| 1. |
- Fang, Xin, et al.
(författare)
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Comparison of Frequentist and Bayesian Generalized Additive Models for Assessing the Association between Daily Exposure to Fine Particles and Respiratory Mortality : A Simulation Study
- 2019
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Ingår i: International Journal of Environmental Research and Public Health. - Basel, Switzerland : MDPI. - 1661-7827 .- 1660-4601. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the performance of frequentist and Bayesian generalized additive models (GAMs) in terms of accuracy and precision for assessing the association between daily exposure to fine particles and respiratory mortality using simulated data based on a real time-series study.Methods: In our study, we examined the estimates from a fully Bayesian GAM using simulated data based on a genuine time-series study on fine particles with a diameter of 2.5 m or less (PM2.5) and respiratory deaths conducted in Shanghai, China. The simulation was performed by multiplying the observed daily death with a random error. The underlying priors for Bayesian analysis are estimated using the real world time-series data. We also examined the sensitivity of Bayesian GAM to the choice of priors and to true parameter.Results: The frequentist GAM and Bayesian GAM show similar means and variances of the estimates of the parameters of interest. However, the estimates from Bayesian GAM show relatively more fluctuation, which to some extent reflects the uncertainty inherent in Bayesian estimation.Conclusions: Although computationally intensive, Bayesian GAM would be a better solution to avoid potentially over-confident inferences. With the increasing computing power of computers and statistical packages available, fully Bayesian methods for decision making may become more widely applied in the future.
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| 2. |
- Ruoqing, Chen, 1985-
(författare)
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Parental cancer and children’s well-being : understanding the potential role of psychological stress
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Early life stress has a major influence on one’s health through the life course. During childhood, early experience may not only affect the normal brain development, but also influence the susceptibility to mental and physical disorders. A cancer diagnosis in a parent may cause substantial distress in the children, who may have to confront and adapt to short- and long-term changes in their lives and subsequently experience a higher risk of physical and psychosocial problems. Therefore, the first aim of this thesis was to examine whether parental cancer is associated with physical and mental health problems in the affected children using data from the Swedish national registers. Further, to explore the potential mechanism determining the impact of stress on children’ health, we focused on the brain development in childhood and investigated the association between stress biomarkers and brain morphology, using data from a Dutch population-based cohort.In Study I, we assessed the association between parental cancer and risk of injury in a large representative sample of Swedish children. We found that parental cancer was associated with a higher risk of hospital contacts for injury, particularly during the first year after the cancer diagnosis and when the parent experienced a psychiatric illness after the cancer diagnosis. The risk increment reduced during the second and third years and became null afterwards.Given the observed higher risk of adverse physical health in terms of injury, we further investigated the influence of parental cancer on adverse mental health in terms of psychiatric disorders among children. In Study II, we constructed a matched cohort, and separately examined the associations between parental cancer diagnosed during pregnancy or after birth and clinical diagnoses of psychiatric disorders or use of prescribed psychiatric medications. Paternal but not maternal cancer during pregnancy appeared to be associated with a higher risk of psychiatric disorders, primary among girls. Parental cancer after birth conferred a higher risk of clinical diagnoses of psychiatric disorders, particularly stress reaction and adjustment disorders. The affected children also experienced a higher risk of use of prescribed psychiatric medications, particularly anxiolytics. The latter associations were most pronounced for parental cancer with poor expected survival and for parental death after cancer diagnosis.In Study III, we focused on other domains of mental and physical health affected by parental cancer. We examined the associations of parental cancer with intellectual performance, stress resilience, and physical fitness among boys that underwent the compulsory military conscription examination during early adulthood. We observed positive associations of parental cancer with low stress resilience and low physical fitness, with stronger associations noted for parental cancer with poor expected survival and for a loss of parent through death after cancer diagnosis. No overall association was observed between parental cancer and intellectual performance, but the parental cancer with poor expected survival or resulting in a death of the parent was associated with a higher risk of low intellectual performance.
