| 1. |
- Elmarghani, Ebraheem M.
(författare)
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Enterococcal distribution and responses toenvironmental waters
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The release of antibiotics and pharmaceuticals into environmental waters contribute to the increasing risk of antibiotic resistant bacteria. The spread of antibiotic resistant bacteria in the environment increases the health risks to the community. Enterococci are fecal indicator bacteria (FIB) in aquatic environments for determining water quality. In order to study enterococcal distribution and their response to environmental waters, we first screened for fecal indicator bacteria and their antibiotic resistance. Samples were collected from different locations of inland waters near Örebro city, Sweden at 4 time points during 2010 and 2011. Waters were filtered and the bacteria were cultured on selective media. We observed that the distribution of fecal indicator bacteria was higher at Svartån at Naturens Hus (≤705 CFU/100 ml for enterococci and ≤5867 CFU/100 for E. coli) near the effluent of the wastewater treatment plant (WWTP) than other locations tested. The eastern side of Hjälmaren lake, Storhjälmaren, had the lowest number of FIB (0 CFU/100 ml for enterococci and ≤2 CFU/100 ml for E.coli). Isolated E. coli, E. faecalis and E. faecium were evaluated for antibiotic resistance. We observed that ≤18% of E. coli environmental isolates and 12% of E. faecium and E. feacalis isolates were resistant to antibiotics during 2010 and 2011. Fifteen percent of these were multi antibiotic resistant (MAR) enterococci in 2010 and 31% in 2011. Tetracycline resistance was the most widespread antibiotic resistance found in FIB insolates. Extended spectrum β-lactamase expressing E. coli strains were found to also be MAR. Vancomycin and imipenem resistance was found in E. faecium isolate. Our results suggest that WWTP contributes to the distribution of FIB and antibiotic resistance. Secondly we aimed to evaluate the cellular responses of human and bacterial cells in environmental waters. We found that the pro-inflammatory response (IL-1β and TNF-α) of THP-1 cell was significantly higher in Svartån at Naturens Hus downstream of WWTP than the other locations. Based on this we evaluated E. feacalis responses to the same water. There were no statistical significant changes in gene response found in E. feacalis isolates, suggesting that environmental waters contain unidentified substances can effect on human cells responses but not bacteria. In this report we conclude that transferring of MAR strains in the environmental waters were increased annually in enterococci and E. feacalis did not initiate a response to the unknown substances that are present in river.
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| 2. |
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| 3. |
- Sjödin, Carina, 1964-
(författare)
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User-involved service innovation : Three participating perspectives on co-creation
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The involvement of customers and other stakeholders in the innovation process is proposed to be a key success factor and something that makes companies more competitive. As a consequence, more and more organizations alter their innovation strategy accordingly. In order for a company to open up innovation processes, it is vital to foster a practice where there is openness for external ideas and knowledge. However, when external ideas meet internal innovation practices complex organizational situations appear. Creativity, for example, involves co-dependence of other persons’ strategies and actions. New roles for those involved affect hierarchies and knowledge sharing opportunities.This thesis involves three different perspectives of the same process provides an opportunity to study both individual and structural challenges. This research aims to identify on-going challenges for an organization during the transformational processes that adjustment from a traditional product innovation structure to an open service innovation culture implies. This qualitative case study involves two main cases and three supporting cases and aims to understand how users and other external parties, top management and middle managers experience open innovation processes. The results describe interactions between organizations and users or external stakeholders as well as internal interactions within the organization. Top management were dedicated to the idea of increased openness, but detected structural issues to deal with in order to implement user involved innovation. Among middle management, some individual aspects such as attitudes and relational issues matter, as well as organizational structures and practices. Users had mixed opinions about their participation in the process. Favorable experiences, such as benevolence and deepened relationships, were balanced by un-favorable experiences such as incapability and intrusion. Different dimensions of openness regarding open innovation practice are discussed. In this work a relational focus is emphasized. The findings assist managers in their work to create conditions for open innovation. Managers can benefit from this research by getting a better understanding of how different stakeholders’ experience co-creation of value. This is relevant for innovation managers in the process of redesigning innovation processes to understand different aspects of the interactions involved.
