No / Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome. Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project. Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

No / After more than 3500 years of occupation in the Neolithic and Bronze Age, the many lake-dwellings’ around the Circum-Alpine region ‘suddenly’ came to an end. Throughout that period alternating phases of occupation and abandonment illustrate how resilient lacustrine populations were against change: cultural/environmental factors might have forced them to relocate temporarily, but they always returned to the lakes. So why were the lake-dwellings finally abandoned and what exactly happened towards the end of the Late Bronze Age that made the lake-dwellers change their way of life so drastically? The new research presented here draws upon the results of a four-year-long project dedicated to shedding light on this intriguing conundrum. Placing a particular emphasis upon the Bronze Age, a multidisciplinary team of researchers has studied the lake-dwelling phenomenon inside out, leaving no stones unturned, enabling identification of all possible interactive socio-economic and environmental factors that can be subsequently tested against each other to prove (or disprove) their validity. By re-fitting the various pieces of the jigsaw a plausible, but also rather unexpected, picture emerges.

京都大学 / 新制・課程博士 / 博士(農学) / 甲第25315号 / 農博第2581号 / 京都大学大学院農学研究科農学専攻 / (主査)教授 白岩 立彦, 教授 那須田 周平, 教授 田中 千尋 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

Structural Health Monitoring (SHM) is the implementation of damage detection and characterization algorithms using in vitro sensing and actuation for rapidly determining faults in structural systems before the damage leads to catastrophic failure. SHM systems provide near real time information on the state of the integrity of civil, mechanical and aerospace structures. A roadblock in implementing SHM systems in practice is the possibility of false positives introduced by environmental changes. In particular, temperature changes can cause many SHM algorithms to indicate damage when no damage exists. While several experimentally based efforts have been attempted to alleviate temperature effects on SHM algorithms, fundamental research on the effects of temperature on SHM has not been investigated. The work presented in this dissertation composes of two main parts: the first part focuses on the experimental studies of different mechanical structures of aluminum beams, lug samples and railroad switch bolts. The experimental study of the aluminum lug samples and beams is done to propose and examine methods and models for in situ interrogation and detection of damage (in the form of a fatigue crack) in these specimen and to quantify the smallest detectable crack size in aluminum structures. This is done by applying the electrical impedance-based SHM method and using piezoceramic sensors and actuators. Moreover, in order to better extract the damage features from the measured electrical impedance, the ARX non-linear feature extraction is employed. This non-linear feature extraction, compared to the linear one, results in detection of damages in the micro-level size and improves the early detection of fatigue cracks in structures. Experimental results also show that the temperature variation is an important factor in the structural health monitoring applications and its effect on the impedance-based monitoring of the initiation and growth of fatigue cracks in the lug samples is experimentally investigated. The electrical impedance-based SHM technique is also applied in monitoring the loosening of bolted joints in a full-scale railroad switch and the sensitivity of this technique to different levels of loosening of the bolts is investigated. The second part of the work presented here focuses on the analytical study and better understanding of the effect of temperature on the vibration-based SHM. This is done by analytical modeling of the vibratory response of an Euler-Bernoulli beam with two different support conditions of simply supported and clamped-clamped and with a single, non-breathing fatigue crack at different locations along the length of the beam. The effect of temperature variations on the vibratory response of the beam structure is modeled by considering the two effects of temperature-dependent material properties and thermal stress formations inside the structure. The inclusion of thermal effects from both of these points of view (i.e. material properties variations and generation of thermal stresses) as independent factors is investigated and justified by studying the formulations of Helmholtz free energy and stresses inside a body. The effect of temperature variations on the vibratory response of the cracked beam are then studied by integrating these two temperature-related effects into the analytical modeling. The effect of a growing fatigue crack as well as temperature variations and thermal loadings is then numerically studied on the deflection of the beam and the output voltage of a surface-bonded piezoceramic sensor. / Ph. D.

