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Skin microbiome engineering: new generation of therapeutics: engineering Cutibacterium acnes to treat skin conditions
No full textWe are living in a symbiotic relationship with our Microbiome. This relationship with our microbes can become opportunistic and lead to dysbiosis. While we were previously treating dysbiosis with antimicrobial drugs, we removed not only pathogenic but also beneficial microbes unselectively. Domesticating commensal microbes for the production of
therapeutics poses a new perspective on therapy. Life therapeutics can address unmet clinical needs by being targeted, efficient and reducing side effects associated to current treatments. Here we developed diverse tools to domesticate Cutibacterium acnes, the most abundant skin commensal inhabiting the hostile environment of the pilosebaceous unit. We propose its usage against common skin conditions and showed on the example of acne vulgaris its probiotic potential as an engineered living drug.Estem vivint en una relació simbiòtica amb el nostre Microbioma. Aquesta relació amb la nostra flora pot arribar a ser oportunista i conduir a la disbiosi. Mentre que anteriorment es tractava la disbiosi amb fàrmacs antimicrobians, fet que eliminava no només microbis patògens sinó també beneficiosos de manera no selectiva. Domesticar microbis comensals per a la producció de terapèutics proposa una nova perspectiva de teràpia. Aquestes medicines vives poden abordar necessitats clíniques no satisfetes en ser dirigida, eficient i amb menors efectes secundaris associats amb els tractaments actuals. Aquí hem desenvolupat diverses eines per domesticar Cutibacterium acnes, el comensal de la pell més abundant que habita l’entorn hostil de la unitat pilosebàcia. Proposem el seu ús contra afeccions comunes de la pell i demostrem amb l’exemple de l’acne vulgar el seu potencial probiòtic com a fàrmac viu.Programa de Doctorat en Biomedicin
Study on group-oriented AR experiences: comparing Smartphone AR and ARML
No full textTreball fi de màster de: Master in Cognitive Systems and Interactive MediaSupervisor: Narcís ParésAugmented Reality (AR) has become an increasingly popular technology across many different industries, particularly in education and cultural heritage. Over the years, AR has been integrated with various devices. This thesis investigates the influence of device type and user role (holder, non-holder) on group dynamics in location-based augmented reality. The two devices this study focuses on are the AR Magic Lantern, a specially developed projection-based AR and a smartphone-based AR. While smartphone-based AR is widely used and accessible in successfully augmented physical spaces, it has been criticised for causing user isolation and making it difficult to share the experience with other users. In contrast, the AR Magic Lantern (ARML) allows for more shared and collaborative interactions, which can potentially enhance group collaboration and engagement. A group consisting of three to five users they were tested in two different scenarios. In one scenario, users interact with the AR content through a smartphone, and in the other through the AR Magic Lantern. In both scenarios, users may take turns holding the device. Both scenarios use the Garum Game, in which players interact with objects such as knives, spoons, and stirring sticks to make garum, an ancient Roman fish sauce. The findings show that the AR Magic Lantern (WaS paradigm) encourages stronger group dynamics and collaboration, as well as promoting higher intrinsic motivation, while smartphone AR (WoW paradigm) leads to quicker task completion but reduced social interactions. Holder status was found not to have a significant impact on group dynamics
Estudio e implementacion de Kyber y ́Dilithium
No full textDirector: Alvaro Montes Aranda ́Treball de fi de Grau en Enginyeria InformàticaKyber and Dilithium are encryption and digital signature schemes selected by NIST as post-quantum cryptography standards. Both base their security on the complexity of some lattice problems over polynomial rings, which allows for efficient implementations. This project takes a pedagogical approach to understanding cryptographic systems in the post-quantum era. The goal is to comprehend and implement Kyber and Dilithium from scratch using the computational language SageMath. To optimize polynomial multiplication, we will use the Number Theoretic Transform based on the Chinese Remainder Theorem. During the project, implementation related challenges were