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| 3. |
- Bian, Xiaolei, 1990-
(författare)
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State Estimation of Lithium-ion Batteries
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To guarantee the safety operation, the key states of lithium-ion battery, e.g., the state of charge and the state of health, must be estimated and monitored accurately. This thesis is mainly to develop models and algorithms to accurately and robustly estimate the key battery states, based on the available measurements i.e., current and voltage. All the work is based on four published papers and can be divided into three parts.The first part of this work presents a two-step parameter optimization method for online state of charge estimation of lithium-ion battery. The particle swarm optimization is exploited for model parametrization and extended Kalman filter tuning. Within this particle swarm optimization-based framework, the searching boundary is derived by scrutinizing the error transition property of the test system, which can narrow the searching region and increase the computational efficiency. In general, the proposed method can well exploit the potential of model-based estimators, leading to a robust model compatibility and optimized performance.In the second part of this thesis, two novel models are developed to estimate the state of health of lithium-ion battery. The first one is an open circuit voltage-based model, which describes the open circuit voltage as a function of the state of charge by a polynomial, with a lumped thermal model to account for the effect of temperature. It requires a prior learning from the initial constant-current profile. The second model is an incremental capacity analysis-based model, which defines the dependence of the state of charge on the open circuit voltage using a capacity model. It can be learning-free, with the parameters subject to certain constraints. Both models use an equivalent circuit model to characterize the constant-current profiles and a nonlinear least squares method to identify the involving parameters. These two models are validated by aging experiments, and the results show that both can give accurate state-of-health estimation.The third part of the thesis introduces a fusion-type state-of-health estimator by combining the model-based profile reconstruction and the incremental capacity analysis-based state estimation. The above-mentioned open circuit voltage-based model is employed here to mitigate the noise-induced unfavorable numerical conditions and to modify the incremental capacity curves. Leveraging the modified incremental capacity curves, a set of feature-of-interests are extracted and evaluated, and several cautiously selected ones are used to estimate the state of health of lithium-ion battery. Long-term cycling tests on different lithium-ion batteries are used for validation. This fusion-type method has comparable accuracy and better robustness, compared with the model-based methods. Moreover, the proposed estimator has a good generality to different batteries and also promises an excellent robustness against cell inconsistency, noise corruption, temperature variety, and profile partialness.
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| 4. |
- Dragisic, Zlatan, 1987-
(författare)
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Completion of Ontologies and Ontology Networks
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The World Wide Web contains large amounts of data, and in most cases this data has no explicit structure. The lack of structure makes it difficult for automated agents to understand and use such data. A step towards a more structured World Wide Web is the Semantic Web, which aims at introducing semantics to data on the World Wide Web. One of the key technologies in this endeavour are ontologies, which provide a means for modeling a domain of interest and are used for search and integration of data.In recent years many ontologies have been developed. To be able to use multiple ontologies it is necessary to align them, i.e., find inter-ontology relationships. However, developing and aligning ontologies is not an easy task and it is often the case that ontologies and their alignments are incorrect and incomplete. This can be a problem for semantically-enabled applications. Incorrect and incomplete ontologies and alignments directly influence the quality of the results of such applications, as wrong results can be returned and correct results can be missed. This thesis focuses on the problem of completing ontologies and ontology networks.The contributions of the thesis are threefold. First, we address the issue of completing the is-a structure and alignment in ontologies and ontology networks. We have formalized the problem of completing the is-a structure in ontologies as an abductive reasoning problem and developed algorithms as well as systems for dealing with the problem. With respect to the completion of alignments, we have studied system performance in the Ontology Alignment Evaluation Initiative, a yearly evaluation campaign for ontology alignment systems. We have also addressed the scalability of ontology matching, which is one of the current challenges, by developing an approach for reducing the search space when generating the alignment.Second, high quality completion requires user involvement. As users' time and effort are a limited resource we address the issue of limiting and facilitating user interaction in the completion process. We have conducted a broad study of state-of-the-art ontology alignment systems and identified different issues related to the process. We have also conducted experiments to assess the impact of user errors in the completion process.While the completion of ontologies and ontology networks can be done at any point in the life-cycle of ontologies and ontology networks, some of the issues can be addressed already in the development phase. The third contribution of the thesis addresses this by introducing ontology completion and ontology alignment into an existing ontology development methodology.
