Aujourd’hui, l’usage des données lié aux services et contenus proposés sur Internet est en croissance continue et les opérateurs de télécommunications font face à une demande croissante en connectivité. Dans ce contexte, il est indispensable que la transition vers les réseaux très haut débit soit gérée de manière efficace afin de préserver, voire incrémenter, le niveau de concurrence sur le marché ainsi que maximiser l’investissement efficace au bénéfice des consommateurs à travers une combinaison appropriée de différentes formes de concurrence, de différentes technologies et d’investissement à la fois privé et public. Si accompagnée de manière efficace, cette transition peut représenter une grande opportunité pour les marchés des télécommunications européens, les transformant en marchés modernes et concurrentiels et permettant à la régulation ex ante de se retirer progressivement. Nous passons en revue les cadres institutionnels et réglementaires pour les réseaux d’accès fixes de nouvelle génération implémentés en France, Allemagne, Italie, Royaume-Uni et Espagne. A partir d’un modèle de concurrence calibré, nous simulons l’évolution des marchés à horizon 2050 et analysons dans quelle mesure ces cadres paraissent efficaces afin de restituer les meilleurs résultats pour le secteur et pour les consommateurs. Les résultats de notre modèle calibré suggèrent que, afin d’obtenir des meilleurs résultats en terme de bien-être total de long-terme, dans des proportions plus ou moins grandes, certains ajustements pourraient être introduits dans les cadres institutionnels et réglementaires considérés.Nous formulons ainsi, pour chacun des pays analysés, des recommandations visant à accélérer la couverture en très haut débit et à améliorer le niveau de concurrence. / Today, data usage driven by content and service providers over the Internet is constantly increasing and telecoms operators are expected to meet an increasing demand for connectivity. In this context, it is vital that the transition between legacy and ultrabroadband networks is properly managed in order both to preserve or improve the state of competition in the market and to maximize efficient investment to the benefit of consumers through an appropriate combination of different forms of competition, of different technologies and of private and public investment. If properly accompanied, the transition from legacy to next generation access networks can represent a major opportunity for the current European telecommunications markets, definitively transforming them into competitive and modern markets and allowing ex ante regulation to progressively step-back.We review the institutional and regulatory frameworks for fixed next generation access networks currently implemented in France, Germany, Italy, United Kingdom and Spain. Based on a calibrated competition model, we simulate market evolution up to 2050 and appraise to what extent these frameworks seem effective in order to achieve the best long-term results both for the industry and for consumers. The results of our calibrated model suggest that, to a greater or lesser extent, some adjustments might be introduced in the above-mentioned frameworks in order to achieve better outcomes in terms of total welfare in the long run. For each of the countries reviewed, we formulate policy recommendations aimed to accelerate NGA coverage and to improve the state of competition in ultrabroadband.

Introduction : Les dyschromies cutanées en mosaïque ont fait suspecter de longue date l’implication d’un mosaïcisme génétique sous-jacent. Ces évènements post-zygotiques sont cependant difficilement détectables par les techniques conventionnelles. Ainsi, les bases génétiques des dyschromies en mosaïque étaient restées mal connues. Matériel et méthodes : la cohorte M.U.S.T.A.R.D rassemble des échantillons d’ADN de biopsies cutanées de patients porteurs d’un mosaïcisme pigmentaire. Après une analyse phénotypique spécialisée, ces échantillons sont étudiés en séquençage à forte profondeur, d’exome (ES) en trio, ou ciblé. Les données sont analysées à l’aide d’un pipeline dédié, permettant la détection de variations ponctuelles en mosaïque (mSNV) mais également de diverses anomalies chromosomiques en mosaïque. Résultats : De 2013 à 2019, 101 patients ont été inclus. Un ES a été réalisé pour 56 patients, identifiant un mSNV chez 12 patients, dans 7 gènes dont 4 nouveaux (RHOA, DOCK1, GNA13, TFE3), et une anomalie chromosomique chez 17 patients. Une étude ciblée de ces gènes chez 40 autres patients était positive pour 17, soit un rendement diagnostique global à 55% (46/84). Conclusion : Ce travail illustre l’importance d’une approche bioinformatique polyvalente, combinée à une expertise clinique, pour la détermination des causes génétiques des dyschromies cutanées en mosaïque. Il a également mis en évidence le rôle de la voie de signalisation dépendant des Rho GTPases, faisant progresser notre compréhension de la physiopathologie des dyschromies en mosaïque, une étape nécessaire