| 1. |
- Marchesi, Silvia, MD, 1985-
(författare)
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The effect of mechanical ventilation on abdominal organs : Analysing the role of PEEP and perfusion.
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The effect of mechanical ventilation on abdominal organs is not well understood and investigated yet. Previous studies, using an animal sepsis-like model, found an association between mechanical ventilation (MV) and abdominal edema and inflammation.The presented thesis was aimed to investigate the role of perfusion in edema formation and inflammation, and to study the abdomen during mechanical ventilation in an ARDS model to reduce the confounding effect of inflammation related to sepsis.Methods: In the first paper presented, inflammation and edema in the abdomen were investigated in an endotoxin model. The study subjects were divided into two groups with different mean arterial pressures (MAP), another small group of healthy controls were studied as well. MRI analyses were used to measure perfusion in the different abdominal organs. In the second paper presented, differences in abdominal edema and inflammation were assessed in two groups of subjects, one group underwent MV and one group had spontaneously breathing.Results: In the first study, MRI analyses confirm that the group with higher MAP had better perfusion than the low MAP group. In the liver, perfusion was lower in LowMAP group compared to HighMAP group, but the HighMAP group had lower perfusion than the healthy controls. However, in the other studied organs HighMAP group and healthy controls had similar perfusion.Edema did not differ between the groups. Inflammation was globally higher in LowMAP group and correlated with hemodynamics. TNFα in liver tissue and portal vein serum correlated with intra-abdominal pressure (IAP).In the second study, the cytokine concentration was higher in serum in the MV group. MV did not increase abdominal edema or inflammation, compared to spontaneous breathing. Discussion and conclusion: Abdominal edema and inflammation are multifactorial phenomena, and many elements have to be included in the analysis. Perfusion plays an important role in determining inflammation and IAP. MV per se was not found to be related to increased edema and inflammation. In a previous study, the role of different levels of PEEP and different respiratory rate between mechanically ventilated and spontaneously breathing animals were not analyzed, but could have contributed to the results. The efforts made in this study to maintain similar respiratory rate and PEEP in both groups, could have contributed to the presented results.It is important to underline that, even if MV was not related to inflammation in abdomen, it was related to an increase in systemic inflammation, most probably because of an enhanced lung production of inflammatory mediators.Further studies, focusing on the role of respiratory rate and PEEP on abdomen, as well as the analysis of the inter-relations among inflammation, perfusion and edema, are needed to increase the pathophysiological understanding of these phenomena.
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| 2. |
- Hamdan, Mohammed, 1978-
(författare)
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Effects of temperature and terrestrial carbon on primary production in lake ecosystems
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Climate warming is predicted to affect northern lake food webs in two ways: (1)directly via changes in water temperature and ice conditions, and (2) indirectlyvia changes in catchment characteristics and processes that influence input ofallochthonous coloured dissolved organic matter (cDOM) and nutrients. Input ofcDOM increases carbon dioxide (CO2) availability, causes brownification andreduced light conditions, and may increase nutrient availability especially forpelagic primary producers. Increased water temperature and light penetrationand longer ice-free periods affect metabolic rates. These changes are expected toinfluence gross primary production (GPP) and growth of higher trophic levels.However, majority of studies focus on pelagic processes and net effects at wholelake scale is not well understood. Consequently, the lack of knowledge of whatfactors control benthic GPP makes predictions of net effects of climate change onwhole-ecosystem GPP spurious. The aim of this thesis was to experimentally testeffects of warming and increased input of allochthonous cDOM on habitatspecific and whole-ecosystem GPP in lakes. First, by manipulating the CO2concentrations in large scale pond ecosystems, we showed that increased CO2stimulated whole-ecosystem GPP. In a separate incubation study with naturallake sediments in a boreal lake, we tested the role of CO2 as a limiting factor forbenthic GPP under different light levels. The results showed that CO2 supplystimulated benthic GPP at high but not at low light availability, suggesting thatbenthic GPP can be CO2-limited. In the same experimental pond ecosystems, thecombined effect of increased allochthonous cDOM and warming (+3.5°C) on GPPwas studied. The results showed that cDOM input decreases whole-ecosystemGPP, mainly as a result of decreased benthic GPP due to light limitation not fullycounteracted by an increase in pelagic GPP under ambient conditions. Warmingon the other caused a hump shaped increase in whole-ecosystem GPP withincreasing cDOM input mainly due to a positive response in pelagic GPP due torelaxed nutrient limitation. Finally, by manipulating the fish consumer biomassin the same experimental pond ecosystems we showed that whole-ecosystem GPPcan be controlled by top-down effects under warm (+ 3.0°C) but not ambienttemperature conditions. The decline in whole-ecosystem GPP was mainlyattributed to a warming-stimulated consumer-driven trophic cascade in thepelagic habitat and top-down control by zooplankton on phytoplankton growth,while no corresponding cascade was evident in the benthic habitat.Taken together, the results suggest that climate change impacts, as increasinginputs of cDOM, warming and changes in food webs, have different effects onhabitat specific GPP and alone or in combination have impacts on whole-lakeGPP. This thesis offers important insights to better understand the factors thatcontrol lake GPP and to predict future lake ecosystem responses to environmentalchange.