SAMMANFATTNING Bakgrund: Fysisk aktivitet främjar hälsan och medför positiva effekter för kroppen. Barns och ungdomars fysiska aktivitet påverkas av olika faktorer på individ- och omgivningsnivå. Faktorerna interagerar med varandra och påverkar den fysiska aktiviteten på olika sätt och i varierande grad, faktorerna kan delas in i olika system i den Ekologiska systemteorin. Det kan exempelvis handla om föräldrars och vänners attityder och hur den fysiska miljön är utformad. Syfte: Syftet med denna studie var att utifrån ett Ekologiskt systemteoretiskt perspektiv undersöka 20-åringars upplevelse av vilka faktorer som har haft betydelse för hur fysiskt aktiva de har varit från 11-års ålder fram till idag. Metod: Studien genomfördes med en kvalitativ design med induktiv ansats. Fem deltagare intervjuades utifrån en intervjuguide innehållande semistrukturerade frågor. Kvalitativ innehållsanalys användes för att analysera och tolka materialet. Resultat: Analysen resulterade i 4 kategorier med 14 underkategorier. Kategorierna blev: ”Engagemang i idrotten påverkas av inre känslor och yttre krav”, ”Att vara en del av gemenskapen”, ”Den fysiska miljön och de socioekonomiska förutsättningarnas inverkan” och ”Andra möjliga påverkande faktorer på utövande”. Slutsats: Resultatet visade att de faktorer som har störst påverkan finns inom micro- och exosystemen. Faktorerna varierar med åldern och innefattar främst föräldrar, vänner och tillgänglighet. / ABSTRACT Background: Physical activity promotes health, and will have positive effects for the body. Children and adolescents physical activity is influenced by different factors at individual and environmental level. The factors integrate with each other and affect the physical activity in different ways and can be divided into different systems according to the ecological systems theory. It could for example involve the attitudes of parents and friends and how the physical environment is designed. Aim: Based on Ecological systems theory the purpose of this study is to examine 20-yearolds experience of which factors that have had an impact on their physical activity from 11 years old until today. Method: The study was conducted with a qualitative design with inductive approach. Five participants were interviewed based on an interview guide containing semi-structured questions. Qualitative content analysis was used to analyze and interpret the material. Result: The analysis resulted in 4 categories with 14 subcategories. The categories were: "Involvement in sport is affected by internal feelings and external demands", "Being a part of the community", "The impact of physical environment and socioeconomic conditions" and "Other possible factors affecting the activity". Conclusion: The result showed that the factors with the greatest impact is within the micro and exosystems. The factors varies over time and focuses on parents, friends and availability.

Meningsfulla aktiviteter ingår i arbetsterapeutens kompetens och något som arbetsterapeuter bör grunda sina interventioner i. Syftet med examensarbetet var att beskriva upplevelse av möjlighet och hinder till meningsfulla aktiviteter hos äldre med hemtjänst i ordinärt boende. Examensarbetet hade en kvalitativ design med semistrukturerade intervjuer. Tio deltagare intervjuades. En kvalitativ innehålls-analys resulterade i faktorer som både möjliggjorde och hindrade meningsfulla aktiviteter. Tre kategorier identifierades; ”Den fysiska miljöns betydelse”, miljön kring den äldre påverkade utförandet beroende på om den var anpassad eller inte, om man hade närhet till aktivitet, om man hade möjlighet till transport samt att den varma årstiden möjliggjorde. ”Hindrande Personfaktorer”, kroppsliga begränsningar och mentala begränsningar påverkade möjlighet till utförande av meningsfulla aktiviteter. ”Organiserade sociala aktiviteter”, kyrkan möjliggjorde aktivitet, hemtjänsten stöttar till viss del och organiserade aktiviteter har lagts ned. Temat ”Det handlar inte om hur gammal man är, utan hur man är gammal” framkom. Samhällets syn på äldre samt äldres internaliserade syn på sig själva påverkar möjlighet till utförande av meningsfulla aktiviteter. Slutsatsen var att möjlighet till meningsfulla aktiviteter påverkas av omgivningsfaktorer och personfaktorer. Denna kunskap bidrar till att arbetsterapeuter kan arbeta för att äldre ska kunna utföra meningsfulla aktiviteter genom att uppmärksamma de hinder och möjligheter som den äldre upplever. / Meaningful occupations are part of the occupational therapist’s competence and should be the foundation in interventions. The aim was to describe the experience of the possibilities and hindrance to meaningful activities for elderly in ordinary living who has support from home care. The thesis had a qualitative design with semi structured interviews with ten participants. The result showed factors that enabled and disabled the possibility to perform meaningful activities. “The importance of the physical environment”, the environment around the elderly affected the performance due to if it was adapted or not. Activities nearby, transportation as well as light and warmth enabled meaningful activities. “Obstructive personal factors”, physical body factors and mental body factors affected the ability to perform meaningful activities. “Organized social activities”, the church enabled activities, the home care support to some extent and organizations have cancelled activities. The theme “It´s not about how old you are, but how you are old” emerged. Society’s opinion about the elderly and elder’s internalised opinion about themselves affect the possibility to meaningful activities. The conclusion showed that environmental factors and individual factors affected the ability to perform meaningful activities. This knowledge contributes to occupational therapists work to enable meaningful activities for the elderly.

