| 1. |
- Jacobsson, Amanda, et al.
(författare)
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”Ambulanssjukvården behöver genomgripande förändringar”
- 2021
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Ingår i: Dagens Medicin. - : Dagens Medicin. - 1402-1943. ; :2021-06-23
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Debattörer från Ambulance health research network vill se en nationell ledningsstruktur, ökad evidens för vården, akademisk kompetens i ledningsfunktioner samt en nationell utbildnings- och kompetensstandard.
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| 2. |
- Johansson, Anders, 1968-
(författare)
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Search for Biomarkers in ALS and Parkinson's Disease : Positron Emission Tomography and Cerebrospinal Fluid Studies
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New biomarkers are needed to improve knowledge about pathophysiology, in order to provide earlier correct diagnosis and to follow disease progression of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). The aim of this thesis was to find new biomarkers for these diseases. First, increased serum levels and unchanged levels in postmortal spinal cord of vascular endothelial growth factor (VEGF) were demonstrated. VEGF was not detected in cerebrospinal fluid (CSF) in ALS. Second, increased levels of fibroblast growth factor 2 were found in the CSF and serum of ALS patients. Both studies used enzyme-linked immunoassays. Third, a proteomics method for CSF analysis was explored, based on tryptic digestion and subsequent separation and detection of the peptides by on-line liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. ALS-specific patterns were observed. Four out of five samples were correctly assigned, but no single protein biomarker could be identified. Fourth, [11C](L)-deprenyl-D2 (DED) positron emission tomography (PET) demonstrated increased retention in the pons and white matter in ALS. DED binds to monoamino oxidase B, which in the brain is primarily located in astrocytes. Thus evidence was provided that astrocytosis may be detected in vivo in ALS. Fifth, normal [11C]-PIB binding in five nondemented patients with PD was reported, in contrast to previous findings of increased retention in Alzheimer's disease reflecting amyloid aggregation. Finally, the combined use of fluorodeoxyglucose and L-[β 11C]-DOPA PET for the differential diagnosis of parkinsonian syndromes was evaluated. PET provided support for the clinical diagnosis in 62 out of 75 patients, and served to exclude suspected diagnoses in another five patients.
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| 3. |
- Persson, Anita M., 1975-
(författare)
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Evaluation of a Miniaturized Rotating Disk Apparatus for In Vitro Dissolution Rate Measurements in Aqueous Media : Correlation of In Vitro Dissolution Rate with Apparent Solubility
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to evaluate a newly designed and constructed miniaturized rotating disk apparatus for in vitro dissolution rate measurements of different drug substances from all of the classes in the Biopharmaceutical Classification System (BCS). The new equipment is based on a low volume flow-through cell of Plexiglas, a gold plated magnetic bar and a special designed press. The disk of drug substance (approx. 5 mg) is placed eccentrically in the bar. Rotation speeds were set with a graded magnetic stirrer. An external HPLC pump delivered a continuous flow of aqueous medium to the flow-through cell during dissolution testing. A reversed phase high-performance liquid chromatography system using diode array detection (RP-HPLC-DAD) was coupled online to the new equipment. The injections from the miniaturized rotating disk outlet into the quantifying HPLC system were controlled by a six-position switching valve. The injection volumes from the valve and the autosampler, used for the external standards, were statistically evaluated to match each other volumetrically. No analyses were longer than three minutes, using isocratic mode. A traditional USP rotating disk apparatus was used as a reference system and the two instruments were shown to be statistically dissimilar in the numerical dissolution rate values probably due to different hydrodynamics, but had approximately the same precision/repeatability. When correlating the logarithmic values of the in vitro dissolution rate (G) with the apparent solubility (S), using shake-flask methodology in the solubility studies, the two apparatuses gave the same correlation patterns. Further correlation studies were done where the media components were altered by the use of different buffer species or additives into the buffers, such as inorganic salts. Chemometric tools, e.g. orthogonal partial least squares (OPLS), were used to better evaluate the most influential factors for G and S in different media. The most significant factor for a model basic drug substance (terfenadine) was pH, followed by the ionic strength (I) and added sodium chloride in one of the media. However, the surfactants in the Fasted State Simulated Intestinal Fluid (FaSSIF-V2) were found to be insignificant for G and S in this study (using a 95% confidence interval). The new miniaturized apparatus is a promising prototype for in vitro dissolution rate measurements both for early screening purposes and in dissolution testing during drug development, but needs further instrumental improvements.
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| 4. |
- Wang, Chunliang, 1980-
(författare)
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Computer Assisted Coronary CT Angiography Analysis : Disease-centered Software Development
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The substantial advances of coronary CTA have resulted in a boost of use of this new technique in the last several years, which brings a big challenge to radiologists by the increasing number of exams and the large amount of data for each patient. The main goal of this study was to develop a computer tool to facilitate coronary CTA analysis by combining knowledge of medicine and image processing.Firstly, a competing fuzzy connectedness tree algorithm was developed to segment the coronary arteries and extract centerlines for each branch. The new algorithm, which is an extension of the “virtual contrast injection” method, preserves the low density soft tissue around the coronary, which reduces the possibility of introducing false positive stenoses during segmentation.Secondly, this algorithm was implemented in open source software in which multiple visualization techniques were integrated into an intuitive user interface to facilitate user interaction and provide good over¬views of the processing results. Considerable efforts were put on optimizing the computa¬tional speed of the algorithm to meet the clinical requirements.Thirdly, an automatic seeding method, that can automatically remove rib cage and recognize the aortic root, was introduced into the interactive segmentation workflow to further minimize the requirement of user interactivity during post-processing. The automatic procedure is carried out right after the images are received, which saves users time after they open the data. Vessel enhance¬ment and quantitative 2D vessel contour analysis are also included in this new version of the software. In our preliminary experience, visually accurate segmentation results of major branches have been achieved in 74 cases (42 cases reported in paper II and 32 cases in paper III) using our software with limited user interaction. On 128 branches of 32 patients, the average overlap between the centerline created in our software and the manually created reference standard was 96.0%. The average distance between them was 0.38 mm, lower than the mean voxel size. The automatic procedure ran for 3-5 min as a single-thread application in the background. Interactive processing took 3 min in average with the latest version of software. In conclusion, the presented software provides fast and automatic coron¬ary artery segmentation and visualization. The accuracy of the centerline tracking was found to be acceptable when compared to manually created centerlines.
