| 1. |
- Ericsson, Rolf
(författare)
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A Comparative Study of Head Development in Mexican Axolotl and Australian Lungfish: Cell Migration, Cell Fate and Morphogenesis
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of the vertebrate head is a complex process involving interactions between a multitude of cell types and tissues. This thesis describes the development of the cranial neural crest and of the visceral arch muscles in the head of two species. One, the Mexican axolotl (Ambystoma mexicanum), is a basal tetrapod, whereas the other, the Australian lungfish (Neoceratodus forsteri), belongs to the Dipnoi, the extant sister group of the Tetrapoda. The migration of neural crest cells, which form most of the bones and connective tissues in the head, and the morphogenesis of the jaw, was determined in the Mexican axolotl. It was shown that both the upper and lower jaws form from ventral condensations of neural crest cells in the mandibular arch. The dorsal condensation, earlier considered to give rise to the upper jaw, was shown to form the trabecula cranii.The normal spatio-temporal development of visceral arch muscles was investigated in both the Mexican axolotl and the Australian lungfish. In axolotl, the muscles tended to start forming almost simultaneously in all visceral arches at their future origins and extend towards their future insertions at the onset of muscle fibre formation. In lungfish, fibres formed simultaneously throughout most of each muscle anlage in the first and second visceral arch, but were delayed in the branchial arches. The anlagen were first observed at their future insertion, from which they developed towards future origins. To test the ability of neural crest cells to pattern the visceral arch muscles, migrating crest cells were extirpated from axolotl embryos, which resulted in a wide range of muscle malformations. In most cases, the muscles appeared in the right position but were small and extended in abnormal directions. This shows that neural crest cells are responsible not for the position of the muscles but for their correct anatomical pattern. Fate mapping showed that connective tissue surrounding myofibers is, at least partly, neural crest derived.In conclusion, the work presented in this thesis shows that although early development may map out the patterns of later development, the differences between axolotl and lungfish head development are not seen until during morphogenesis. Further investigation of morphogenesis is needed to explain the great variation of head morphology seen in vertebrates today.
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| 2. |
- 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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| 3. |
- Bornefalk Hermansson, Anna, 1971-
(författare)
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Resampling Evaluation of Signal Detection and Classification : With Special Reference to Breast Cancer, Computer-Aided Detection and the Free-Response Approach
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first part of this thesis is concerned with trend modelling of breast cancer mortality rates. By using an age-period-cohort model, the relative contributions of period and cohort effects are evaluated once the unquestionable existence of the age effect is controlled for. The result of such a modelling gives indications in the search for explanatory factors. While this type of modelling is usually performed with 5-year period intervals, the use of 1-year period data, as in Paper I, may be more appropriate.The main theme of the thesis is the evaluation of the ability to detect signals in x-ray images of breasts. Early detection is the most important tool to achieve a reduction in breast cancer mortality rates, and computer-aided detection systems can be an aid for the radiologist in the diagnosing process.The evaluation of computer-aided detection systems includes the estimation of distributions. One way of obtaining estimates of distributions when no assumptions are at hand is kernel density estimation, or the adaptive version thereof that smoothes to a greater extent in the tails of the distribution, thereby reducing spurious effects caused by outliers. The technique is described in the context of econometrics in Paper II and then applied together with the bootstrap in the breast cancer research area in Papers III-V.Here, estimates of the sampling distributions of different parameters are used in a new model for free-response receiver operating characteristic (FROC) curve analysis. Compared to earlier work in the field, this model benefits from the advantage of not assuming independence of detections in the images, and in particular, from the incorporation of the sampling distribution of the system's operating point.Confidence intervals obtained from the proposed model with different approaches with respect to the estimation of the distributions and the confidence interval extraction methods are compared in terms of coverage and length of the intervals by simulations of lifelike data.