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| 4. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 5. |
- Wellhagen, Gustaf, 1988-
(författare)
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Pharmacometric Investigations of Prediction Precision and Advances of Models for Composite Scale Data
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Clinical trials are needed to evaluate new treatments. In late-stage clinical trials, failures are mostly due to lack of efficacy. Fit-for-purpose analysis methods will likely increase the success rates and advance drug development by providing higher precision to support decisions such as go/no-go, dose selection, or sample size. This thesis presents new methods for analysis of composite scale data, and comparisons of prediction precision of new and standard analysis methods. Composite scale data arise from questions/items rated with integers. A total score can be derived, which is discrete and bounded. Item response theory (IRT) models are the natural choice for such data, since they use the item-level information. However, when only the total score is available they cannot be used. The bounded integer (BI) model is a new method for discrete, bounded outcomes. With composite scale total score data, it had superior fit compared to standard methods, because it respects the nature of the data. Further, a new method, formally linking IRT models to models for total score, was developed. The expected mean and variance, given an IRT model, was implemented in BI and continuous variable models. This improved fit, allowed estimation of IRT parameters, and allowed comparison of different model types.The prediction precision of both outcome and parameters were investigated with different methods, ranging from t-test to mechanistic pharmacometric models, for composite scale and continuous data. The most suitable method depended on the purpose, for example mechanistic models are superior at establishing a drug’s site of action.In conclusion, the choice of method should be based on the primary question, and also the data collected. The method should not be more complex than necessary, and the nature of the data respected. This thesis will help modellers select the most appropriate analysis method for a problem at hand.
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| 6. |
- Barthel, Stephan, 1968-
(författare)
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Recalling Urban Nature : Linking City People to Ecosystem Services
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Societal development is dependent on the generation of ecosystem services (ES) to sustain it; however, many ES are degrading. This thesis investigates how social-ecological features behind practices of actor groups shape the generation of ES. The empirical basis is case studies in the urban landscape of Stockholm, Sweden, and the methodological approach is interdisciplinary. Paper I shows that the urban landscape owes it current flow of ES to co-evolutionary processes and that governance with the aim of sustaining ES must take into account historical property rights and the involvement of a diversity of actor groups, as well as ecological processes of the larger landscape. Paper II studies allotment gardens, cemeteries and city parks in relation to the generation of pollination, seed dispersal and pest regulation. Differences in social features behind practice are reflected primary as higher abundance of pollinators in the informally managed allotment gardens and as differences in the compositions of seed dispersers and insectivores’ birds. Thus, voluntary and often ignored actor groups, motivated by sense-of-place, support the generation of some ES here. Paper III shows how practice, linked to ES generation, is retained and stored among allotment gardeners, and modified and transmitted through time, by means of social-ecological memory (SE-memory). SE-memory is an emergent property of a dual process of participation and reification and it facilitates monitoring of local change and links practice, often in habits, to place specific processes that underlie provisioning ES. Paper IV explores how spatial scale mismatches between ecological process and processes of management can be bridged by a spatially explicit and flexible social network structure of governance. Urban ES are a product of human driven co-evolution, consequently sustaining ES in urban landscapes is not about conservation without people, but shaped by and dependent on management practice by people. Practice that links to generation of ES are facilitated by SE-memory of local actors that holds long term management rights. Consequently, local communities of ecosystem practice, which contribute to the production of ES should explicitly be taken into account in urban green governance.