à l’amélioration de la prise en charge de ces patients porteurs de maladies rares et complexes. / Introduction: Mosaic cutaneous dyschromia is strongly evocative of an underlying genetic mosaicism. These post-zygotic events are challenging for conventional diagnostic tools. Thus, genetic basis of mosaic cutaneous dyschromia still remained poorly understood. Materials and Methods: The M.U.S.T.A.R.D. cohort gathers DNA from skin biopsies of patients with mosaic cutaneous dyschromia. After a specialised phenotype analysis, they are referred to either trio exome sequencing (ES) at 200X, or targeted ultra-deep sequencing (60,000X) of candidate genes. Data are analysed with a tailored pipeline, allowing detection of both low-rate nucleotidic variations or chromosomal events. Results: From 2013 to 2019, 101 patients were included. ES was performed for 56, with identification of mosaic SNV in 12 patients in 7 new genes, including 4 new genes (RHOA, DOCK1, GNA13, TFE3), and mosaic chromosomal anomalies in 17 patients. A targeted sequencing of these genes was performed for 40 more patients, with a confirmed mosaic SNV in 17, and a global diagnostic yield of 55% (46/84). Conclusion: This work highlights the importance of a versatile bioinformatic approach combined to a clinical expertise, to decipher the chromosomal and molecular aetiologies of developmental anomalies with mosaic cutaneous dyschromia. It also pinpoints the role of the Rho GTPase pathway, which will help enhancing our understanding of mosaic cutaneous dyschromia, and may ultimately result in better patients’ care.

Gut microbiota is considered an important factor in the development of various diseases including inflammatory bowel disease (IBD, n = 127), Ulcerative colitis, Crohn's disease, and colorectal cancer (CRC, n = 64). A part of this thtesis is to prepare clinical material of different sorts (stool, biopsy) for sequencing on Illumina Miseq platform. This is achieved trough DNA isolation, amplification of 16S and internal transcribed spacer (ITS), normalization and ligation of sequencing adaptors. The aim of this project is to describe the differences between microbiota in healthy and diseased subjects in case of IBD or unimpaired and tumorous tissue for CRC patients. This research is also being based on cultivation, where a fresh stool samples (n = 3) are cultivated in a broad range of conditions, which enables us to obtain ecophysiological and species diversity of these samples by traditional and molecular methods. The cultivable fungi are also assigned reliable taxonomy by amplification of relevant genes (ITS1, β tubulin, second largest subunit of RNA polymerase II, RPB2) followed by both-sided Sanger sequencing. Selected species of fungi are processed into lysates, which are used for stimulation of mice macrofage cell line (RAW). Therefore the impact on immunity response is studied in vitro and...

Bakgrund: Intensivvård är en avancerad behandling med noggrann övervakning av kritiskt sjuka patienter. Patienterna är i ett utsatt läge och i beroendeställning av vårdpersonal såväl sina närstående. Tidigare studier tar upp vikten av delaktighet men utifrån ett patientperspektiv. Det har erfarits att närstående inte görs delaktiga i vården som de skulle kunnat vara. Det saknas även studier där närståendes delaktighet undersökts. Att vara närstående till en kritiskt sjuk person kan vara svårt och det är intensivvårdssjuksköterskans ansvar att göra de närstående delaktiga. Negativa effekter kan ske för de närstående som inte får vara delaktiga, så kallat “post-intensive care syndrom”. Syfte: Studiens syfte var att beskriva närståendes upplevelser av delaktighet i vården av en vuxen kritiskt sjuk person på intensivvårdsavdelningen. Metod: En systematisk litteraturstudie med kvalitativ ansats med 15 vetenskapliga artiklar. Artiklarna har analyserats med hjälp av Bettany-Saltikov och McSherrys metod. Resultat: I resultatet framkom tre huvudkategorier: Att finnas till för patienten, Involverad i kommunikationen med vårdpersonal samt Delta i den fysiska omvårdnaden. Slutsats: Närståendes upplevelse av delaktighet har en betydande roll för intensivvården. Närstående känner sig delaktiga genom att få vara med fysiskt i omvårdnaden men även att vara passiv. De uppskattar att få information, att få valmöjligheter och på så sätt känna sig delaktiga. Närståendes delaktighet speglades även när de var nära, uppmuntrade och förde patientens talan. Att ta vara på närstående och göra dem delaktiga på intensivvårdsavdelningen är något att ta lärdom av. / Background: Intensive care involves an advanced treatment and close monitoring of critically ill patients. Patients are in a vulnerable position that depends on both their next-of-kin as well as advanced health care. Previous studies address the importance of participation but from a patient perspective. Former experiences from intensive care have pinpointed that relatives are not as involved in the care as they could be. There currently are few studies where the participation of relatives has been investigated. Being close to a critically ill person can be difficult and it is the intensive care nurse´s responsibility to involve the relatives. Negative effects can occur for the relatives who are not allowed to participate, so called “post-intensive care syndrome”.  