encountered and documented, as well as the solutions applied to program a clean demonstration of Kyber and Dilithium.Kyber y Dilithium son esquemas de cifrado y firma digital seleccionados por el NIST como estandares de criptografía post-cuantica. Ambos basan su seguridad en la complejidad de algunos problemas de retíıculos sobre anillos de polinomios, lo que permite implementaciones eficientes. Este proyecto adopta un enfoque pedagogico para la comprensión de los sistemas criptograficos en la era post-cuántica. El objetivo es entender e implementar ́ Kyber y Dilithium desde cero utilizando el lenguaje computacional SageMath. Para optimizar la multiplicacion de polinomios usaremos la Transformada Teórica de Numeros basada en el Teorema Chino del Resto. Durante el proyecto, se encontraron y documentaron los desafíos relacionados con la implementacion, así como las soluciones aplicadas para programar una demostracion limpia de Kyber y Dilithium.Kyber i Dilithium son esquemes de xifrat i signatura digital seleccionats pel NIST com a estandards de criptografia post-quàntica. Tots dos basen la seguretat en la complexitat d’alguns problemes de reticles sobre anells de polinomis, cosa que permet implementacions eficients. Aquest projecte adopta un enfocament pedagogic per al coneixement dels sistemes criptografics a l’era post-quàntica. L’objectiu ès comprendre i implementar ́Kyber i Dilithium des de zero fent servir el llenguatge computacional SageMath. Per optimitzar la multiplicacio de polinomis farem servir la Transformada Teórica de Numeros basada en el Teorema Xin ́ es de la Resta. Durant el projecte, es van trobar i documentar els desafiaments relacionats amb la implementacio, així com les solucions aplicades per programar una demostracio neta de Kyber i Dilithium.
La terminología floral: variación terminológica y estandarización comercial en el sector de flores cortadas
No full textEl desenvolupament de la indústria de les flors tallades ha aconseguit una notorietat considerable dins de l'àmbit econòmic mundial com a sector emergent. Xina i Espanya són al centre del creixement d'aquest sector, amb unes necessitats i uns obstacles terminològics ben evidents tant per a la producció local com per al comerç internacional. La terminologia de les flors està relacionada amb àmbits científics ben consolidats, com la botànica, la medicina i la farmacologia. Per altra banda, la terminologia de les ciències naturals enriqueix un panorama lèxic històricament variat, ja que les llengües disposen d'un lèxic molt divers dialectològicament per a denominar plantes o animals. Davant d'aquesta variació tan alta, les necessitats de la indústria i el comerç demanen processos d'estandardització no coincidents amb l'estandardització científica. A més, a Xina tenim més de vint procediments diferents per a denominar les plantes, per la qual cosa no ens hauria de cridar l'atenció que una mateixa planta rebi moltes denominacions diferents. Aquest sector emergent compte cada dia amb més neologismes, que exerceixen influències positives o negatives en el panorama de la variació terminològica del sector. Aquesta tesi, basada en els estudis descriptius realitzats sobre la terminologia floral i en recerques in situ (mercats i professionals), permet analitzar les necessitats terminològiques del sector a Xina i a Espanya, construir un recurs terminològic que serveixi per a l'estandardització d'aquest sector, i caracteritzar l'estandardització per al comerç tan nacional com internacional, de manera distinta de l'estandardització lingüística, de la científica i de l'estandardització industrial tal como està regulada en organismes com la ISO.El desarrollo de la industria de las flores cortadas ha llegado a alcanzar una considerable notoriedad dentro del ámbito económico mundial como sector emergente. China y España también están en el centro del desarrollo de este sector, con unas necesidades y obstáculos terminológicas muy evidentes tanto para la producción local como para el comercio internacional. La terminología de las flores está relacionada con ámbitos científicos bien consolidados, como la botánica, la medicina y la farmacología. Por otro lado, la terminología de las ciencias naturales enriquece un panorama léxico históricamente variado: las lenguas disponen de léxico muy variado dialectológicamente para denominar plantas o animales. Ante esta variación tan elevada, las necesidades de la industria y el comercio demandan procesos de estandarización que no tienen porqué coincidir con la estandarización científica. Además, en China disponemos