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| 5. |
- Engberg, David
(författare)
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Atom Probe Tomography of TiSiN Thin Films
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the wear resistant coating TiSiN and the development of the analysis technique atom probe tomography (APT) applied to this materials system. The technique delivers compositional information through time-of-flight mass spectrometry, with sub-nanometer precision in 3D for a small volume of the sample. It is thus a powerful technique for imaging the local distribution of elements in micro and nanostructures. To gain the full benefits of the technique for the materials system in question, I have developed a method that combines APT with isotopic substitution, here demonstrated by substitution of natN with 15N. This alters the time-of-flight of ions with of one or more N and will thereby enable the differentiation of the otherwise inseparable isotopes 14N and 28Si. Signs of small-scale fluctuations in the data led the development of an algorithm needed to properly visualize these fluctuations. A method to identify the best sampling parameter for visualization of small-scale compositional fluctuations was added to an algorithm originally designed to find the best sampling parameters for measuring and visualizing strong compositional variations. With the identified sampling parameters, the nano-scale compositional fluctuations of Si in the metal/metalloid sub-lattice could be visualized. The existence and size of these fluctuations were corroborated by radial distribution functions, a technique independent of the previously determined sampling parameter. The radial distribution function algorithm was also developed further to ease in the interpretation. The number of curves could thereby be reduced by showing elements, rather than single and molecular ions (of which there were several different kinds). The improvement of the algorithm also allowed interpretation of signs regarding the stoichiometry of SiNy. With a combination of analytical transmission electron microscopy and APT we show Si segregation on the nanometer scale in arc-deposited Ti0.92Si0.0815N and Ti0.81Si0.1915N thin films. APT composition maps and proximity histograms generated from Ti-rich domains show that the TiN contain at least ~2 at. % Si for Ti0.92Si0.08N and ~5 at. % Si for Ti0.81Si0.19N, thus confirming the formation of solid solutions. The formation of relatively pure SiNy domains in the Ti0.81Si0.19N films is tied to pockets between microstructured, columnar features in the film. Finer SiNy enrichments seen in APT possibly correspond to tissue layers around TiN crystallites, thus effectively hindering growth of TiN crystallites, causing TiN renucleation and thus explaining the featherlike nanostructure within the columns of these films.
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| 6. |
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| 7. |
- Kennedy, Beatrice, 1982-
(författare)
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Childhood bereavement, stress resilience, and cancer risk : an integrated register-based approach
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Accumulating evidence suggests that psychosocial stress and susceptibility to stressful exposures – stress resilience – influence the risk of various health outcomes, but the potential link with cancer occurrence is unclear. The aims of this thesis were to test if loss of a close relative, a marker of severe psychological stress, and stress resilience measured during late adolescence are associated with cancer risk later in life, as well as to explore potential underlying mechanisms. National registers provided information on childhood bereavement, defined as death of a first-degree relative, as well as a measure of psychological functioning relevant to stress resilience that was obtained from mandatory military enlistment assessments. In a cohort comprising all individuals born in Sweden during 1961-2002, we found that bereavement during childhood (up to age 18 years) was associated with increased risks of HPVrelated malignancies and pancreatic cancer. Parental loss during early adulthood (ages 18-40 years) also entails a raised risk of pancreatic cancer as well as for gastric and lung cancer. In a cohort of men born during 1973-1983, we observed that childhood bereavement is also associated with low stress resilience during late adolescence. In our third cohort study, comprising men born during 1952-1956, we found that low stress resilience compared with high, was associated with 5-fold and 3-fold increased risks of subsequent liver and lung cancer, respectively. In contrast, low stress resilience is associated with reduced risks for prostate cancer and malignant melanoma. Finally, in a cohort of twin conscripts born during 1959-1985 who completed a survey in 2005- 2006 covering use of addictive substances, we found that low stress resilience was also associated with a raised occurrence of hazardous use of alcohol, alcohol dependence, cigarette smoking and nicotine dependence, as well as with other drug use. We conclude that the observed links with cancer risk for stressful exposures and low stress resilience, may be explained, at least in part, by disadvantageous health behavior.
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| 8. |
- Strand, Mårten, 1982-
(författare)
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The discovery of antiviral compounds targeting adenovirus and herpes simplex virus : assessment of synthetic compounds and natural products
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a need for new antiviral drugs. Especially for the treatment of adenovirus infections, since no approved anti-adenoviral drugs are available. Adenovirus infections in healthy persons are most often associated with respiratory disease, diarrhea and infections of the eye. These infections can be severe, but are most often self-limiting. However, in immunocompromised patients, adenovirus infections are associated with morbidity and high mortality rates. These patients are mainly stem cell or bone marrow transplantation recipients, however solid organ transplantation recipients or AIDS patients may be at risk as well. In addition, children are at higher risk to develop disseminated disease.Due to the need for effective anti-adenoviral drugs, we have developed a cell based screening assay, using a replication-competent GFP expressing adenovirus vector based on adenovirus type 11 (RCAd11GFP). This assay facilitates the screening of chemical libraries for antiviral activity. Using this assay, we have screened 9800 small molecules for anti-adenoviral activity with low toxicity. One compound, designated Benzavir-1, was identified with activity against representative types of all adenovirus species. In addition, Benzavir-1 was more potent than cidofovir, which is the antiviral drug used for treatment of adenovirus disease. By structure-activity relationships analysis (SAR), the potency of Benzavir-1 was improved. Hence, the improved compound is designated Benzavir-2. To assess the antiviral specificity, the activity of Benzavir-1 and -2 on both types of herpes simplex virus (HSV) was evaluated. Benzavir-2 displayed better efficacy than Benzavir-1 and had an activity comparable to acyclovir, which is the original antiviral drug used for therapy of herpes virus infections. In addition, Benzavir-2 was active against acyclovir-resistant clinical isolates of both HSV types.To expand our search for compounds with antiviral activity, we turned to the natural products. An ethyl acetate extract library was established, with extracts derived from actinobacteria isolated from sediments of the Arctic Sea. Using our screening assay, several extracts with anti-adenoviral activity and low toxicity were identified. By activity-guided fractionation of the extracts, the active compounds could be isolated. However, several compounds had previously been characterized with antiviral activity. Nonetheless, one compound had uncharacterized antiviral activity and this compound was identified as a butenolide. Additional butenolide analogues were found and we proposed a biosynthetic pathway for the production of these compounds. The antiviral activity was characterized and substantial differences in their toxic potential were observed. One of the most potent butenolide analogues had minimal toxicity and is an attractive starting point for further optimization of the anti-adenoviral activity.This thesis describes the discovery of novel antiviral compounds that targets adenovirus and HSV infections, with the emphasis on adenovirus infections. The discoveries in this thesis may lead to the development of new antiviral drugs for clinical use.