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| 4. |
- Gabrielsson, Sebastian
(författare)
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A moral endeavour in a demoralizing context: Psychiatric inpatient care from the perspective of professional caregivers
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients in psychiatric care experience a need for and expect to develop interpersonal relationships with professional caregivers and to be respected and listened to. Despite demands for care to be person-centred and recovery-oriented, patients experience that psychiatric inpatient care fails to meet their expectations. Nursing research suggest that nurses aspire to engage with and meet the needs of patients, but that the strenuous reality of inpatient care prevents them from doing so. Exploring the content and context of psychiatric inpatient care from the perspective of professional caregivers might provide valuable insights regarding what caregivers do, and more importantly it can aid in understanding why they do what they do.This thesis aimed to explore the content and context of adult psychiatric inpatient care from the perspective of professional caregivers. This was achieved by clarifying the concept of person-centred care in the context of inpatient psychiatry, describing staff members’ reasoning on their choice of action and perceptions of interprofessional collaboration in challenging situations in inpatient psychiatric care settings, and exploring nurses’ experiences of good nursing practice in the specific context of inpatient psychiatry. A systematic review of the literature identified 34 scholarly papers that were analysed using evolutionary concept analysis. Focus group interviews were conducted with 26 professional caregivers and analysed using qualitative content analysis. Individual qualitative interviews were conducted with 12 skilled, relationship-oriented nurses and analysed using an interpretive descriptive approach to qualitative analysis.Reviewing the literature on person-centred care in inpatient psychiatry clarified how person-centred care is expected to result in quality care when interpersonal relationships are used to promote recovery. Professional caregivers’ reasoning on choice of action described different concerns in caregiver-patient interaction resulting in a focus on either meeting patients’ individual needs or solving staff members’ own problems. Describing professional caregivers’ perceptions of interprofessional collaboration suggested that they are being constrained by difficulties in collaborating with each other and a lack of interaction with patients. Exploring nurses’ experiences of good nursing practice revealed how circumstances in the clinical setting affect nurses’ ability to work through relationships. It is argued that these findings describe the workings of two opposing forces in psychiatric inpatient care. The concept of caring as a process forms the basis for discussing the content of care as a moral endeavour in which nurses strive to do good. The concept of demoralizing organizational processes is used to discuss the context of care as demoralizing and allowing for immoral actions.The main conclusions to be drawn are that, from a nursing perspective, nurses in psychiatric inpatient care need to focus on patients’ experiences and needs. For this they need sufficient resources and time to be present and develop relationships with patients.Nurses in psychiatric inpatient care also need to take personal responsibility for their professional practice. Attempts to transform psychiatric care in a person-centred direction must consider all of these aspects and their interrelatedness. Further research on psychiatric inpatient care is needed to understand more about how the content of care relates to the context of care.
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| 5. |
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| 6. |
- Olsson, Anki
(författare)
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Hemostatic function and inflammatory activation after weaning from cardio pulmonary bypass
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiopulmonary bypass (CPB) contributes to perioperative platelet dysfunction, increased fibrinolysis and impaired coagulation, which can have an impact on postoperative bleeding. During CPB the blood is exposed to foreign surfaces leading to activation of the coagulation system and a systemic inflammatory response with complement and leukocyte activation. Anticoagulation with heparin is used to prevent immediate blood clotting within the circuit. The heparin effect is reversed with protamine sulfate after weaning from CPB. Protamine has been suggested to impair platelet function in high doses although the mechanism is incompletely understood. Platelet dysfunction can promote bleeding which can necessitate transfusion and sometimes surgical re-exploration.After weaning from CPB the residual blood in the heart lung machine is usually retransfused to the patient in order to reduce the need for blood transfusion. The most common technique to transfuse residual blood is to collect the blood from the CPB circuit in an infusion bag (IB). An alternative way to re-transfuse the residual blood is by chasing it through the heart lung machine with Ringers solution, the Ringer chase technique (RC).The aim of this thesis was to examine a possible inhibitory effect of protamine on platelet aggregation. A second aim was to evaluate different techniques for retransfusion after weaning from CPB.Study I and II in this thesis are