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| 7. |
- Berg, Håkan, 1972-
(författare)
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Teleost reproduction: Aspects of Arctic char (Salvelinus alpinus) oocyte growth and maturation
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In all vertebrate species, reproduction is a hormonally controlled process, important for growth and maturation of gonads and germ cells. Production of functional germ cells is of outmost importance to secure the survival of a species. Fish comprises 50% of the known vertebrates and are found in aquatic habitats all over the world. Even though fish have evolved a wide variety of morphological and physiological characteristics, due to large differences in the living environment, the growth an maturation of germ cells follows the same pattern in all species. In this thesis the focus has been directed on oocyte growth and development in Arctic char (Salvelinus alpinus), and if stress might inflict disturbances on the reproductive systems.All sexually mature female egg laying vertebrates produces yolky eggs surrounded by an eggshell. Production of yolk and egg shell is under estrogenic control and it is known that production of egg components can be induced in male and juvenile fish by estrogenic substances. Many manmade chemicals have been found to interfere with hormonally controlled processes. Therefore production of the egg yolk precursor, vitellogenin (VTG), and the egg shell components, vitelline envelope proteins (VEP), have been used as biomarkers for estrogenic effect. Exposure to endocrine disrupting substances (EDS) does not only give rise to hormonal effects on the organism, but in addition it also gives rise to an increase in stress hormone, cortisol (F), levels.It is evident that a wide variety of substances may affect Arctic char oocyte growth and maturation. VTG and VEP production is found to be under dose dependent estrogenic control, but the production was directly affected by F. Under natural condition it has been found that F increases towards ovulation. Even though both VTG and VTG is under estrogenic control, these studies showed that stress lead to a decrease of VTG while the VEP production increased. These effects was only observed on protein levels indicating that a post transcriptional down regulation of VTG production is mediated by F in Arctic char.In order for an egg to become fertilizatible, it must undergo a maturation phase. This maturation phase is primarily induced by gonadotropins, which in turn induce the production of species specific maturation inducing substances (MIS). To investigate oocyte development in Arctic char a characterization of its MIS receptor was made. The MIS receptor is localized on the oocyte surface and displays a single class of high affinity and low capacity binding sites. The binding moieties displays association and dissociation kinetics typical of steroid membrane receptors.Even though high specificity for Arctic char MIS was observed, it was found that some EDS bind to the Arctic char oocyte membrane receptor. This suggest that certain EDS might affect oocyte maturation and thereby might alter the reproductive success. Furthermore, it was found that F did not bind to the MIS receptor in Arctic char. It is therefore suggested that oocytes are more sensitive to stress during the growth phase than during maturation
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| 8. |
- Boisvert, Catherine Anne, 1978-
(författare)
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The Origin of Tetrapod Limbs and Girdles: Fossil and Developmental Evidence
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Around 375 million years ago, the first tetrapods appeared, marking one of the most important events in vertebrate evolutionary history. The fin to limb transition saw the appearance of fingers and a weight bearing pelvic girdle. While very little research has been done on the evolution of the tetrapod pelvic girdle, a fair amount has been done on the origins of fingers but some aspects remained controversial. A combination of palaeontology, developmental biology and comparative morphology was therefore used in this thesis to better understand the fin to limb transition. The pectoral fin of Panderichthys, a sarcopterygian fish closely related to tetrapods was CT-scanned and modeled in three dimensions and its pelvic girdle and fin were examined with traditional techniques. This information from the fossil record was integrated with comparisons of the development of the Australian lungfish, Neoceratodus forsteri, our closest living fish relative and the axolotl (Ambystoma mexicanum), a salamander representing well the condition of early tetrapods. Development of bone and cartilage was studied through clearing and staining and development of skeletal muscles through immunostaining. In situ hybridizations were performed on the lungfish to study the expression of Hoxd13, associated with the formation of digits in tetrapods. This work shows that the late expression phase of Hoxd13 is present in Neoceratodus and is associated with the formation of radials. Redescription of the pectoral fin of Panderichthys reveals that distal radials are present, which, in addition to other information, lead us to conclude that digits are not novelties in tetrapods but rather have evolved from the distal radials present in the fins of all sarcopterygian fish. The earliest tetrapods lack a full set of wrist + carpals/ankle + tarsal bones. Here, we propose that this region of the limbs evolved after fingers and toes through an expansion of the region between the proximal limb bones and the digits. As for the pelvic girdle, it is very primitive in Panderichthys but comparison of its development in Neoceratodus and Ambystoma suggest that the ischium evolved through the posterior expansion of the pubis and the ilium, through an elongation of the iliac process already present in sarcopterygian fishes. The results of this thesis help to better understand the fin to limb transition and show that it is more gradual than previously believed.
