Bakgrund: Datorspel kan ge en ökad dagtrötthet och försämrad sömnkvalitet hos individer som spelar mer än 2h/dag. Fysisk aktivitet har en akut positiv inverkan på många delar i sömnen såsom sömnkvalitet och dagtrötthet. Syftet med studien var att kartlägga den fysiska aktivitetsnivån och sömnsvårigheter hos datorspelande vuxna, samt undersöka ett eventuellt samband mellan fysisk aktivitet och sömnsvårigheter.  Metod: Författarna genomförde en icke experimentell kvantitativ tvärsnittsstudie med vuxna individer som spelade datorspel minst 2h/dag. 116 svar inkluderades till frågeställning 1 (internt bortfall till frågeställning 2 & 3 n = 20). En webbenkät publicerades i tre svenska Facebook-grupper inriktade mot datorspel för att kartlägga deltagarnas sömn samt fysisk aktivitet. Sömnen mättes med Insomnia Severity Index (ISI) och den fysiska aktiviteten mättes med International Activity Questionnaire Short Form (IPAQ-SF). Resultat: 70% av studiens respondenter hade “Inga kliniska sömnsvårigheter” enligt ISI och 59% bedömdes ha en hög aktivitetsgrad enligt IPAQ-SF. Det förekom inget signifikant samband mellan respondenternas sömnbesvär och fysiska aktivitet.  Diskussion: Förekomsten av sömnbesvär och antal deltagare som uppfyllde kriterierna för insomni var jämförbar med den svenska populationen. Vidare var respondenternas aktivitetsgrad högre än vad som tidigare setts i den svenska befolkningen. För att kunna se ett tydligare samband mellan dessa faktorer är bedömningen att det skulle krävas ett större urval med respondenter. / Background: Computer games can negatively impact sleep in individuals who play more than 2 hours/day. Physical activity can improve many parts of sleep such as sleep quality and less daytime fatigue. The purpose of the study was to map the level of physical activity and sleep difficulties in computer-gaming adults, and to investigate whether there is a correlation between physical activity and sleep difficulties. Method: The authors conducted a non-experimental quantitative cross-sectional study with computer-gaming adults who played at least 2 hours/day. 116 answers were included to question 1 (internal dropout to question 2 & 3 n = 20). A web-survey was published in three Swedish computer game-oriented Facebook groups to map the participants' sleep and physical activity. Sleep was measured with the Insomnia Severity Index (ISI) and physical activity was measured with the International Activity Questionnaire Short Form (IPAQ-SF) Results: 70% of the study respondents had “No clinical sleep difficulties” according to ISI and 59% were classified to have a high activity level according to IPAQ-SF. There was no significant association between the respondents' sleep difficulties and physical activity. Discussion: The occurrence of sleep difficulties and the number of participants who met the criteria for insomnia was comparable to the Swedish population. Furthermore, the respondents' degree of physical activity was higher than previously seen in the Swedish population. In order to be able to see a clearer connection between these factors, the assessment is that a larger selection of respondents would be required.