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| 3. |
- Kristoffersson, Anders, 1985-
(författare)
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Study Design and Dose Regimen Evaluation of Antibiotics based on Pharmacokinetic and Pharmacodynamic Modelling
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Current excessive use and abuse of antibiotics has resulted in increasing bacterial resistance to common treatment options which is threatening to deprive us of a pillar of modern medicine. In this work methods to optimize the use of existing antibiotics and to help development of new antibiotics were developed and applied.Semi-mechanistic pharmacokinetic-pharmacodynamic (PKPD) models were developed to describe the time course of the dynamic effect and interaction of combinations of antibiotics. The models were applied to illustrate that colistin combined with a high dose of meropenem may overcome meropenem-resistant P. aeruginosa infections.The results from an in vivo dose finding study of meropenem was successfully predicted by the meropenem PKPD model in combination with a murine PK model, which supports model based dosage selection. However, the traditional PK/PD index based dose selection was predicted to have poor extrapolation properties from pre-clinical to clinical settings, and across patient populations.The precision of the model parameters, and hence the model predictions, is dependent on the experimental design. A limited study design is dictated by cost and, for in vivo studies, ethical reasons. In this work optimal design (OD) was demonstrated to be able to reduce the experimental effort in time-kill curve experiments and was utilized to suggest the experimental design for identification and estimation of an interaction between antibiotics.OD methods to handle inter occasion variability (IOV) in optimization of individual PK parameter estimates were proposed. The strategy was applied in the design of a sparse sampling schedule that aim to estimate individual exposures of colistin in a multi-centre clinical study. Plasma concentration samples from the first 100 patients have been analysed and indicate that the performance of the design is close to the predicted.The methods described in this thesis holds promise to facilitate the development of new antibiotics and to improve the use of existing antibiotics.
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| 4. |
- Thore, Carl-Johan
(författare)
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Optimal Design of Neuro-Mechanical Networks
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns modeling and optimal design of Neuro-Mechanical Networks. A Neuro-Mechanical Network (NMN) can be described as an active mechanical structure, made up from a network of simple but multifunctional elements that interact with their nearest neighbors. The concept is of mechatronic character as it involves integration of actuators, sensors, signal processing, and control, into a mechanical structure. The first part of the thesis consists of three chapters. The first of these chapters contains a brief introduction to the NMN-concept and the present work. In the second chapter, the particular type of NMNs considered here is described in more detail, and the third chapter constitute a brief survey of some works relevant to optimization of active structures, including enabling technologies and static and dynamic shape control. The second part of the thesis consists of two papers, where the first paper describes optimal design of NMNs for static shape control, while the second paper is concerned with optimal design of structures that exhibit oscillatory motion.
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| 5. |
- Adams Lyngbäck, Liz, 1966-
(författare)
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Experiences, networks and uncertainty : parenting a child who uses a cochlear implant
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this dissertation project is to describe the ways people experience parenting a deaf child who uses a cochlear implant. Within a framework of social science studies of disability this is done by combining approaches using ethnographic and netnographic methods of participant observation with an interview study. Interpretations are based on the first-person perspective of 19 parents against the background of their related networks of social encounters of everyday life. The netnographic study is presented in composite conversations building on exchanges in 10 social media groups, which investigates the parents’ meaning-making in interaction with other parents with similar living conditions. Ideas about language, technology, deafness, disability, and activism are explored. Lived parenting refers to the analysis of accounts of orientation and what 'gets done' in respect to these ideas in situations where people utilize the senses differently. In the results, dilemmas surrounding language, communication and cochlear implantation are identified and explored. The dilemmas extend from if and when to implant, to decisions about communication modes, intervention approaches, and schools. An important finding concerns the parents’ orientations within the dilemmas, where most parents come up against antagonistic conflicts. There are also examples found of a development process in parenting based on lived, in-depth experiences of disability and uncertainty which enables parents to transcend the conflictive atmosphere. This process is analyzed in terms of a social literacy of dis/ability.