Aim: The aim of the study was to describe relatives' experiences of participation in the care of an adult critically ill person in the intensive care unit. Method: A systematic literature study with a qualitative approach from 15 scientific articles. The articles have been analyzed using Bettany-Saltikov and McSherry´s method. Results: The results showed three main headings: To be there for the patient, Part taking in the communicational aspects with the care givers and Participate in physical care. Conclusion: Relatives' experience of participation has a significant role for intensive care. Relatives feel involved by being physically engaged in the care, but also by being passively active. They appreciate recieving information, having choices and through that feeling more involved. The participation of relatives was also reflected when they were close, encouraged and brought the patient´s voice. Taking care of relatives and making them involved in the intensive care unit is something to learn from.

A geological repository for spent nuclear fuel (SNF) and an associated encapsulation facility will be built in Sweden.  The encapsulation facility is planned to be in operation in 2025 and it will be the last place where verifying safeguards measurements of SNF can be performed. It is not clear what types of measurements that will be performed, because such requirements are not yet posed by national and international authorities and inspecting organizations. This report describes the objective and most recent results of a master thesis project, whereby a few existing non-destructive assay techniques for verifying SNF are selected for a review. The study focuses on the verifying ability of different techniques, or system of techniques in relation to the requirement that may be put on the future encapsulation plant. In addition, possible needs for future simulations and measurements are discussed. The work is done as a collaboration between Uppsala University in Sweden and Los Alamos National Laboratory in the USA.

L’arrivée récente de l’immunothérapie a bouleversé la prise en charge des cancers broncho-pulmonaires non à petites cellules (CBNPC). Le nivolumab, anticorps inhibiteur du point de contrôle immunitaire PD-1, a montré des résultats remarquables en deuxième ligne métastatique après échec des chimiothérapies standards de première intention. Cependant, seul un quart des patients tire un bénéfice durable de la prise de ce traitement. `A ce jour, aucun biomarqueur prédictif de l'efficacité thérapeutique du nivolumab n'a pu être identifié de manière claire et consensuelle. La recherche de biomarqueurs prédictifs de bénéfice ou de résistance à ce traitement répresente donc un enjeu majeur.L’apparition du séquençage à haut débit au cours de la dernière décennie a eu un impact considérable sur la recherche clinique et fondamentale, permettant d’appréhender la génétique d’une tumeur dans son ensemble. Ces nouvelles techniques s’ajoutent à d’autres déjà éprouvées telles que l’immunophénotypage ou l’immunohistochimie à disposition des chercheurs pour une analyse extensive des caractéristiques de la tumeur et du patient.L’objectif de ce travail a été d’identifier des marqueurs prédictifs d’efficacité du nivolumab dans le traitement des CBNPC avancés au moyen de ces différentes technologies. Pour cela, notre étude s'est alors intéressée à une cohorte multicentrique de 115 patients atteints de CBNPC et traités par nivolumab en deuxième ou troisième ligne métastatique après échec d'un doublet cytotoxique. Dans les limites de disponibilité et de qualité des échantillons, les profils génétique, transcriptomique et immunohistochimique de la tumeur ainsi que les profils clinique et immunologique des patients ont été analysés.Nos résultats mettent en évidence des marqueurs prédictifs majeurs de réponse au nivolumab. Ainsi, une bonne réponse au doublet cytotoxique de première intention favorise une efficacité optimale du nivolumab en ligne ultérieure. Par ailleurs, un contrôle régulier de l'évolution des cellules myéloïdes immunosuppresives et des cellules cytotoxiques exprimant TIM-3 d'un patient permet de détecter une résistance primaire ou secondaire au traitement. D'autre part, l'estimation conjointe des expressions des protéines PD-L1 et CD8 par séquençage d'ARN constitue un marqueur prédictif majeur de réponse. Sa capacité prédictive surpasse celle de l'estimation de PD-L1 seule et celle d'autres signatures transcriptomiques précédemment établies et composées d'un nombre plus important de gènes. Enfin, l'étude des séquençages d'exome des tumeurs montre l'importance d'une analyse étendue de la génétique tumorale et la nécessité de ne pas se limiter à l'estimation