| 1. |
- Grossmann, Benjamin
(författare)
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Procedural sedation : Aspects on methods, safety and effectiveness
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Safety and effectiveness are fundamental principles within the healthcare sector to provide quality of care and health improvement for patients. By ensuring that care is provided based on evidence-based knowledge, risks and complications can be minimised and the use of scarce resources optimised. An increasing demand for diagnostic and therapeutic procedures challenges the traditional methods for sedation regarding safety and effectiveness. It is desirable that the fundamental principles are improved when refining existing or developing new sedation methods. In this doctoral thesis, safety and effectiveness were evaluated for adult patient-controlled sedation (PCS) using propofol during two endoscopic procedures: endoscopic retrograde cholangiopancreaticography (ERCP) and flexible bronchoscopy (FB); and different doses of rectal racemic ketamine for paediatric (< 4 years) burn wound care.Methods: Data on vital functions, sedation level, safety interventions, procedure feasibility, patient-reported outcome and experience measures, and recovery, from three clinical randomised controlled trials were collected. Costs of sedation for the endoscopic procedures were compiled in a cost-analysis study.Results: PCS with propofol and bedside anaesthetic personnel was shown to be a safe and effective alternative method of sedation during ERCP and FB compared with intravenous sedation with midazolam. The PCS method gives stable cardiorespiratory conditions with few adverse events and interventions, with a low risk of oversedation. PCS offers similar (FB) or better (ERCP) procedure feasibility and patient satisfaction during the procedures than midazolam. Recovery after PCS is quick, minimises the risk for prolonged hospitalisation and is thereby a potential cost-saving sedation method. The optimal dose of rectal racemic ketamine, 6 mg/kg with the addition of 0.5 mg/kg midazolam during severely painful procedures, gives minimal risk for outbreaks of pain, offers stable vital signs conditions and allows rapid recovery without affecting procedure feasibility.Conclusions: The sedation method can be adjusted to type of procedure and patient population. PCS with propofol offers an alternative and reliable method for adult sedation during endoscopic procedures, whereas rectal racemic ketamine combined with midazolam provides good conditions for burn care dressing procedures in young children.
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| 2. |
- Nilsson, Andreas, 1974-
(författare)
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Patient-controlled sedation in procedural care
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The need for procedural sedation is extensive and on the increase in numbers of patients. Minor treatments or diagnostic procedures are being performed with inadequate sedation or even without any sedatives or analgesics. Also, sedation techniques that support advanced, high-quality, in-patient care procedures representing easy performance and rapid recovery are requested for increased effectiveness. In this doctoral thesis, patient-controlled sedation (PCS) using propofol and alfentanil for surgical and diagnostic procedures was studied. The overall aim was to study aspects of safety, procedural feasibility and patients’ experiences. The main hypothesis was that PCS using only propofol is a safe and effective method for the induction and maintenance of moderate procedural sedation. The studies included were prospective, interventional, and in some cases, randomized and double-blinded.Data on cardiopulmonary changes, level of conscious sedation (bispectral index and Observer’s assessment of alertness/sedation [OAA/S]), pain, discomfort, anxiety, nausea (visual analogue scales), interventions performed by nurse anaesthetists, surgeons’ evaluation of feasibility, procedure characteristics, recovery (Aldrete score) and pharmacokinetic simulation of concentrations of drugs at the effect site supported the analysis and comparison between PCS and anaesthetist-controlled sedation and propofol PCS with or without alfentanil.PCS can be adjusted to cover a broad range of areas where sedation is needed, which, in this thesis, included burn care, gynaecological out-patient surgery and endoscopic procedures for the diagnosis and treatment of diseases in the bile ducts (endoscopic retrograde cholangiopancreatography [ERCP]). PCS for burn wound treatment demands the addition of alfentanil, but still seems to be safe. PCS was preferred by the patients instead of anaesthetist-controlled sedation. The addition of alfentanil to PCS as an adjunct to gynaecological surgical procedures also using local anaesthesia increases the surgeon’s access to the patients, but impairs safety. Apnoea and other such conditions requiring interventions to restore respiratory function were seen in patients receiving both alfentanil and propofol for PCS. Patients’ experiencing perioperative pain and anxiety did not explain the effect-site concentrations of drugs. Different gynaecological procedures and patients’ weights seemed to best explain the concentrations. For discomfort and pain during the endoscopic procedure (ERCP), propofol PCS performs almost the same as anaesthetist-performed sedation. Overall, as part of the pre-operative procedures, PCS does not seem to be time-consuming. In respect to the perioperative perspective, PCS supports rapid recovery with a low incidence of tiredness, pain, and post-operative nausea and vomiting (PONV).The data suggest that PCS further needs to be adapted to the patient, the specific procedure and the circumstances of sedation for optimal benefit and enhanced safety.