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| 6. |
- Dreifaldt, Mats, 1959-
(författare)
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Conduits in coronary artery bypass grafting surgery : Saphenous vein, radial and internal thoracic arteries
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A novel technique for saphenous vein (SV) graft harvesting, the No-touch technique (NT), has been developed at the Dept. of Cardiovascular surgery, Örebro University hospital. With NT the SV is harvested with a pedicle of surrounding tissue. This avoids graft spasm and eliminates the need for distension. The surrounding tissue acts as a structural support and is a rich source of vaso-dilating agents. A randomized controlled trial (RCT) has shown a significantly higher patency rate for NT SV grafts compared to SV grafts harvested with conventional technique (CT). This thesis evaluates some of the properties of the surrounding tissue and compares patency rates between NT SV and radial artery (RA) grafts and patency rates for internal thoracic artery (ITA) grafts harvested with and without surrounding tissue. Paper I investigated vasa vasorum (VV) in SV grafts and showed that the NT preserves an intact VV whereas CT does not. This could be one of the mechanisms underlying the improved patency for NT SV grafts. Paper II evaluated VV and associated nitric oxide (NO) in SV and arterial grafts. SV grafts showed a higher number and larger VV, which correlated with NO production, compared to arterial grafts. NT SV grafts showed higher activity for e-NOS compared to CT SV grafts. Paper III is a RCT comparing patency rates between NT SV and RA grafts, three years after surgery, showing a significantly higher patency rate for NT SV grafts. Paper IV is a RCT comparing patency rates for ITA graft harvested with and without surrounding tissue and did not show any difference between graft preparations. In conclusion, the NT for SV graft harvesting preserves an intact vasa vasorum and associated NO production. NT SV grafts show a higher patency rate than RA grafts. Harvesting of ITA with or without surrounding tissue does not affect patency rate.
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| 7. |
- Engström, Annica, 1967-
(författare)
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Dimmornas bro : En berättelse om konstruktionen och iscensättandet av kliniska adjunkter
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation is a study of a relatively new teacher function in nurse education, a teacher function that can be called clinical teacher, link lecturer, link teacher or lecturer involved in practice. The study departs from a constructivist perspective and the aim is to study the introduction, performance and regulation of this teacher function. The material consists of internationally and nationally published research 1978-2009, reports from the authorities, job ads for clinical teachers, job descriptions and contracts, archive material, evaluation studies, professional journals, texts on the Internet and 15 interviews with clinical teachers in Sweden. Using discourse analysis this material is studied in terms of interpretive repertoires, subject positions and ideological dilemmas. The primary focus of this dissertation concerns what problems the new teacher function is supposed to solve, how the problem should be solved, the effects of the chosen solutions and what´s staged, challenged and reproduced. Secondly, this dissertation highlights what categories of teachers are required and in demand for the new teacher function, how the teachers themselves manage their function and how the teacher function is maintained and challenged. The analysis identifies and highlights current interpretive repertoire, teachers possible subject positions and ideological dilemmas and how they are governed and challenged in the teaching function.
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| 8. |
- Heuman, Anna, 1990-
(författare)
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Negotiating standard language ideology : Metalinguistic discussions in mundane, online interaction
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates how ordinary language users enact language policy and thus negotiate (standard) language ideology in mundane, online interaction. The language policy work is found in metalinguistic discussions on various social media. The discussions have been triggered by deviations from standard written language, mostly on the level of orthography. The discussions mainly target different aspects of standard language ideology. The three studies included in this compilation thesis identify discursive strategies and reveal the contradictory ideologies underpinning the discussions.The discussions are analysed with an interactional and procedural focus, highlighting the unfolding negotiations of standard language ideology. The results show that standard language ideology is prevailing which, in turn, enables certain realisations. When drawing on standard norms, the participants can use strategies that do not include explicit arguments. However, the discussions also include contradictions and strategies that challenge traditional standard beliefs. These results illustrate the mundane, vivid metalinguistic negotiations in which standard language ideology is primarily enforced, but also challenged.The results illuminate how standardisation is not a mythical and imperceptible process, but one of constant and visible iteration, also in very mundane situations. Furthermore, the pervasiveness of standard language ideology could make it harder for those who deviate from it to be listened to or even to participate at all. In this way, everyday metalinguistic discussions are one among many language policy activities that can enforce loyalty to the standard variety and its position as unmarked.