Sick leave due to poor mental health has increased in Sweden and the need for more knowledge about possible work adaption is big. Under the right conditions telecommuting seems to have positive effects on mental health. Research shows that voluntariness is an important factor. The aim of this study was to investigate the relationship between self-reported symptoms of burnout, depression, sleeping problems and willingness to telecommute. The outcome was the amount of days a person wishes to telecommute. The sample consisted of 1383 white collar workers from private and public sector. Two linear regression analyzes were performed, one without and one with control variables. The result of this study showed no relationship between self-reported symptoms of burnout, depression, sleeping problems and willingness to telecommute. However, it showed a significant relationship between some of the control variables and the outcome. These were age, telecommuting experience, commuting time and the amount of telecommuting currently performed. Future studies should focus on including more people with higher levels of poor mental health, and also investigate the possibility of using telecommuting as work adaption for this group.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第21036号 / 人健博第52号 / 新制||人健||4(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 任 和子, 教授 三谷 章, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

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Senare års forskning visar på att obstruktivt sömnapnésyndrom, OSAS, är en både underdiagnostiserad och underbehandlad sjukdom. Detta beror delvis på att många personer med OSAS är omedvetna om sitt tillstånd. Sjukdomen innebär återkommande totala andningsuppehåll under sömn och en hypoxi som leder till en rad olika komplikationer, däribland hjärtkärlsjukdomar. Syftet med denna studie var att utreda vad som påverkar OSAS och vilken roll sjuksköterskan kan spela i vården av dessa patienter. Metoden som användes var en litteraturundersökning. Resultatet baseras på tio vetenskapliga artiklar som erhölls genom databaserna PUBMED samt SAMSÖK. Teman som utkristalliserades var sömnposition, kroppsvikt och tandstatus. Trots att behandlingen av OSAS till stor del bygger på medicinska åtgärder visar resultaten i denna litteraturundersökning att sjuksköterskor har en viktig funktion i både upptäckten av nya fall samt i behandlingen. Omvårdnadsåtgärder såsom information om förändrad sömnposition och viktnedgång har visat sig ha signifikant betydelse för obstruktiv andning. / Medical research in recent years has shown that Obstructive Sleep Apnea Syndrome, OSAS, is an affliction for which both diagnosis and treatment are often inadequate. In part, this is due to the fact that many people suffering from OSAS are not aware of the problem. The disease causes recurrent complete stops of breathing during sleep and hypoxia that may bring about various complications, for instance cardiovascular disorders. The purpose of this study, carried out as a literature survey, was to determine what factors affect OSAS and what role the nurse may play in the care of patients suffering from this disease. The survey of the literature by means of the data bases PUBMED and SAMSÖK yielded ten scientific articles showing that although various medical measures constitute the treatment of choice of OSAS the nurse plays an important role in the treatment and the diagnosis of new cases. Preventive care measures such as information about appropriate sleeping positions and reduction of weight have proven to be of significant value in the treatment of OSAS.

The prospective Ulm-SPATZ study was investigated to assess the role of child sleeping quality between 4 to 6 years of age in affecting a partner’s sleeping and relationship satisfaction within a couple. The study was conducted using a triadic approach in which the child was included in the Actor-Partner-Interdependence Model (APIM). Sleeping quality of the child was determined by using the German version of the children’s sleep habits questionnaire, sleeping features of the parents were assessed by using the Munich chronotype questionnaire, and the partner relationship assessment was performed by employing the German version of the parenting stress index questionnaire. In 211 German triads, we observed that sleeping characteristics and partner relationship scores at different child ages are consistent for both men and women. Higher and statistically significant sleep duration, time spent in bed, the midpoint of sleep, time getting out of bed, and sleep onset in women compared to men during the working days were observed. The APIM analyses showed a significant direct effect of child sleep quality on the partner relationship satisfaction. In women, a mediated effect of child sleep quality acted through sleep duration and time spent in bed on the partner relationship satisfaction score during both free and working days. In men, low child sleep quality was found to be associated with increased sleep onset during both free and working days. Child sleep quality influences relationship satisfaction mostly in mothers, likely because of their higher involvement in childcare during working days. Distress in the couple could be counteracted by a major involvement of the fathers in child management.