de más de veinte procedimientos para denominar las plantas, por lo cual no debería resultarnos llamativo que una misma planta reciba muchas denominaciones distintas. Este sector emergente cuenta cada día con más neologismos, que ejercen influencias tanto positivas como negativas en el panorama de la variación terminológica del sector. Este proyecto de tesis se base de estudios descriptivos e investigaciones in situ que permita analizar las necesidades terminológicas del sector en China y en España, construir un recurso terminológico que sirva para la estandarización de este sector, y caracterizar la estandarización para el comercio tanto nacional como internacional, de manera distinta de la estandarización lingüística y de la estandarización industrial tal como está regulada en organismos como la ISO.The development of the cut flower industry has achieved considerable notoriety in the world economy as an emerging sector. China and Spain are also at the centre of the development of this sector, with very obvious terminological needs and obstacles for both local production and international trade. Flower terminology is related to well-established scientific fields, such as botany, medicine, and pharmacology. On the other hand, the terminology of the natural sciences enriches a historically varied lexical panorama: languages have a dialectologically varied lexicon to name plants or animals. Given this high variation, the needs of industry and commerce demand standardization processes that do not have to coincide with scientific standardization. In addition, in China we have more than twenty procedures for naming plants, so it should not be surprising that the same plant receives many different names. This emerging sector has more neologisms every day, which exert both positive and negative influences on the panorama of terminological variation in the sector. This thesis, based on descriptive studies on floral terminology and in-situ investigation, allows us to analyze the terminological needs of the sector in China and Spain, to build a terminological resource that can be used for the standardization of this sector, and to characterize standardization for both national and international trade, in a different way from linguistic standardization, scientific standardization and industrial standardization as regulated by organizations such as the ISO.Programa de Doctorat en Traducció i Ciències del Llenguatg
La atención al parto en diferentes países de la Organización para la Cooperación y el Desarrollo Económico (OCDE)
No full textEl desarrollo científico-tecnológico ha comportado una progresiva medicalización del proceso de embarazo, parto y puerperio y la institucionalización de la atención al parto en los hospitales en la mayoría de países industrializados. Existen diferentes modelos organizativos y de atención al parto y se pueden encontrar diferencias en cuanto a los resultados de esta atención. Objetivo: Describir diferentes modelos organizativos y de atención al parto en países seleccionados de la Organización para la Cooperación y el Desarrollo Económico (OCDE) e identificar variaciones en la estructura organizativa de los modelos observados. Metodología: Búsqueda bibliográfica y cuestionario a informantes clave de diferentes países para identificar los aspectos relevantes sobre financiación de los servicios, lugar en que se presta la atención y distribución de competencias. Resultados: Se describe la organización y el modelo de atención al parto, en el contexto de los sistemas de salud de cada país. Países incluidos: Reino Unido, Australia, Holanda, Irlanda, Francia, España y Canadá. Se presentan indicadores de la OCDE sobre la actividad sanitaria, el comportamiento del sistema de salud y el estado de salud de la población. Conclusiones: Se observan diferentes formas de organizar la atención a la maternidad entre los países seleccionados y se evidencian diferencias.Scientific and technological advances have entailed an increased influence of medicine in the process of pregnancy, childbirth and post-partum with the institutionalisation this entails for childbirth care in the hospitals of most industrialised countries. Several organisational and childbirth care models are in place and differences can be observed between them with regard to the outcomes of such care.
Aim: To describe differing organisational and childbirth care models in the chosen countries of the Organization for Economic Co-operation and Development (OECD) and identify variations in the organisational structure of the models observed.