focused on the protamine effect on platelet aggregation and study III and IV on the quality of the blood in relation to the two different retransfusion techniques.In Study I we found that platelet aggregation evaluated by impedance aggregometry was reduced by approximately 50% after in vivo protamine administration. Protamine added in vitro also reduced platelet aggregation, by itself or in combination with heparin. Study II showed that protamine induces a marked but transient decrease in platelet aggregation already at a protamine-heparin ratio of 0.7:1, which also was sufficient to reverse the heparin anticoagulation as measured by activated clotting time (ACT). No further decrease was observed when additional protamine was given within three minutes. Platelet aggregation had begun to recover 20 minutes after protamine administration.In study III and IV we evaluated possible differences in quality of the retransfused residual blood from the heart-lung machine depending on if it is returned to the patient by the RC-technique or by an IB. Study III focused on biochemical markers of hemostasis, coagulation and fibrinolysis. Study IV concerns biochemical markers of inflammatory activity characterizing the inflammatory response during cardiac surgery with CPB including heparin binding protein (HBP) a new marker of neutrophil activation. CPB is associated with a marked systemic inflammatory response and levels of HBP indicates a pronounced neutrophil activation as part of a systemic inflammatory process. HBP levels during CPB was much higher than previously found during severe inflammatory conditions. We also concluded that the handling of the blood after weaning from CPB reduces platelet function, activates coagulation and fibrinolysis, increases hemolysis and the inflammatory response. Retransfusion of pump blood with the RC-technique was associated with better preserved platelet function, less hemolysis, less signs of activation of coagulation and fibrinolysis and less pronounced inflammatory activity than the commonly used IB technique. In the event of cell salvage technique not being feasible, we suggest that the RC technique is preferable to the IB technique but acknowledge that the clinical importance of this finding in terms of outcomes warrants further investigation
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| 7. |
- Olsson, Rolf, 1969-
(författare)
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MANAGING PROJECT UNCERTAINTY BY USING AN ENHANCED RISK MANAGEMENT PROCESS
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An increasing number of companies are focusing their efforts on project management. Project management is frequently used as an enabler for meeting an uncertain and turbulent environment. Consequently, the overall effectiveness of the project management process is essential for long-term profitability. The aim and final effects of project management are to predict the outcome, i.e. cost, time and quality. However, uncertainty is inherent in the objectives of the project itself, as we use assumptions and expectations in defining and realizing the outcome of the project. A project’s ability to identify and react to uncertainty will influence the outcome of the project. Presently, risk management processes exist in several forms and are often used to manage uncertainty. However, it is frequently argued in academia as well as for the practitioner that risk management does not live up to expected results. The overall objective of this research is to improve the process for managing risks and opportunities within a project organization. The research starts from the single project view, followed by the strategic link to business strategy by including the project portfolio management perspective. Finally, the research focuses on opportunities and the ability of a project to realize them. Thus, the research questions addressed concern how risk is conceived in a theoretical global context and how this would assist in developing a methodology for risk management in an international project organization. They also involve how risk management within a project portfolio could be conducted and its effectiveness measured. Finally, the research questions also address how the management of opportunities could be improved. This research includes the development of four methodologies, based on industrial need. A holistic approach with a systems perspective has been used in order to handle the complexity of the research task. Both empirical and theoretical material has been used for developing the proposed methodologies. The developed methodologies for project risk management and the measures of its effectiveness have been tested and improved over a five-year period within the complete case company. Subsequently, two of them were implemented. The developed methodologies show that the risk management process in a single project does not foster learning and is not directly applicable within a portfolio of projects. Furthermore, the risk management process is not able to address all types of uncertainty. The project manager is a major factor in an effective management of uncertainty. When identifying and managing opportunity, having the ability to create a holistic view, to oversee both customer expectations, and to communicate project related information are important factors. Furthermore, the implementation also showed that it is actually possible, through the consistent use of a risk management process, to develop a cultural behavior within an organization that is much more preventive and proactive than before.