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| 3. |
- Bergens, Oscar, 1991-
(författare)
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Chronic Systemic Inflammation, Body Composition and Physical Activity Behaviours in Older Adults
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ageing is associated with a gradual physical decline accompanied by changes in body composition. The occurrence of a low-grade yet chronic state of systemic inflammation has gained interest for its potential consequences in the ageing process. Importantly, a physically active lifestyle may promote the maintenance of muscle mass, reduction in adipose tissue, and alleviate progression of a chronic pro-inflammatory state. The overall aim of this thesis was to explore relationships between biomarkers of systemic inflammation, body composition, and physical activity behaviours in community-dwelling older adults aged 65 to 70 years.A main finding of the thesis is the existence of associations between body composition and systemic inflammation in older adults, where excess adipose tissue is adversely associated with levels of inflammatory biomarkers in older women. Inverse associations were also observed between muscle mass and levels of pro-inflammatory biomarkers in older women. This thesis also highlights sex-specific associations between systemic inflammation and physical activity behaviours. Longer time spent sedentary was also associated with higher levels of proinflammatory biomarkers in older women and lower level of antiinflammatory biomarkers in older men. Reallocating time spent in activities of lower intensities with higher intensities was associated with lower levels of pro-inflammatory biomarkers in older women. Overall, the findings of this thesis support efforts promoting physical activity at the expense of sedentary time in order to combat age-related systemic inflammation and metabolic risk in older adults.
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| 4. |
- Bredthauer, Andreas, 1977-
(författare)
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Tensionless Strings and Supersymmetric Sigma Models : Aspects of the Target Space Geometry
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, two aspects of string theory are discussed, tensionless strings and supersymmetric sigma models.The equivalent to a massless particle in string theory is a tensionless string. Even almost 30 years after it was first mentioned, it is still quite poorly understood. We discuss how tensionless strings give rise to exact solutions to supergravity and solve closed tensionless string theory in the ten dimensional maximally supersymmetric plane wave background, a contraction of AdS(5)xS(5) where tensionless strings are of great interest due to their proposed relation to higher spin gauge theory via the AdS/CFT correspondence.For a sigma model, the amount of supersymmetry on its worldsheet restricts the geometry of the target space. For N=(2,2) supersymmetry, for example, the target space has to be bi-hermitian. Recently, with generalized complex geometry, a new mathematical framework was developed that is especially suited to discuss the target space geometry of sigma models in a Hamiltonian formulation. Bi-hermitian geometry is so-called generalized Kähler geometry but the relation is involved. We discuss various amounts of supersymmetry in phase space and show that this relation can be established by considering the equivalence between the Hamilton and Lagrange formulation of the sigma model. In the study of generalized supersymmetric sigma models, we find objects that favor a geometrical interpretation beyond generalized complex geometry.