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| 9. |
- Carlsson, Per, 1969-
(författare)
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Surface Engineering in Sheet Metal Forming
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent years, surface engineering techniques have been developed in order to improve the tribological performance in many industrial applications. In sheet metal forming processes, the usage of liquid lubricants can be decreased by using self lubricated tribo surfaces which will result in more environmentally friendly workshops. In the present work two different concepts, i.e. the deposition of thin organic coatings on the steel sheet and PVD coatings on the tool, have been evaluated. The sheet materials investigated include Zn and 55%Al-Zn metal coated steel sheet, which in general are difficult materials to form under dry conditions since they are sticky and thus have a high tendency to adhere to the tool surface. The PVD coatings include CrN, TiN and various DLC coatings. The work comprises tribo testing and post test characterisation using surface analytical techniques in order to evaluate the tribological properties of the tribo surfaces. The tribological tests of different tribo couples were conducted by using modified scratch testing and ball-on-disc testing. From these test results different friction and wear mechanisms have been identified. The deposition of thin organic coatings on the steel sheet metal has been found to be promising in order to control the friction and to avoid metal-metal contact resulting in galling. However, it has been found that the tribological characteristics of organic coated steel sheet are strongly influenced by coating chemical composition, the substrate surface topography and the coating thickness distribution. The performance of the PVD coatings depends mainly on the chemical composition and topography of the coated surface. By choosing PVD coatings such as diamond like carbon (DLC) low and stable friction coefficients can be obtained in sliding contact against Zn. Surface irregularities such as droplet-like asperities may cause an initial high friction coefficient. However, after a running in process or by polishing the PVD coating low friction coefficients can be obtained resulting in a stable sliding contact. The combination of imaging (optical profilometry, LOM, SEM) and chemical analytical techniques (EDS, AES, ToF-SIMS) gave valuable information concerning the friction and wear properties of the tribo surfaces investigated.
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| 10. |
- El Marghani, Ahmed
(författare)
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Regulatory aspects of innate immune responses
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Activation of innate immunity is regulated by a variety of signaling molecules within the immune cells. The present thesis was aimed to improve our understanding of innate signaling mechanism and their possible use as bio-indicators of exposure and disease. The first part of the thesis deals with the involvement of TOM1L1 (Target of Myb1 like 1) in innate immune signaling and regulation of inflammatory cytokines in immune cells (study I and II). The initial event of T-cells activation depend on the recruitment of Src family kinases Fyn and Lck, leading to interleukine-2 (IL-2) production in T cells. Understanding the regulatory aspects of IL-2 induction in T-cells is of importance as IL-2 is a key regulator for T-cell proliferation and survival. Interaction screening indicated the ability of TOM1L1 protein to interact with Fyn, and Lck, that is important for IL-2 production in Jurkat T-cells. TOM1L1 silencing decreased the levels of CD3/CD28 dependent induction of IL-2 in Jurkat T-cells, and LPS dependent induction of TNF-α in THP-1. Furthermore, overexpression of TOM1L1 in Jurkat T-cells causes an increase of STAT3 expression. This was accompanied by an increase in the levels of IL-1β dependent induction of IL-6 and TNF-α in THP-1 cells. These results indicate that TOM1L11 participate in regulation of innate immune response. The second part of the thesis deals with development of innate immune signaling responses used as a diagnosis tools for disease and exposure (study III and IV). Inflammatory diseases are associated with innate immune reactions. In response to inflammation, the immune cells release inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-10, TNF-α and CXCL8. These cytokines are regulated by stress related kinases include MAP kinase proteins such as ERK1-2, JNK, and MAPK p38, through activation of transcription factors AP-1, ATF-2, and NF-AT. In a clinical study, it was observed that activated MAPK p38 has a potential role in the regulation of IL-10 expression in intermittent claudication. However, expression of IL-10 and MAPK p38 was opposed in stable angina group. Therefore, targeting MAPK p38 in inflammatory disease such as cardiovascular diseases, diabetes, and rheumatoid arthritis might be useful in development of treatment strategies. Innate immune reactions can also be used to monitor stress related inflammatory responses following environmental exposure of immune cells. Inflammatory responses of exposure were studied by in vitro exposure to waters from sewage treatment works and recipient waters. The analysis shows that exposure to inland waters can result in activated immune responses and that these responses are both site dependent and vary over time.
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