L’un des principaux défis de la thérapie génique est d’identifier un vecteur sûr capable d’assurer un transfert efficace et une expression soutenue d’un gène d’intérêt thérapeutique dans les cellules cibles. L’émergence de vecteurs plasmidiques de nouvelles générations a permis d’atteindre ces objectifs et de considérer la thérapie génique non virale comme une alternative prometteuse aux vecteurs viraux pour le traitement de maladies génétiques ou acquises. Appartenant à ces nouvelles générations, les dérivés du vecteur pFAR4 sont des miniplasmides dépourvus de gène de résistance à un antibiotique. Leur propagation dans les cellules d’Escherichia coli est basée sur la suppression d’une mutation non-sens de type ambre introduite dans un gène essentiel de la souche productrice, permettant ainsi d’éliminer les risques associés à l’utilisation de gène de résistance à un antibiotique tout en diminuant la taille du vecteur. Le but de cette thèse est d’étudier le potentiel de ces vecteurs dans deux contextes de thérapie génique non virale : Dans une première approche, le potentiel du vecteur pFAR4 a été évalué pour l’expression d’un gène thérapeutique dans le foie de souris. Pour ce faire, un dérivé de ce vecteur exprimant le gène Sgsh à partir d’un promoteur spécifique des hépatocytes et codant la protéine sulfamidase, protéine défectueuse chez les patients souffrant de la maladie de Sanfilippo de type A, a été administré par injection hydrodynamique à des souris. Nous avons montré que le vecteur pFAR4 promeut dans le foie une expression élevée et soutenue de la sulfamidase, qui décline rapidement lorsque le gène Sgsh est administré par un vecteur contenant un gène de résistance à la kanamycine. Dans le cadre de cette étude, il a été établi que le profil d’expression obtenu avec le vecteur pFAR4 n’est pas lié à son insertion dans le génome des hépatocytes mais résulte, de par sa taille réduite, d’une protection contre les phénomènes d’extinction de transgène couramment observés in vivo avec les vecteurs conventionnels. Dans une seconde approche, le vecteur pFAR4 a été combiné à la technologie Sleeping Beauty (SB), dont l’un des constituants majeurs est la transposase hyperactive SB100X qui promeut la transposition d’un transgène, en l’excisant du plasmide qui le porte et en l’insérant dans le génome des cellules hôtes. Cette combinaison a été étudiée in vitro dans des cellules HeLa, en utilisant un transposon contenant soit le gène de résistance à la néomycine soit le gène codant la protéine fluorescente Vénus. Nous avons ainsi montré que le plasmide pFAR4 constituait un vecteur efficace pour les composants du système SB et que la combinaison pFAR4/SB conduisait à un taux de transgénèse augmenté par rapport à une association avec des plasmides conventionnels. Cette efficacité élevée résulte d’un niveau de transfection et d’un taux d’excision augmentés, tous deux favorisés par la taille réduite du plasmide. La combinaison pFAR4/SB devrait prochainement être utilisée pour transférer le gène codant le facteur anti-angiogénique PEDF (Pigment Epithelium-Derived Factor) à des cellules primaires de l’épithélium pigmentaire de la rétine ou de l’iris dans deux essais cliniques (Phase I/II) de thérapie génique ex vivo pour le traitement de la dégénérescence maculaire liée à l’âge (DMLA). / One of the main challenges in gene therapy is to identify safe vectors that promote an efficient gene delivery and a sustained therapeutic transgene expression level in targeted cells. The development of novel plasmid vectors allowed to reach these objectives and to consider non-viral gene therapy approaches as attractive alternatives to treat genetic and acquired disorders. The pFAR4 vector is a novel antibiotic-free mini-plasmid. In Escherichia coli, its propagation is based on the suppression of an amber nonsense mutation introduced into an essential gene, thus eliminating safety concerns classically attributed to antibiotic resistance markers present on conventional plasmid DNA vectors and allowing a reduction in plasmid size. The aim of this work was to investigate the potential of pFAR4 as a gene vector in two different non-viral gene therapy approaches. In a first approach, the potential of the pFAR4 vector was assessed for the expression of a therapeutic gene in mouse liver. To this end, a pFAR4 derivative expressing the Sgsh gene from a liver-specific promoter and coding the sulfamidase, an enzyme deficient in patients suffering from the Sanfilippo A disease, was tail vein hydrodynamically injected into mouse liver. We showed that the pFAR4 derivative promoted a high and prolonged sulfamidase expression which rapidly declined when the same expression cassette was delivered by a conventional plasmid containing a kanamycin resistance marker. It was established that the superior expression profile obtained with the pFAR4 derivative did not result from its integration in host genome but seemed to benefit from protection against transcriptional silencing. In a second approach, the pFAR4 vector was combined to the Sleeping Beauty transposon system that mediates transgene integration into host genomes, after its excision from a plasmid donor by the hyperactive SB100X transposase, in order to obtain a long-term expression in dividing cells. This combination was studied in vitro, delivering either the neomycin resistance gene or the fluorescent Venus protein-encoding gene into HeLa cells. We showed that the combination pFAR4/SB led to an increased transgenesis rate in comparison to the association of SB with conventional plasmids. The pFAR4/SB combination seemed to benefit from an elevated transfection efficiency and a higher excision rate, resulting from the reduced size of the pFAR4 vector. The two technologies should be soon used for the delivery of the anti-angiogenic pigment epithelium-derived factor (PEDF) gene into autologous primary pigment epithelial cells, in the context of two PhaseI/II clinical trials based on an ex vivo gene therapeutic approach for the treatment of neovascular age-related macular degeneration (nAMD).