Methodology: To conduct a bibliographical search and questionnaire on key informers from various countries to identify relevant aspects concerning service funding, care settings and distribution of authority in this sphere.
Results: A description is given of the organisation and childbirth care model on the context of the health systems of each country. The countries studied are: Australia, Canada, France, Ireland, the Netherlands, Spain and the United Kingdom. OECD indicators are presented on healthcare activity, the operation of the health system and the state of health of the population.
Conclusions: Several forms of organising maternity care have been observed from the countries chosen and differences have been identified in the outcomes of care. There are numerous kinds of settings for providing care to women with a low obstetric risk during the maternityprocess. In the healthcare systems analysed, care for women during pregnancy is often provided in a non-hospital setting; however, when it comes to childbirth care, several options are available in terms of the setting and care which can even be chosen by women themselves in certain cases. The indicators selected point to a broad range of results among the chosen countries and it would be appropriate to research the possible link between this variation in terms of the kind of organisation and care provided during maternity and, accordingly, to identify common criteria relating to specific aspects in care for women with low obstetric risks
Multidimensional studies of depression and antidepressant response : behavioural models, molecular and structural approaches
No full textDepression is a major public health problem, affecting 322 million people worldwide. Antidepressants are the basis for the treatment of major depression. Although increasingly safer, individual patient response variability and treatment outcome is highly variable. The objective of this thesis was to unravel the mechanism of early and total antidepressant response, in a novel multidimensional approach. The behavioural analysis of an animal model of depression and antidepressant response, allowed the development of a treatment sub-population stratification method, and consequent antidepressant response behavioural characterization. A neurochemical evaluation of the mPFC, evidenced serotonergic and dopaminergic novel alterations between responders and non-responders to fluoxetine. Furthermore, the transcriptomic study of treatment subpopulations, expanded the implications of oligodendrocytes in the development of antidepressant response. Altogether, this thesis provides a new approach to the study of depression, as well as an expansion of the knowledge necessary to inform future prevention strategies, biomarker generation and therapeutic strategies.La depresión supone uno de los mayores problemas de salud pública a nivel mundial, afectando actualmente a 332 millones de personas globalmente. Los fármacos antidepresivos suponen la base del tratamiento de la depresión. En la presente tesis, se ha realizado una novedosa aproximación multidimensional del estudio de la depresión así como de la respuesta al tratamiento antidepresivo. La realización de estudios de comportamiento con modelos animales de depresión, ha permitido el desarrollo de un nuevo método de estratificación de sub-poblaciones derivadas de la respuesta tratamiento, así como la caracterización comportamental longitudinal de estas. La evaluación neuroquímica de las sub-poblaciones, ha permitido identificar alteraciones en la transmisión serotonérgica y dopaminergica diferenciales, del mPFC de respondedores y no respondedores a fluoxetina. Además, el estudio transcriptómico de áreas implicadas en el desarrollo de la depresión, ha permitido identificar en los oligodendrocitos, elementos clave para la respuesta al tratamiento. En conjunto, la tesis aporta una nueva visión al estudio traslacional de la depresión, así como conocimiento que puede contribuir al desarrollo de estrategias de prevención, biomarcadores y nuevas estrategias terapéuticas.Programa de Doctorat en Biomedicin
Liquid biopsy for early tumor relapse detection : Development of hypersensitive genomic sequencing methodologies for the detection of ultra-rare genetic variants in the blood plasma of pediatric cancer patients
No full textThe profiling of circulating-tumor DNA (ctDNA) in blood plasma, often known as liquid biopsy, has recently
been of great interest in cancer research. This minimally-invasive strategy relies on the fact that ctDNA
represents, at least partially, the real-time state of the tumor genome and holds great potential for early
cancer detection and patient care. However, the fraction of ctDNA in total cell-free DNA (cfDNA) is often very
low and requires ultra-sensitive and specific methods for its detection. This thesis focuses on the
development and implementation of ultra-sensitive Next Generation Sequencing (NGS) methods that enable
the identification of rare variants in plasma in a specific way. In summary, this work presents a
comprehensive and cost-effective strategy for monitoring tumor mutations in the plasma of pediatric patients
in a personalized manner. Our strategy aims to provide a tool to anticipate the detection and treatment of
tumor relapses.L’anàlisi d'ADN tumoral circulant (ADNtc) al plasma sanguini, sovint conegut com a biòpsia líquida, ha
despertat recentment gran interès en la recerca del càncer. Aquesta estratègia mínimament invasiva es basa
en que l’ADNtc representa, almenys parcialment, l'estat en temps real del genoma del tumor i té un gran
potencial per a la detecció precoç del càncer. Tanmateix, la fracció d'ADNct en l'ADN lliure circulant (ADNlc)
total és sovint molt baixa i es requereixen mètodes ultra-sensibles i específics per a la seva detecció.