de sa charge mutationnelle.Dans ce travail, nous avons pu mettre en évidence des marqueurs prédictifs d'efficacité du nivolumab dans le traitement des CBNPC avancés. Nos résultats soulignent l'importance de l'utilisation de plusieurs technologies pour la caractérisation de la biologie tumorale et de l'immunité du patient dans une démarche de découverte de biomarqueurs et de construction de modèles prédictifs d'efficacité des immunothérapies. / The recent introduction of immunotherapy has disrupted the management of non-small cell lung cancer (NSCLC). Nivolumab, an antibody targeting the immune checkpoint inhibitor PD-1, has shown remarkable results in seconde-line setting after failure of standard first-line chemotherapy. However, only a quarter of patients benefits from this therapy. To date, no predictive biomarker of the therapeutic efficacy of nivolumab has been identified in a clear and consensual manner. The research for predictive biomarkers of efficacy or resistance to this treatment is, therefore, a major challenge.The emergence of high-throughput sequencing over the past decade has had a significant impact on clinical and fundamental research, making possible to understand the genetics of a tumor as a whole. These new techniques are in addition to other already proven techniques such as immunophenotyping or immunohistochemistry available to researchers for extensive analysis of tumor and patient characteristics.The objective of this work was to identify predictors of the efficacy of nivolumab in the treatment of advanced NSCLC using these different technologies. To do this, our study focused on a multicentre cohort of 115 NSCLC patients treated with nivolumab in the second- or third-line after failure of a cytotoxic doublet. Within the limits of sample availability and quality, the genetic, transcriptomic and immunohistochemical profiles of the tumor as well as the clinical and immunological profiles of the patients were analysed.Our results highlight major predictive markers of response to nivolumab. Thus, a good response to the first-line cytotoxic doublet promotes optimal efficacy of subsequent online nivolumab. In addition, regular monitoring of the evolution of a patient's immunosuppressive myeloid cells and cytotoxic cells expressing TIM-3 can detect primary or secondary resistance to treatment. On the other hand, the joint estimation of PD-L1 and CD8 protein expressions by RNA sequencing is a major predictive marker of response. Its predictive capacity surpasses that of the PD-L1 estimate alone and that of other previously established transcriptomic signatures composed of a larger number of genes. Finally, the study of tumor exome sequencing shows the importance of extensive analysis of tumor genetics and the need not only to focus on the estimation its mutation burden.In this work, we were able to identify predictive markers of the efficacy of nivolumab in the treatment of advanced NSCLC. Our results highlight the importance of using several technologies for the characterization of tumor biology and patient immunity in a process of biomarker discovery and the construction of predictive models of the efficacy of immunotherapies.

As the field of next-generation sequencing (NGS) matures and the technology grows more advanced, it is becoming an increasingly strong tool for solving various biological problems. Harvesting and analysing the full genomic sequence of an individual and comparing it to a reference genome can unravel information about detrimental mutations, in particular ones that give rise to diseases such as cancer. At the Rudbeck Laboratory, Uppsala University, a fully automatic software pipeline for somatic mutational analysis of cancer patient sequence data is in development. This will increase the efficiency and accuracy of a process which today consists of several discrete computation steps. In turn, this will reduce the time to result and facilitate the process of making a diagnosis and delegate the optimal treatment for the patient. However, the genomic data of an individual is very sensitive and private, which demands that great security precautions are taken. Moreover, as more and more data are produced storage space is becoming increasingly valuable, which requires that data are handled and stored as efficiently as possible. In this project, I developed a Python pipeline for automatic compression and encryption of NGS alignment data, which aims to ensure full privacy protection of patient data while maintaining high computational and storage efficiency. The pipeline uses a state-of-the-art real-time compression algorithm combined with an Advanced Encryption Standard cipher. It offers security that meets rigorous modern standards, and performance which at least matches that of existing solutions. The system is made to be easily integrated in the somatic mutation analysis pipeline. This way, the data generated during the analysis, which are too large to be kept in operational memory, can safely be stored to disk.