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| 9. |
- Karlsson, Emil, 1990-
(författare)
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Optimisation-based scheduling of an avionic system
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Modern computer systems in aircraft are often based on an integrated modular avionic architecture. In this architecture, software applications share hardware resources on a common avionic platform. Many functions in an aircraft are controlled by software and a failure in such software can have severe consequences. In order to avoid malfunction, there are many aspects to consider. One aspect is to ensure that the activities in the system is done at the right time with the right resources. To analyse if this is possible or not is often called schedulability analysis.When multiple functions are using the same resources, the schedulability analysis becomes increasingly challenging. This thesis focuses on a pre-runtime scheduling problem of an integrated modular avionic system proposed by our industrial partner Saab. The purpose of this problem is to find a feasible schedule or prove that none exists as part of a schedulability analysis.For the system that we study, there are two major challenges. One is that task and communication scheduling are integrated and the other is that there is a large amount of tasks to schedule. For the largest instances, there are more than 10 000 tasks on a single module. In order to solve such problems, we have developed a matheuristic. At the core of this matheuristic is a constraint generation procedure designed to handle the challenges of the scheduling problem.The constraint generation procedure is based on first making a relaxed scheduling decision and then evaluating this in a separate problem where a complete schedule is produced. This yields a decomposition where most technical details are considered in the relaxed problem, and the actual scheduling of tasks is handled in a subproblem. Both the relaxed problem and the subproblem are formulated and solved as mixed integer programs.The heuristic component of the matheuristic is that the relaxed problem is solved using an adaptive large neighbourhood search method. Instead of solving the relaxed problem as a single mixed integer program, the adaptive large neighbourhood search explores neighbourhoods through solving a series of mixed integer programs. Features of this search method are that it is made over both discrete and continuous variables and it needs to balance feasibility against profitable objective value.The matheuristic described in this thesis has been implemented in a scheduling tool. This scheduling tool has been applied to instances provided by our industrial partner and to a set of public instances that we have developed. With this tool, we have solved instances with more than 45 000 tasks.
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| 10. |
- Karlsson, Johnny, 1976-
(författare)
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Spill : Om djur, hantverk och nätverk i Mälarområdet under vikingatid och medeltid
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the use of various osseous raw materials in craft activities in the Mälaren region during the Middle Ages. Places studied are: Birka, Sigtuna, Nyköping, Strängnäs and Uppsala. The aim is to capture both chronological and spatial changes in the use of osseous raw materials. Species and materials used reflect regional as well as international networks and how they change during time. The spatial distribution of waste from craft activities, its materiality and temporality mirror activities in different social contexts. Quantitative and qualitative changes in the handling and exploitation of raw materials reflect varying and changing views of its value and how craft and exchange is affected by both a social and economic agency.In Birka, osseous waste material associated with craft was collected by Hjalmar Stolpe in the 1870s. An examination of the assemblage shows that imported material comprises a significant part of the collection. About a third of the waste consists of imported antler of red deer and reindeer. Red deer is particularly abundant (21%), signifying the importance of southern trading networks. The presence of whalebone can also be linked to south-western trading routes.The waste material collected during excavations in Sigtuna and representing the period c. 980-1300 has a different composition, reflecting different networks and perhaps different means of trade and production. As in Birka, elk antler constitutes the main bulk of the raw material used. Red deer antler is extremely limited, forming less than 1% of the material, appearing continuously though in small amounts from c. 1020-1300. Reindeer antler is distinctly present in the oldest phase, c. 980-1000. This occurrence might represent a relic of the northern network manifested at Birka. An isotopic study indicates an origin in a forested biotope. After this initial phase the use of reindeer antler becomes as rare as that of red deer until the second half of the 12th century, indicating that the antler craft operated on a minor scale without any demand for long-distance trade in raw materials. A change occurs in the last quarter of the 12th century when large quantities of reindeer antler appear once more. Isotope signatures indicate an origin in more mountainous regions. This coincides with the introduction of another traded raw material of an arctic origin: walrus tusk. The craft had become more marked oriented. This is manifested in larger deposits of debris, a wider range of materials used, including bones from various domestic animals, but also the handling and exploitation of the material changes indicating a different view of production, trade and the value of raw materials than previous. This shift coincides with the introduction of minted silver. Western influences are evident both in the material culture and in the faunal assemblage. It is likely that a majority of the reindeer antler as well as the walrus tusk present in these later phases have a Norwegian origin.In the late 1100s and early 1200s craft in osseous material occur in other towns that emerge in the region but it seems to appear in new social contexts. Small assemblages of antler debris have been found in Uppsala, but the activities they represent lack the spatial continuity that exist in contemporary environments in Sigtuna and Strängnäs, indicating short lived occasional activities in a loosely regulated urban environment. Craft activities dependent purely on bone from domestic animals appear in the 1200s in Nyköping, Uppsala and Strängnäs. They represent craft activities in a new social context outside the private sphere of the local elite and instead subordinated other craft activities where domestic animals have been exploited on a large scale beyond the domestic household. Antler craft represents a social practise in the realms of the local elite with a continuity stretching back to the Iron Age. Monetization and an increasingly feudal society redefine social relations and practise. This can be seen in the occurrence of craft in new contexts in the late 1100s and 1200s, reflecting heterogeneity in social and economic functions in and between the towns in the region.
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