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| 8. |
- Persson, Monika, 1979-
(författare)
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The dynamics of policy formation : making sense of feelings of public unsafety
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every policy problem has inherent value dimensions. It is on the basis of values that a state of affairs is perceived as undesirable, and thus acknowledged as a problem. This makes the process of defining and negotiating the meaning of a problem an essentially political process. Despite this, bureaucracy and expertise have a strong, if not increasing, influence over the formation of policy problems. An objectivist knowledge view predominates within the public managerial realm, which obscures the political dimension of problem formulation, while policy problems tend to be approached as a matter of efficiency.This thesis provides an account of mechanisms that shape and constrain the way a particular policy problem is understood and addressed. It analyses how policy actors make sense of particular problems, by drawing on different discourses (scientific, institutional, popular or media). The empirical case of this thesis is the formation of public safety policy in Sweden. The understanding of the problem of unsafety within Swedish policy is shown to be intrinsically related to the research field of fear of crime. The two are mutually dependent and exert an ideational path dependency. The ideational constraints on the understanding of unsafety are further affected by the institutional setting. It is argued that the appointed institutions and the emphasis on local level have a part in fostering individualist explanations and solutions,while obviating structural interpretations of the problem.The thesis finds that when governing complex policy problems there is a need to pay closer attention to how the problem is defined and how its meaning is constrained. It is crucial to make transparent the values inherent in definitions of problems as well as in research claims. By acknowledging the entwinement of policy and research the policy formation process may become characterized by greater reflexivity, and the possibility of resolving wicked problems may enlarge.
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| 9. |
- Westerberg, Marcus, 1990-
(författare)
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Prostate cancer incidence, treatment and mortality : Empirical longitudinal register-based studies and methods for handling missing data
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The diagnostic activity for prostate cancer has increased substantially in Sweden, primarily due to increased use of prostate-specific antigen (PSA) testing in asymptomatic men, and this has led to a large increase in diagnoses. There have also been changes in the diagnostic workup, guidelines, treatment strategies, and more effective treatments have been introduced in different phases of the disease. This thesis aims to increase the understanding of consequences of changes in diagnostic activity and treatment, with a focus on empirical studies, methodological development, and handling of missing data.In paper I, the survival of men with metastatic prostate cancer was investigated across calendar time periods by use of Kaplan-Meier analyses and Cox regression. The median survival from diagnosis increased with six months comparing men diagnosed 1998-2001 with men diagnosed 2010-2015, while median PSA decreased.In paper II, a discrete time multivariate longitudinal model was combined with a proxy for the unobserved level of diagnostic activity to produce prognoses of incidence and mortality. Simulations indicated that a higher diagnostic activity was associated with fewer men diagnosed with metastatic disease and fewer prostate cancer deaths.In paper III, we looked for clinical variables predictive of the survival of men with castration-resistant prostate cancer (CRPC). A new data base was created including longitudinal data on prescriptions of hormonal treatment, PSA, and cause of death. We found that PSA doubling time and PSA at time of CRCP were highly predictive and could be used for treatment decision.In paper IV, we estimated annual incidence of metastatic prostate cancer using different methods for handling missing data in metastatic status (M stage). Missing data in M stage was high and varied over calendar time and risk groups, yet each method indicated a downward trend in incidence. Although men with unknown metastatic status cannot be assumed to have nonmetastatic disease in general, this may be reasonable among those with tumour characteristics that indicate a low risk of metastases.In paper V, the estimation of multivariate longitudinal models was considered in a context where some events are observed on a coarser level (e.g. grouped) at some time points, causing gaps in the data. The likelihood function, score and observed information were derived under an independent coarsening mechanism. A simulation study was conducted comparing properties of several estimators including direct maximum likelihood and Monte Carlo Expectation Maximisation.
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