The multi-armed bandit (MAB) problem provides a convenient abstraction for many online decision problems arising in modern applications including Internet display advertising, crowdsourcing, online procurement, smart grids, etc. Several variants of the MAB problem have been proposed to extend the basic model to a variety of practical and general settings. The sleeping multi-armed bandit (SMAB) problem is one such variant where the set of available arms varies with time. This study is focused on analyzing the efficacy of the Thompson Sampling algorithm for solving the SMAB problem. Any algorithm for the classical MAB problem is expected to choose one of K available arms (actions) in each of T consecutive rounds. Each choice of an arm generates a stochastic reward from an unknown but fixed distribution. The goal of the algorithm is to maximize the expected sum of rewards over the T rounds (or equivalently minimize the expected total regret), relative to the best fixed action in hindsight. In many real-world settings, however, not all arms may be available in any given round. For example, in Internet display advertising, some advertisers might choose to stay away from the auction due to budget constraints; in crowdsourcing, some workers may not be available at a given time due to timezone difference, etc. Such situations give rise to the sleeping MAB abstraction. In the literature, several upper confidence bound (UCB)-based approaches have been proposed and investigated for the SMAB problem. Our contribution is to investigate the efficacy of a Thomp-son Sampling-based approach. Our key finding is to establish a logarithmic regret bound, which non-trivially generalizes a similar bound known for this approach in the classical MAB setting. Our bound also matches (up to constants) the best-known lower bound for the SMAB problem. Furthermore, we show via detailed simulations, that the Thompson Sampling approach in fact outperforms the known algorithms for the SMAB problem.

Increased motivation by utilizing gamification is investigated in this report. Two problems in society were alerted by a finance company in collaboration with a Swedish university. The first problem was that people did not save enough for their retirement. The second problem was that some people saved money but did not have the money invested, which the finance company calls sleeping money. The company found that the reason for this was due to lack of motivation. In a general perspective, the two core problems are lack of motivation and unused resources in society. If sleeping resources were utilized, it could benefit those using the resource, the owner of the resource, and in society as a result of increased utilization of these resources. Multi-sided platforms are being used in various industries and are a great way to interconnect two different sides of a market, i.e. buyers and sellers. Gamification is proven to be an efficient way to motivate people. Therefore, the purpose of this study is to find a solution to how sleeping resources can be activated by utilizing gamification on a multi-sided platform. Generally, it was concluded that gamification can both intrinsically and extrinsically motivate users to activate sleeping resources. / Ökad motivation genom att använda spelifiering undersöks i denna rapport. Ett finansbolag i samarbete med ett svenskt universitet uppmärksammade två problem i samhället. Det första problemet var att människor inte sparade tillräckligt för sin pension. Det andra problemet var att vissa människor sparade pengar men inte hade pengarna investerade, vilket finansbolaget kallar sleeping money eller på svenska: sovande pengar. Företaget kom fram till att orsaken till detta berodde på brist av motivation. I ett generellt perspektiv är de två kärnproblemen brist på motivation och att det finns mycket outnyttjade resurser i samhället. Om de outnyttjade resurserna används kan det gynna de som använder resursen, ägaren av resursen och hela samhället som ett resultat av ökat utnyttjande av dessa resurser. Flersidiga plattformar används i olika branscher och är ett bra sätt att koppla samman två olika sidor på en marknad, det vill säga köpare och säljare. Spelifiering har visat sig vara ett effektivt sätt att motivera människor. Syftet med denna studie är därför att hitta en lösning på hur sovande resurser kan aktiveras genom att använda spelifiering på en flersidig plattform. Generellt drogs slutsatsen att spelifiering kan aktivera sovande resurser med både inre och yttre motivation.