Bakgrund: Personcentrerad omvårdnad är en av sjuksköterskans sex kärnkompetenser. Detta innefattar att bemöta olika personer. Trots detta upplever sjuksköterskor svårigheter med att bemöta anhöriga i den allmänna palliativa vården. Detta på grund av att sjuksköterskor upplever sig ha bristande kompetens inom området. Samtidigt uttrycker anhöriga en önskan att involveras i vården. Syfte: Att belysa anhörigas upplevelser vid vård i livets slutskede. Metod: Totalt 14 kvalitativa artiklar som fokuserar på anhörigas upplevelser vid vård i livets slutskede identifierades och analyserades för att finna gemensamma teman. Resultat: Fyra huvudteman identifierades. Vikten av sociala relationer samlar anhörigas upplevelser kring mellanmänskliga relationer med sjuksköterskan, patienten men även relationen till sig själv. Vikten av att vara delaktig handlar om hur vården kan påverkas genom anhörigas upplevelser och kunskap. Vikten av god vård för patienten påvisar att patienters upplevelser påverkar anhöriga. Vikten av att ta hand om sig själv beskriver olika sätt att som anhöriga kunna anpassa sig till vård i livets slutskede. Konklusion: Eftersom både anhöriga och sjuksköterskor upplever svårigheter i mötet krävs utökad kompetens hos sjuksköterskan för att kunna bemöta anhöriga vid vård i livets slutskede. / Background: Person-centred care is one of the nurses six core competencies. Which includesmeeting different people. Despite this fact nurses’ experiences difficulties when meeting next of kins in general palliative care. This is caused by nurses’ lack of competence in the field. While next of kins expresses a wish to be involved in caring. Aim: To illustrate next of kins experiences in end-of-life care. Method: A total of 14 qualitative articles which focuses onnext of kins experiences of end-of-life care were identified and analysed in order to findcommon themes. Results: Four main themes were identified. The importance of social relationships gathers next of kins experiences of interpersonal relationships with nurses, the patient but also the relationship to oneself. The importance of being involved focus on how care can be affected by next of kins experiences and knowledge. The importance of good carefor the patient demonstrates that patients’ experiences affect next of kins. The importance of selfcare describes different ways next of kins can adapt to end of life care. Conclusion: Expanded competency in nurses is demanded, since both next of kins and nurses experience difficulties in encounters in end-of-life care.

Bakgrund: Plötslig död är ett svårdefinierat begrepp då det kan orsakas av många faktorer. Att hantera plötslig död och sorg som sjuksköterska samt att bemöta anhöriga i dessa situationer är utmanande. Sorgereaktioner är individuella och kan skilja sig mycket från person till person. Det är oftast sjuksköterskor som etablerar kommunikationen mellan anhöriga och vårdteamet vilket ställer höga krav på professionen. Syfte: Beskriva sjuksköterskors upplevelser av att bemöta anhöriga i sorg efter plötsliga dödsfall som inträffat inom akutsjukvård.Metod: En litteraturöversikt med kvalitetsgranskade kvalitativa artiklar från åren 2012–2021. Artikelsökningar gjordes i databaserna; Cinahl, Medline och PubMed. Analysen gjordes utifrån Fribergs (2017) beskrivning av en femstegs analys. Resultat: I resultatet framkom tre teman: Emotionell påverkan (Känslomässiga aspekter, känslor av misslyckande och otillräcklighet samt otrygg i mötet), Kommunikation (Informerande samtal och bygga goda relationer) samt Arbetsmiljö (Tidsbrist och samverkan i team). Slutsats: Sjuksköterskor upplevde mötet med anhöriga vid plötslig död som komplicerat. Bristfällig kunskap inom ämnet sågs som ett problemområde. Att ge möjlighet för sjuksköterskor att utveckla sina färdigheter genom utbildningar kring bemötande vid sorg skulle kunna medföra en hälsosammare arbetsmiljö för sjuksköterskan. Ökad utbildning skulle också kunna ha betydelse för kvalitén på vården då det gäller stöd till anhöriga. / Title: The nurse`s meeting with relatives in the event of sudden death: A qualitative literature review Background: Sudden death is a difficult concept to define as it can be caused by many factors. Dealing with sudden death, relatives and bereavement as a nurse is challenging. Reactions in bereavement are individual, it can differ between people. It is the nurse who often establishes the communication between relatives