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| 5. |
- Eckert, Andreas, 1984-
(författare)
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Contributing to develop contributions : a metaphor for teaching in the reform mathematics classroom
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis aims at contributing to the theoretical research discourse on teaching mathematics. More precise, to explore a teacher’s role and actions while negotiating meaning of mathematical objects in discursive transformative practices in mathematics. The focus is to highlight the teacher as an active contributor to the classroom mathematical discourse, having an important role in shaping the mathematics. At the same time, the teacher is acknowledged as an individual who learns and develops as a lesson and semester progress.Three research papers illustrate the state, at that time, of an inductive analysis of three teachers, teaching a series of lessons based on probability theory at two Swedish primary schools. The teachers worked together with the students to explore an unknown sample space, made up out of an opaque bottle with coloured marbles within that showed one marble at each turn of the bottle. They had to construct mathematical tools together to help them solve the mystery. The analysis focused on teacher–student interactions during this exploration, revealing complex connections in the process of teaching.The three papers presented the development of a theoretical framework named Contributing to Develop Contributions (CDC). The frameworks’ fundamental idea is that teachers learn as they teach, using the teaching metaphor learning to develop learning. That metaphor was developed, in light of the ongoing empirical analysis, into CDC by drawing on a theoretical idea that learning can be viewed as contributing to the collaborative meaning making in the classroom. Teaching and teacher learning are described and understood as reflexive processes in relation to in-the-moment teacher-student interaction.Contributing to develop contributions consists of three different ways of contributing. The analytical categories illustrate how students’ opportunities to contribute to the negotiation of mathematical meaning are closely linked to teachers’ different ways of contributing. The different ways are Contributing one’s own interpretations of mathematical objects, Contributing with others’ interpretations of mathematical objects, and Contributing by eliciting contributions. Each way of contributing was found to have the attributes Transparency, Role-taking and Authority. Together, these six categories show teacher– student interaction as a complex dynamical system where they draw on each other and together negotiate meaning of mathematical objects in the classroom.This thesis reveals how the teaching process can be viewed in terms of learning on different levels. Learning as thought of in terms of contributing to the negotiation of meaning in the moment-to-moment interaction in the classroom. By contributing you influence the collective’s understanding as well as your own. A teacher exercises and develops ways of contributing to the negotiation of meaning of mathematical objects, in order to develop students’ contributions. In a wider perspective, the analysis showed development over time in terms of transformation. The teachers were found to have transformed their understanding of classroom situations in light of the present interactions. Contributing to the negotiation of meaning in the classroom was understood as a process in such transformation, in the ever ongoing becoming of a mathematics teacher.
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| 6. |
- Edholm, Peter, 1977-
(författare)
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Muscle mass and physical function in ageing : the effects of physical activity and healthy diet
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ageing is associated with a gradual deterioration in physical function, accompanied by a decrease in muscle mass, leading to loss of independency. In this respect, physical activity and healthy diet represent key lifestyle factors with potential to delay onset of age-related physical disability. The overall aim of the present thesis was to explore the effects of physical activity behaviours in general and resistance training (RT) in particular, with or without addition of a healthy diet (HD), on muscle mass and physical function in older community-dwelling women. A main finding was that physical activity of at least moderate intensity at old age infers beneficial effects on physical function, even in individuals with a previously sedentary lifestyle. Additionally, engagement in exercise-related activities during middleage years is linked to better physical function and higher muscle massat old age, regardless of present physical activity level. This thesis further highlights that in older women RT combined with HD rich in omega-3 polyunsaturated fatty acids elicits significant gains in muscle mass, whereas no corresponding gain was induced by RT alone. Likewise, larger improvements in muscle strength and physical function were evident in response to combined effects by RT and HD compared to RT alone. Taken together, findings from this thesis support public health efforts aiming to promote physical activity of at least moderate intensity together with a healthy diet rich in omega-3 polyunsaturated fatty acids in order to combat age-related decline in muscle mass and physical function.