Aquesta tesi se centra en el desenvolupament i la implementació de mètodes ultra-sensibles basats en
tecnologies de seqüenciació massiva (NGS) que permetin la identificació de variants rares en plasma de
forma específica. En resum, aquest treball presenta una estratègia integral i rendible pel seguiment de
mutacions tumorals en el plasma de pacients pediàtrics de manera personalitzada. La nostra estrategia
pretén oferir una eina que permeti anticiparse en la detecció i tractament de recidives tumorals.Programa de doctorat en Biomedicin
Defective X-chromosome inactivation and cancer risk in women
No full textX-chromosome inactivation (XCI) is a fundamental mechanism in placental mammals that compensates for gene dosage differences between sexes. Using methylation levels of genes under XCI, we establish defective levels of XCI as a new source of interindividual variation among cancer types in females, characterized by a significant and consistent lowering of XIST expression and enrichment of differentially expressed genes under XCI. We show that defective XCI is an additive factor to the cancer risk of XCI escape deregulation in women. Defective XCI of more than 10% has an attributable risk of 40% among 12 different cancers from The Cancer Genome Atlas. Validations between independent studies of breast cancer samples show that defective XCI increases triple-negative subtype frequency, decreases survival rates, and is reduced by chemotherapy treatment. Mechanistically, it is associated with somatic mutations at TP53 and top MYC gains. In independent studies, defective XCI is detectable in blood and increases with aging, menopause, and cancer diagnosis
Cocreating the visualization of digital mobility outcomes: Delphi-type process with patients
No full textBackground: Recent technological advances in wearable devices offer new potential for measuring mobility in real-world contexts. Mobilise-D has validated digital mobility outcomes to provide novel outcomes and end points in clinical research of 4 different long-term health conditions (Parkinson disease, multiple sclerosis, chronic obstructive pulmonary disease, and proximal femoral fracture). These outcomes also provide unique information that is important to patients; however, there is limited literature that explores the optimal methods to achieve this, such as the best way to visualize patients' data. Objective: This study aimed to identify meaningful outcomes for each condition and how to best visualize them from the perspective of end users. Methods: Using a Delphi-type protocol with patients as subject matter experts, we gathered iterative feedback on the cocreation of visualizations through 3 rounds of questionnaires. An open-ended questionnaire was used in round 1 to understand what aspects of mobility were most influenced by their health condition. These responses were mapped onto relevant digital mobility outcomes and walking experiences and then prioritized for visualization. Using patient responses, we worked alongside researchers, clinicians, and a patient advisory group to develop visualizations that depicted a week of mobility data. During rounds 2 and 3, participants rated usefulness and ease of understanding on a 5-point Likert scale and provided unstructured feedback in comment boxes for each visualization. Visualizations were refined using the feedback from round 2 before receiving further feedback in round 3. Results: Participation varied across rounds 1 to 3 (n=48, n=79, and n=78, respectively). Round 1 identified important outcomes and contexts for each health condition, such as walking speed and stride length for people with Parkinson disease or multiple sclerosis and number of steps for people with chronic obstructive pulmonary disease or proximal femoral fracture. The consensus was not reached for any visualization reviewed in round 2 or 3. Feedback was generally positive, and some participants reported that they were able to understand the visualization and interpret what the visualization represented. Conclusions: Through the feedback provided and existing data visualization principles, we developed recommendations for future visualizations of mobility- and health-related data. Visualizations should be readable by ensuring that large and clear fonts are used and should be friendly for people with vision impairments, such as color blindness. Patients