Sleeping Beauty (SB) Transposon-basierte Vektoren werden als Alternative zu viralen Vektoren für T-Zell-Gentherapie erforscht und ermöglichen eine schnelle und kostengünstige Genmanipulation von T-Zellen. Die Verwendung von Transposon-Vektoren erfordert jedoch die DNA-Elektroporation von T-Zellen, die sich schädlich auf T-Zellen auswirkt. DNA-elektroporierte T-Zellen weisen eine verringerte Lebensfähigkeit und eine verzögerte Aktivierung nach Stimulation des T-Zell-Rezeptors (TCR) auf. Um die Nachteile der Transposon-basierten T-Zell-Genmanipulation zu überwinden, haben wir neuartige SB-Vektoren entwickelt. Durch die Kombination von SB Transposon-basierten Minicircle-Vektoren mit SB100X Transposase-mRNA konnten T-Zellen effizient genmodifiziert werden. Unser Ansatz reduzierte die T-Zell-Mortalität und steigerte gleichzeitig die Transfektionseffizienz. Mit diesen neuartigen Vektoren wurde die stabile Expression verschiedener TCRs und CARs in über 50% der eingesetzten T-Zellen erreicht. Gentechnisch manipulierte T-Zellen konnten Antigen-spezifisch stimuliert werden und zeigten effiziente Zytokin-Sekretion und Tumorzell-Lyse. Weiterhin haben wir miRNAs entwickelt, die die Expression der endogenen TCR-Ketten unterdrücken. Der Einbau dieser miRNAs in die TCR-Expressionskassette erhöhte die Oberflächenexpression des therapeutischen TCRs, verringerte die Fehlpaarung mit endogenen TCR-Ketten und erhöhte die T-Zell-Funktionalität. Ein direkter Vergleich von SB- und Virus-modifizierten T-Zellen zeigte sowohl in vitro als auch in vivo eine vergleichbare Wirksamkeit der modifizierten T-Zellen hinsichtlich Zytokin-Sekretion, Tumorzell-Lyse und Tumorkontrolle. In dieser Arbeit konnte gezeigt werden, dass SB Minicircle-Vektoren die Herstellung von genetisch modifizierten T-Zellen ermöglichen und diese Tumor-spezifische Wirksamkeit aufweisen. Dieser Ansatz könnte die Herstellung therapeutischer T-Zellen für die personalisierte T-Zell-Gentherapie vereinfachen und beschleunigen. / Sleeping Beauty (SB) transposon-based vectors have entered clinical trials as an alternative to viral vectors for T cell gene therapy, offering time- and cost-efficient engineering of therapeutic T cells. However, transposon vectors require DNA electroporation into T cells, which we found to cause adverse effects. T cell viability was decreased, and DNA-transfected T cells showed delayed activation upon T cell receptor (TCR) stimulation regarding blast formation and proliferation. To overcome the limitations of transposon-based T cell engineering, we investigated the effect of DNA electroporation on T cells and developed novel SB vectors. T cells could efficiently be engineered with Sleeping Beauty vectors by combining SB transposon minicircles and SB100X transposase mRNA. Our approach reduced T cell mortality and substantially enhanced transfection efficiency. We achieved stable expression of several TCRs and CARs in more than 50% of the transfected T cells compared to 15% when conventional plasmids were used. T cells engineered to express a tumor-specific TCR mediated effective tumor cell lysis and cytokine secretion upon antigen-specific stimulation. Furthermore, we developed miRNAs to silence the expression of the endogenous TCR chains. Incorporation of these miRNAs into the TCR expression cassette increased surface expression of the therapeutic TCR, diminished mispairing with endogenous TCR chains, and enhanced T cell functionality. Importantly, a direct comparison of SB minicircle- and RV-engineered T cells in vitro as well as in vivo demonstrated equal T cell efficacy with regards to cytokine release, tumor cell lysis and tumor control. We demonstrated that SB minicircles enable the generation of gene-modified T cells with tumor-specific reactivity. Our approach facilitates the manufacturing of therapeutic T cells with superior biosafety and accelerates the generation of patient-specific T cell products for personalized T cell gene therapy.