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Coming dissertations at Uppsala university

  • Antibiotic resistance gone wild : A One Health perspective on carriage, selection and transmission of Extended-Spectrum Cephalosporinase- and Carbapenemase-producing Enterobacteriaceae Author: Clara Atterby Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-397218 Publication date: 2019-12-18 13:34

    Antibiotics have saved millions of lives since they came into clinical use during the Second World War in the 1940s. Today, our effective use of antibiotics is under great threat due to emerging antibiotic resistance in bacteria. This thesis addresses the problems of antibiotic resistance from a ”One Health” perspective. The focus is on antibiotic resistant Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) in the environment and wildlife, and also considering the situation in healthy humans and livestock. 

    In Paper I-III, high occurrence of Extended-Spectrum Beta-Lactamase (ESBL) -producing E. coli and/or K. pneumoniae was detected in fecal samples from wild birds, and the bacteria had genetic similarities to bacteria that cause disease in humans. Proximity to humans was associated with higher occurrence of cephalosporinase (ESBL and pAmpC)-producing E. coli in wild gulls. In Paper IV, ciprofloxacin resistant E. coli was enriched in the gut of mallards exposed to low concentrations of ciprofloxacin, and plasmid conjugation between E. coli bacteria readily took place. In Paper V, carbapenem resistant and blaOXA-48 harbouring- E. coli/K. pneumoniae was rare, but present in healthy humans in rural Cambodia, while cephalosporinase-producing E. coli/K. pneumoniae was common in both humans and livestock. The same ESBL/pAmpC genes were detected in humans and livestock, and exposure to animal manure and slaughter products were risk factors for fecal carriage in humans.

    In conclusion, wild birds can function as potential resistance reservoirs and sentinels for antibiotic resistant E. coli. Environmental pollution from humans is the primary source for antibiotic resistant Enterobacteriaceae found in wildlife, but selection for antibiotic resistant bacteria may also occur in wild birds. The results indicate that transmission of cephalosporinase-producing E. coli/K. pneumoniae occur between wildlife, humans and livestock, but more in-depth molecular work is needed to determine the mechanisms of dissemination. The high community carriage of multidrug-resistant bacteria in rural Cambodia is worrying and highlights Southeast Asia as a hotspot for antibiotic resistance. Antibiotic resistance surveillance is biased towards high-income countries and research should be focused more on low- and middle-income countries, and also include the important “One Health” perspective.

  • Interface Studies for Gold-based Electrochemical DNA Sensors Author: Xingxing Xu Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-397807 Publication date: 2019-12-18 12:57

    Gold based label-free electrochemical DNA sensors have been widely studied for biomarker diagnostics. The sensitivity and reproducibility of these sensors are determined by the sensing interface: the DNA modified gold surfaces. This thesis systematically studies the preparation processes of the DNA sensor interfaces as well as their effects on the sensor performance. First, three pretreatment methods to clean the gold electrode surface and their influence on the subsequent binding of thiolated molecules were carefully investigated. As we found that the surface pretreatment method involving cyclic voltammetry (CV) in H2SO4 may induce structural changes to the gold surface, thus greatly impacting the thiolated molecule binding, the factors influencing this pretreatment method were studied. Practical guidelines were summarized for preparing a clean and reproducible gold surface prior to functionalization. Afterwards, the effects of the surface coverage density of probe DNA and the salt concentration on the probe-target DNA hybridization on a gold sensing surface were systematically investigated using surface plasmon resonance (SPR) analysis. Based on the SPR results, the maximum potentiometric signal that could be generated by the DNA hybridization on the surface, and the detection limits, were estimated for different experimental conditions. These estimations were further compared with experimental results obtained using silicon nanowire field effect transistors (SiNW FET) with DNA modified gold on the gate oxide. Practical limitations for the potentiometric DNA sensor were analysed and discussed. Finally, the stability and reproducibility issues on the electrochemical impedance spectroscopy (EIS) analyses of DNA hybridization were also studied on the aptamer/mercaptohexanol (MCH)-modified gold surface. The root cause for the drift problems in this type of sensor and the temperature effects on the aptamer/MCH modified surface were identified. This thesis could serve as a practical reference for the preparation and understanding of the sensing interface of gold-based electrochemical DNA sensors.

  • Changing Swedish sickness insurance : Policies, institutions and outcomes Author: Nadja Grees Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-397628 Publication date: 2019-12-18 12:42

    The aim of this thesis is to contribute to welfare state theorising by analysing changing risk protection in Swedish sickness insurance and demonstrate how the understanding of such, and its implications, can be enhanced by strategic methodological choices. When analysing formal policy change in the compulsory sickness insurance system, it is concluded that the Swedish system fulfils almost every aspect of a so called social democratic welfare state, and no institutional shift can be discerned over time. When instead studying the interaction between compulsory and occupational benefits, and when investigating differences between diverse groups on the labour market and changes over time, it is demonstrated that there has been an institutional shift in the Swedish system. The balance in regulation between state and collective agreements has moved substantially in the direction of the latter. In terms of the basis for entitlements, a shift from citizenship/residence and labour force participation towards occupational categories has occurred. Considering the replacement levels of the public system, there has also been a shift towards inadequate benefits due to a low ceiling. Such findings emphasise the importance of including occupational systems, and of not treating the population as a homogenous mass, when studying risk protection. When focusing the analysis on how a system functions in practice rather than in theory as is usually done, and thus focusing on non-take-up of occupational benefits, it is shown that a large group of individuals are missing out on the benefit to which they have a right due to their occupational category. Such a fact has implications in terms of risk protection. The most obvious implication of high levels of non-take-up of occupational insurance is reduced individual income security for the affected groups. As the non-take-up is unevenly distributed among groups, such results also indicate that the traditional stratification in the system is strengthened but also that new groups of individuals are worse off than others, thus causing a new basis for stratification within the system.

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