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| 9. |
- Udumyan, Ruzan, 1971-
(författare)
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Stress susceptibility, beta-blocker use and cancer survival
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Accumulating evidence suggests that chronic stress may influence tumour biology through activation of neuroendocrine pathways and thus impair survival. However, measuring stressful exposures and their influence on health is challenging, partly due to substantial inter-individual variation in stress susceptibility. The thesis aimed to explore whether stress resilience and use of β-adrenergic receptor blockers, which are implicated in regulation of neuroendocrine stress response pathways, are linked to survival after a primary cancer diagnosis using data from Swedish national registers. In a cohort of male cancer patients born during 1952-1956 who had their stress resilience assessed during a mandatory conscription examination in late adolescence, low compared with high stress resilience was associated with a higher overall mortality rate. Statistically significant reductions in survival were observed among men with carcinomas of the oropharynx, prostate, upper respiratory tract, and Hodgkin’s lymphoma. In a cohort of patients diagnosed with pancreatic adenocarcinoma during 2006-2009, β-blocker users had a lower pancreatic cancer mortality rate than non-users, particularly among patients without distant metastases at diagnosis. In a cohort of patients diagnosed with non-small cell lung cancer during 2006-2014, there was no clear association between β-blocker use and lung cancer survival, but we cannot exclude the possibility of associations in some sub-groups defined by histology, stage and β-blocker types. In a cohort of patients diagnosed with hepatocellular carcinoma during 2006-2014, β-blocker use was associated with lower liver cancer mortality, particularly among patients with localised disease. A higher-magnitude inverse association was observed for non-selective β-blocker use. In conclusion, greater stress resilience and β-blocker use are associated with improved survival among patients with some cancer types, and this may be explained by a variety of pathways.
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| 10. |
- Dragisic, Zlatan
(författare)
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Completing the Is-a Structure in Description Logics Ontologies
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The World Wide Web contains large amounts of data and in most cases this data is without any explicit structure. The lack of structure makes it difficult for automated agents to understand and use such data. A step towards a more structured World Wide Web is the idea of the Semantic Web which aims at introducing semantics to data on the World Wide Web. One of the key technologies in this endeavour are ontologies which provide means for modeling a domain of interest.Developing and maintaining ontologies is not an easy task and it is often the case that defects are introduced into ontologies. This can be a problem for semantically-enabled applications such as ontology-based querying. Defects in ontologies directly influence the quality of the results of such applications as correct results can be missed and wrong results can be returned.This thesis considers one type of defects in ontologies, namely the problem of completing the is-a structure in ontologies represented in description logics. We focus on two variants of description logics, the EL family and ALC, which are often used in practice.The contributions of this thesis are as follows. First, we formalize the problem of completing the is-a structure as a generalized TBox abduction problem (GTAP) which is a new type of abduction problem in description logics. Next, we provide algorithms for solving GTAP in the EL family and ALC description logics. Finally, we describe two implemented systems based on the introduced algorithms. The systems were evaluated in two experiments which have shown the usefulness of our approach. For example, in one experiment using ontologies from the Ontology Alignment Evaluation Initiative 58 and 94 detected missing is-a relations were repaired by adding 54 and 101 is-a relations, respectively, introducing new knowledge to the ontologies.
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