and healthcare, which places high demands on the nurse. Aim: Describe nurses´ experiences of treating relatives in bereavement after sudden deaths that occurred in emergency care. Method: A literature review was performed with a base in quality reviewed qualitative articles from the years 2012-2021. Searches of articles were made in databases Cinahl, Medline and PubMed. The analysis was based on a five-step analysis described by Friberg (2017).Result: The result revealed three themes: Emotional impact (Emotional aspects, feelings of failure and inadequacy and insecurity during the meeting), Communication (Informative conversations and create good relations) and Work environment (Lack of time and team collaboration). Conclusion: Nurses experienced the meeting with bereaved relatives after sudden death as complicated. Lack of knowledge in the subject was seen as a problem. Providing opportunities for nurses to develop their skills through education in bereavement could lead to a healthy work environment and a healthcare with high quality to support relatives.

Bakgrund: En stor del av patienterna som avlider på intensivvårdsavdelningar gör detta efter att ett beslut tagits att avstå eller avbryta livsuppehållande behandling. Närstående kan påverkas på olika sätt när vården går från kurativ till palliativ, bland annat kan upplevelser av bristande kommunikation från personalen leda till psykiska symtom i efterförloppet. Intensivvårdssjuksköterskor har beskrivit osäkerhet gällande processen vid övergång till palliativ vård och önskat mer kunskap för att förbättra stöd till närstående. Syfte: Att undersöka närståendes upplevelser av transitionen när patientens vård övergår från kurativ till palliativ på en intensivvårdsavdelning. Metod: Kvalitativ litteraturöversikt med systematisk ansats. 15 artiklar baserade på intervjuer som beskriver upplevelser av att vara närstående till en patient där vården övergått från kurativ till palliativ på en intensivvårdsavdelning analyserades enligt Evans (2002) beskrivande syntes. Resultat: Studiernas innehåll kunde sammanfattas i fem huvudteman: ”Att möta döden”, ”Behov av information”, ”Upplevelser av bemötande”, ”Beslutsprocessen” och ”Dödsvakan”. Slutsats: Närstående har behov av tydlig, frekvent och ärlig information för att underlätta transitionsprocessen, men under chockfasen kan de ha svårt att hantera informationen. Genuin, empatisk omvårdnad och stöd, att få vara involverad i beslutsprocessen utan att ha ensamt ansvar samt att få vara närvarande och delaktig under dödsvakan anses mycket betydelsefullt. Ökad kunskap om närståendes behov under transitionen från kurativ till palliativ vård kan underlätta för sjuksköterskors stödjande arbete. / Background: A large proportion of the patients who die at intensive care units do so after a decision has been made to withhold or withdraw life-sustaining treatment. The next of kin can be affected in various ways when care goes from curative to palliative, among other things, experiences of lack of communication from the staff can lead to psychological symptoms in the aftermath. Intensive care nurses have described uncertainty regarding the process of transition to palliative care and wanted more knowledge to improve support for next of kin. Aim: To investigate the next of kins' experiences of the transition when the patient's care is shifted from curative to palliative in an intensive care unit. Method: Qualitative literature review with a systematic approach. 15 articles based on interviews describing experiences of being close to a patient where care has shifted from curative to palliative in an intensive care unit were analyzed according to Evans' (2002) descriptive synthesis. Results: The content of the studies could be summarized in five main themes: “Meeting death”, “Need for information”, “Experiences of treatment”, “The decision-making process” and “The vigil of death”. Conclusion: Next of kin need clear, frequent and honest information to facilitate the transition process, but during the shock phase they may have difficulty handling the information. Genuine, empathetic care and support, being involved in the decision-making process without having sole responsibility and being able to be present and involved during the vigil is considered very important. Increased knowledge of the needs of next of kin during the transition from curative to palliative care can facilitate nurses' supportive work.