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| 7. |
- Höglund, Andreas, 1980-
(författare)
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Regulation of DNA damage responses by the Myc oncogene : implications for future anti-cancer therapies
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Myc is a transcription factor frequently found deregulated in human cancer. Cells with deregulated expression of Myc carry a selective advantage against its neighbours due to the fact that Myc-mediated transcription governs crucial cellular events such as proliferation and growth. In addition, Myc has been implicated in several other aspects of tumour biology like cellular immortality, the formation of new blood vessels and the colonization of distant tissues through the process of metastasis. Therapy aimed at disrupting essential pathways regulated by Myc is important because of the many different types of cancers that depend on continued signalling along these pathways. This thesis describes new treatment opportunities for cancers with a high Myc signature. In Paper Ι, we describe a new role for the DNA methyltransferase inhibitor Decitabine in the treatment of Myc transformed tumours cells. We show that the therapeutic potential of Decitabine in the treatment of Burkitt Lymphoma relies not only on its ability to cause reactivation of silenced genes such as pro-apoptotic PUMA, but also on the DNA damage that this drug induces. In vivo, Decitabine delays disease progression of transplanted lymphoma cells. In Paper ΙΙ, we identify the DNA damage checkpoint kinase Chk1 as a therapeutic target in Myc overexpressing cancers. We show that targeting Chk1 with shRNA or with a novel small molecule inhibitor cause a delay in disease progression of transplanted lymphoma cells in vivo. In Paper ΙΙΙ, the Chk1-related kinase Chk2 is evaluated as a therapeutic target in Myc overexpressing cancers. Myc overexpressing cells are not dependent on Chk2 but we show that Chk2 abrogation using shRNA causes polyploidization and protection against DNA damage. However, Chk2-targeted therapy elicits a synergistic lethal response in combination with inhibition of the DNA repair associated protein PARP. In conclusion, this thesis shows the potential of targeting the DNA damage machinery and the functional hubs important for maintenance of genomic stability in tumours with a deregulated expression of Myc.
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| 8. |
- Knutsson, Sofie, 1983-
(författare)
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Towards Mosquitocides for Prevention of Vector-Borne Infectious Diseases : discovery and Development of Acetylcholinesterase 1 Inhibitors
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diseases such as malaria and dengue impose great economic burdens and are a serious threat to public health, with young children being among the worst affected. These diseases are transmitted by mosquitoes, also called disease vectors, which are able to transmit both parasitic and viral infections. One of the most important strategies in the battle against mosquito-borne diseases is vector control by insecticides and the goal is to prevent people from being bitten by mosquitoes. Today’s vector control methods are seriously threatened by the development and spread of insecticide-resistant mosquitos warranting the search for new insecticides. This thesis has investigated the possibilities of vector control using non-covalent inhibitors targeting acetylcholinesterase (AChE); an essential enzyme present in mosquitoes as well as in humans and other mammals. A key requirement for such compounds to be considered safe and suitable for development into new public health insecticides is selectivity towards the mosquito enzyme AChE1. The work presented here is focused on AChE1 from the disease transmitting mosquitoes Anopheles gambiae (AgAChE1) and Aedes aegypti (AaAChE1), and their human (hAChE) and mouse (mAChE) counterparts. By taking a medicinal chemistry approach and utilizing high throughput screening (HTS), new chemical starting points have been identified. Analysis of the combined results of three different HTS campaigns targeting AgAChE1, AaAChE1, and hAChE allowed the identification of several mosquito-selective inhibitors and a number of compound classes were selected for further development. These compounds are non-covalent inhibitors of AChE1 and thereby work via a different mechanism compared to current anti-cholinergic insecticides, whose activity is the result of a covalent modification of the enzyme. The potency and selectivity of two compound classes have been explored in depth using a combination of different tools including design, organic synthesis, biochemical assays, protein X-ray crystallography and homology modeling. Several potent inhibitors with promising selectivity for the mosquito enzymes have been identified and the insecticidal activity of one new compound has been confirmed by in vivo experiments on mosquitoes. The results presented here contribute to the field of public health insecticide discovery by demonstrating the potential of selectively targeting mosquito AChE1 using non-covalent inhibitors. Further, the presented compounds can be used as tools to study mechanisms important in insecticide development, such as exoskeleton penetration and other ADME processes in mosquitoes.