Future climate scenarios in the Baltic Sea project increasing sea surface temperature, as well as increasing precipitation and river runoff resulting in decreased salinity. These changes can severely impact the dynamics and function of brackish water communities, specifically phytoplankton. Phytoplankton are a significant source of organic matter to other trophic levels, and some species can be toxic. Their response to future climate conditions is of great relevance for the health of humans and aquatic ecosystems. The aim of this thesis was to assess the potential for climate-induced changes, such as decreasing salinity, to affect phytoplankton dynamics, physiology and chemical profiles in the Baltic Sea.      Phytoplankton successional patterns in the Baltic Proper consist of a spring bloom where diatoms and dinoflagellates co-occur and a summer bloom dominated by filamentous/colonial cyanobacteria. The consensus is that future warmer conditions will promote filamentous/colonial cyanobacteria blooms. This thesis shows that phytoplankton biomass in the spring bloom was lower in years with milder winters compared with cold winters. This suggests that in terms of annual carbon export to higher trophic levels, loss of biomass from the spring bloom is unlikely to be compensated by summer cyanobacteria. High frequency sampling of phytoplankton performed in this thesis revealed a strong relationship between the dynamics of pico- and filamentous cyanobacteria. Large genetic diversity was found in cyanobacterial populations with high niche differentiation among the same species. At community level, high temperature and low salinity were the main factors shaping the summer cyanobacterial composition. These conditions may promote the predominance of opportunistic filamentous cyanobacteria, e.g. Nodularia spumigena. This species produces various bioactive compounds, including non-ribosomal peptides such as the hepatotoxin nodularin. In this work, N. spumigena subpopulations evolved different physiological strategies, including chemical profiles, to cope with salinity stress. This high phenotypic plasticity ensures survival in future climate conditions. Under salinity stress, some subpopulations displayed shorter filaments as a trade-off. This indicates that the future freshening of the Baltic Sea may promote grazing on filamentous cyanobacteria and modify carbon flows in the ecosystem. In this thesis, Baltic N. spumigena chemotypes and genotypes grouped into two main clusters without influence of geographical origin. Thus, chemical profiling can be used to explore conspecific diversity in closely genetically related N. spumigena subpopulations.      Overall, this thesis has significantly expanded the knowledge on phytoplankton community and population responses to short- and long-term environmental changes, relevant to project the impacts of future climate conditions in the Baltic Sea.

Studies performed on natural pathosystems revealed that the spatial structure of the metapopulation plays an important role in the development and spread of disease; phytopathological experimental studies have also revealed a significant effect of climatic factors on the presence of the disease (incidence) and the level of infection (prevalence) in populations. The aim of this study was to explore a natural pathosystem from both sides at the same time and to see which local and spatial environmental factors influence the development of pathosystem. Study focuses on population biology of natural pathosystem Podospaera balsaminae - Impatiens noli-tangere, which has not been investigated yet. In the study area (between the city Sázava (Benešov district) and village Vlkančice) host populations occurred in 78 (64 of them were infected) in 2013 and 82 populations (61 of them were infected) in 2014. Size of host populations had the strongest effect to incidence and prevalence of disease in the pathosystem. In larger populations, the disease occurred more often, developed faster and was higher. The rate of spread of the pathogen territory and the rate of population host connectivity had also strong effect. The abundance of pathogen in the studied area and the level of connectivity of host populations also...

Autism is a complex disorder with possible genetic, epigenetic and environmental components. As the etiology remains uncertain and an increase in incidence is suspected, the involvement of possible environmental risk factors has gained increasing attention. With this thesis, I aim to provide tools for assessing such risk factors. Firstly, I aim to construct a questionnaire for the analysis of an environmental component in the etiology of autism. Secondly, I aim to assess the importance of prenatal exposure to metals in certain diseases and thirdly I aim to construct a methodology enabling the analysis of the mitochondrial epigenome, which is especially interesting in relation to autism as mitochondrial diseases occur more frequently in an autistic population than in the general population. For the creation of the questionnaire the scientific literature was reviewed. The resulting questionnaire contains general, prenatal, neonatal and paternal risk factors. The metal analysis was conducted on the cord blood of patients who later developed autism, antinuclear antibodies positive rheumatoid arthritis or diabetes, which were then compared to healthy control subjects. My findings propose a link between elevated levels of cord blood cadmium or aluminum and rheumatic arthritis. In addition, elevated aluminum levels might be associated with autism. In regards to the analysis of the mitochondrial epigenome, to my knowledge, no standard protocol exists with frozen human whole blood as a source. In this thesis, I succeeded in creating the basis for such a protocol, however still needing several small modifications for an increased overall yield.

Student Number : 0310496H - MPH research report - Faculty of Health Sciences / This study compares pharmaceutical company research on new medicines in South Africa with the country’s burden of disease and describes the process and criteria that companies use to set their research priorities. A quantitative survey of pharmaceutical companies shows that company research conducted from 2000 to 2003 is moderately associated with the country’s burden of disease estimates for 2000. The degree of association is dependent on which measures of company research and burden of disease are compared, and which comparative statistic is used. A qualitative analysis of company interviews reveals that feasibility of clinical trials, market forces, and environmental factors are core criteria for company research priority setting. The burden of disease, although important, is not a sole criterion, and has considerable limitations. Furthermore, this study reveals the complex nature of health priority setting by pharmaceutical companies and thus can assist policy decision makers in identifying practical strategies to encourage research in diseases of need by pharmaceutical companies.