are generalized epileptic seizures mainly diagnosed and prevalent in children and arecaused by abnormal electrical brain activity. These seizures initiate in layer 5/6 of the primary somatosensory cortexand are associated with genetic-based channelopathies. More than thirty mutations in genes encoding T-type calciumchannels, with a gain-of-function profile, have been linked to absence epilepsy. These channels are the actual front-line treatment target and have been identified in the axon initial segment (AIS) of the above-mentioned primarysomatosensory layer 5 pyramidal cells, a domain that plays a major role in neuronal excitability. AIS T-type calciumchannels are crucial for bursting so that any perturbation could potentially lead to epileptogenesis through increasedsynchronicity. This thesis aims to understand how T-type calcium channels located in the AIS of neurons lead tobursting, and how such bursting affects brain oscillations and their synchronization in the somatosensory cortexnetwork. We have designed and implemented a computational model that will enable us to understand the basicneural mechanisms underlying hypersynchronization states in the initiation foci of absence epileptic seizures. Todo that, we describe mathematically somatosensory pyramidal neurons with a compartmentalized integrate-and-firemodel, extended to include AIS T-type calcium channels. We also connect these neurons to the two main corticalinterneurons populations via conductance-based synapses. Our results show that an upregulation of the T-typecalcium channel leads to an increase in synchronized activity in local cortical networks in different oscillatory regimes,explaining how these channels could be responsible for hypersynchrony and seizure initiation.

Keywords: Absence Seizures, Somatosensory Cortex, Bursts, Synchronization, T-type

Valentina Pasker Gonzalez

Quantification of Learning in an Augmented Reality Training System Prototype for MinimallyInvasive Fetal Surgeries

Supervisor(s) Referee 1 Referee 2

Ceresa, Mario Piella, Gemma Mill, Jordi

Abstract: Twin-to-twin transfusion syndrome (TTTS) is a serious condition that may occur to around 15% ofpregnancies, in which two or more fetuses share the same placenta. It is characterized by abnormal connections in thevascular hemisphere (anastomoses) that cause blood to flow unevenly between the fetuses, leading to serious hazardsfor their growth and development. If left untreated, perinatal mortality occurs in 90% of cases, whilst neurologicalinjuries are still present in TTTS survivors.Minimally invasive intrauterine laser surgery is the standard and optimal intervention for this condition but is tech-nically challenging and can lead to complications. To obtain successful results, an accurate preoperative planning isvital for the TTTS cases. During this thesis, a prototype for a training system application is created, in which theclinician can interact with previously recorded minimally invasive fetal surgeries and manipulate the mother’s wombby using augmented reality (AR). The contributions to this project are: 1.Assembly of the registration system withcameras and processing to make it transferable to AR. 2. Quantification of the training rate with transferable tasksto the operating room. 3. Revision of the ground truth database for the segmentation models of the wombs usedfor the training.

Keywords: Twin-to-Twin Transfusion Syndrome, Surgical Training, Deep Learning, Unreal Engine, Augmentedreality

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