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| 9. |
- Markkanen, Peter, 1964-
(författare)
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Representationer, visualisering och resonemang i geometri : Praktiknära studier i digitala lärmiljöer
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this dissertation was to gain a deeper understanding of how teaching in digital environments can be designed to give students opportunities to develop knowledge in two- and three-dimensional geometry. The dissertation consists of two sub-studies, the first using an ethnographic approach in which the researcher followed a teacher's teaching in a digital environment, in a Grade 9 class for a period of five weeks. In the first study, learning was defined based on reification theory, which describes that the understanding of mathematical concepts develops from operational to structural understanding. Data were collected through video-assisted observations, interviews and student tests. This material was analyzed with a focus on the ways the teacher used the digital tools to create mathematical situations that offered students opportunities to work with different representations and mathematical concepts. In the second study, characterized as educational design research,t he researcher along with two teachers designed teaching in two classes in Grades 8 and 9. The focus in this second study was shifted to how geometry teaching in digital environments can be designed to offer students the opportunity to develop their understanding of, and ways of interpreting, geometric figures. For support in designing lessons, Brousseau's theory of didactical situations, based on a constructivist approach to learning, was adopted. Data were collected through video-assisted observations and screen recordings of students´ work. This material was analyzed in two steps. First, the focus was on how students worked with the figures in relation to the assumptions made in the design. Thereafter, the attention was on properties of the designed environment that were considered to affect the students and to lead to changes in how they interpreted and used the figures when working with geometric tasks. The study resulted in five design principles that can serve as a guide for designing teaching in digital environments. Thus, taken together, the dissertation´s two sub-studies show that using digital tools in teaching gives the teacher not only more didactic variables to work with when creating lessons, but also, based on the needs that arise in teaching, more tools for shedding light on what some students may have difficulty detecting. Furthermore, the results show that digital tools can help in the creation of environments that stimulate students' way of examining, testing and reasoning about geometric figures and their properties, which are seen as important prerequisites for developing good knowledge in the field.
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| 10. |
- Montiel Rojas, Diego, 1984-
(författare)
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Diet and sarcopenia risk in community-dwelling older European adults
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The age-related decline in muscle strength and muscle mass can lead to sarcopenia with higher risk of falls, disability, and loss of independence. In this context, healthy dietary habits have the potential to delay onset of physical limitations, thereby promoting healthy ageing. The overall aim of the thesis was to investigate the role of dietary habits on indicators ofmuscle health in a sample of community-dwelling older European men and women. The studies were performed within the frame of the NU-AGE project, a multi-centre study aiming to determine the impact of dietary habits on age-related functional decline. Studies I-III were based on crosssectional analyses, whereas study IV was a randomised controlled trial (RCT). In summary, Study I highlighted the independent roles of dietary protein amount and quality for muscle health in older adults. A positive linear dose-response relationship existed between protein intake and muscle health, with increased intake of plant-based proteins to the detriment of animal-based proteins was associated with reduced sarcopenia risk. Study II revealed that increased poly-unsaturated fatty acids intake to the detriment of saturated fatty acids was associated with lower sarcopenia risk in older adults with a dietary protein intake below 1.1 g/kg of body weight. In Study III, beneficial links between dietary fibre intake and muscle mass were observed in older European adults. In Study IV, a one-year RCT promoting adherence to a Mediterranean-style diet did not result in significant changes in muscle strength or mass. In conclusion, the present dissertation emphasised the important potential of macronutrient amount and quality in the prevention of age-related loss of muscle strength and muscle mass. However, future experimental studies are warranted to clarify the impact of whole-diet approaches, such as the Mediterranean diet, on the maintenance of muscle health in older adults.
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