have a strong understanding of their own condition and its variability; hence, adding additional factors into visualizations is recommended to better reflect the nuances of a condition. Ensuring that outcomes and visualizations are meaningful requires close collaboration with patients throughout the development process.This work was supported by the Mobilise-D project that has received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking (JU; grant agreement 820820). This JU receives support from the European Union’s Horizon 2020 research and innovation program and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The content of the current publication reflects the authors’ view, and neither IMI nor the European Union, EFPIA, nor any associated partners are responsible for any use that may be made of the information contained herein. HG was supported by the Fraunhofer Internal Programs (grants Attract 044–602140 and 044–602150). HG also received institutional funding from the Deutsche Forschungsgemeinschaft (German Research Foundation)—SFB 1483—Project-ID 442419336, EmpkinS. LR, AY, and SDD were also supported by the IMI2 JU project IDEA-FAST (grant agreement 853981). LR, AY, and SDD were supported by the National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre based at The Newcastle upon Tyne Hospital National Health Service (NHS) Foundation Trust, Newcastle University, and the Cumbria, Northumberland, and Tyne and Wear NHS Foundation Trust and the NIHR/Wellcome Trust Clinical Research Facility infrastructure at Newcastle upon Tyne Hospitals NHS Foundation Trust. LR received funding from the NIHR Senior Investigator Awards (2020-2024 and 2024-2028). EB was supported by the NIHR Sheffield Biomedical-Research Centre and Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, or the Department of Health and Social Care
Age-related trajectories of health decline among immigrants and natives in Europe: the effect of education
No full textData de publicació electrònica: 29-11-2024Background: The ability to age healthily is highly dependent on individual characteristics that include gender, social class, a range of biological and contextual factors, and migrant background. Indeed, immigration has changed the demographic composition and social structure of many European countries, generating an increasing interest in how societies, and immigrants in particular, are aging. Research Design: This paper compares the age-related trajectories of health decline in three health measures (activity limitation indicator, self-perceived health, and chronic conditions) among 7,429 immigrants and 81,424 native-born populations aged 50 years old and over using longitudinal data from seven waves of the Survey of Health, Ageing and Retirement in Europe (SHARE) (2004-2020). Analysis: We use descriptive and multivariate models (random-effects regression models) to analyze the association between migration status and each health outcome. We are particularly interested in determining the age-related trajectory of this association across three levels of education, exploring at the same time the effect of the interaction between immigration status and age on health. Results: Our results highlight potential gaps in health between immigrants and native-born people that are particularly large for the low-educated group. In other words, the health decline is more marked for low-educated immigrants compared to native-born populations in particular for activity limitation indicator and self-perceived health, while it is less pronounced with the accumulation of chronic conditions. Conclusions: Our findings should serve to enhance the design of the provision of social services and support and the promotion of equal opportunities.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Aïda Solé-Auró obtained financial support for this research from the Spanish Ministry of Science and Innovation under the program "Generación de Conocimiento" Project LONGHEALTH (PID2021-128892OB-I00; PI: Iñaki Permanyer [CED-CERCA]; Aïda Solé-Auró [Universitat Pompeu Fabra]). This paper received support from the 2021 SGR 00957 project (PI: Aïda Solé-Auró) funded by the Agency for Management of University and Research Grants (AGAUR). Isabel Sáenz-Hernández acknowledges funding from the Investigo Program (funded by Next Generation EU, 2023; ref. BDNS 664047)