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| 5. |
- Brüde Sundin, Josefin, 1975-
(författare)
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En riktig rektor : Om ledarskap, genus och skolkulturer
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of the study is to show, from an ethnographic point of view, the what, why and how of events in the daily life of the principals studied. The ambition is to try to understand the meaning of being a principal and the complex situation in which they op-erate. Some questions raised are: What do the principals’ working days look like? What constitutes the foundations of school leadership? What characterizes the context (the cul-tures) in which they work? Has gender any significance for school leadership?Earlier knowledge about leadership is mainly based on studies of male leaders, and or-ganizations are often considered as gender neutral. These circumstances make it urgent to study leadership from a gender perspective. Using an explorative, ethnographic approach with participant observations and recorded interviews seven principals were studied. Most of the data was collected during one and a half years of fieldwork, where the work of one female principal was observed.The result shows that leadership is a complex phenomenon. Relationships are seen as an essential aspect, and most of the daily work is accomplished through meetings and conver-sations with other people. The study illuminates how “a real principal” is constructed through relationships between many different individuals and groups. In this variety of sub-cultures different values and norms of behaviour are found. Schools can thus be regarded as multicultural organizations. Daily the principal has to try to understand, be aware of, and handle this cultural diversity. Partly as a consequence of this, emotions are constantly pre-sent in principals’ daily work. Principals have to deal with their own feelings as well as those of others. Contours of a gender contract are outlined, where cultural understandings of women and men become evident, and which the principals have to relate to.
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| 6. |
- De Geer, Jakob, 1970-
(författare)
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On the use of computed tomography in cardiac imaging
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCardiac Computed Tomography Angiography (CCTA) is becoming increasingly useful in the work‐up of coronary artery disease (CAD). Several potential methods for increasing the diagnostic yield of cardiac CT are available.Purpose Study I: To investigate whether the use of a 2‐D, non‐linear adaptive noise reduction filter can improve CCTA image quality.Study II: To evaluate the variation in adenosine stress dynamic CT perfusion (CTP) blood flow as compared to stress 99mTc SPECT. Secondly, to compare the perfusion results from manual and automatic myocardial CTP segmentation.Study III: To evaluate the accuracy of non‐invasive, CCTA‐derived Fractional Flow Reserve (cFFR).Study IV: To evaluate the prognostic value of CCTA in terms of major adverse cardiac events (MACE).Materials and methodsStudy I: Single images from 36 consecutive CCTA exams performed with two different dose levels were used. Image quality in full dose, low‐dose and noise‐reduced low‐dose images was graded using visual grading analysis. Image noise was measured.Study II: CTP and SPECT were performed in 17 patients, and the variation in per AHA‐segment blood flow was evaluated and compared. CTP results from manual and automated image segmentation were compared.Study III: CCTA datasets from 21 patients were processed using cFFR software and the results compared to the corresponding invasively measured FFR (invFFR).Study IV: 1205 consecutive patients with chest pain of unknown origin underwent CCTA. Baseline data and data on subsequent MACE were retrieved from relevant registries. Survival, hazard ratios and the three‐year incidence of cardiac events and readmissions were calculated.Results Study I: There was significant improvement in perceived image quality for all criteria when the filter was applied, and a significant decrease in image noise.Study II: The correlation coefficients for CTP vs. SPECT were 0.38 and 0.41 (p<0.001, for manual and automated segmentation respectively. Mean per patient CTP blood flow in normal segments varied between 94‐183 ml/100 ml tissue/min for manual segmentation, and 104‐196 ml/100 ml tissue/min for automated segmentation. The Spearman rank correlation coefficient for manual vs. automated segmentation CTP was ρ = 0.88 (p<0.001) and the Intraclass Correlation Coefficient (ICC) was 0.93 (p<0.001).Study III: The Spearman rank correlation coefficient for cFFR vs. invFFR was ρ = 0.77 (p<0.001) and the ICC was 0.73 (p<0.001). Sensitivity, specificity, positive predictive value and negative predictive value for significant stenosis (FFR<0.80, per vessel) were 0.83, 0.76, 0.56 and 0.93 respectively.Study IV: The hazard ratio for non‐obstructive CAD vs. normal coronary arteries was 5.13 (95% C.I 1.03‐25.43, p<0.05), and 151.40 (95% C.I 37.03‐619.08, p<0.001) for obstructive CAD vs. normal coronary arteries. The three‐year incidence of MACE was 1.1% for patients with normal vessels on CCTA, 2.5% for patients with non‐obstructive CAD and 42.7% for patients with obstructive CAD (p<0.001).Conclusions:Study I: Image quality and noise levels of low dose images were significantly improved with the filter, even though the improvement was small compared to the image quality of the corresponding diastolic full‐dose images.Study II: Correlation between dynamic CTP and SPECT was positive but weak. There were large variations in CTP blood flow in normal segments on SPECT, rendering the definition of an absolute cut‐off value for normal vs. ischemic myocardium difficult. Manual and automatic segmentation were equally useful.Study III: The correlation between cFFR and invFFR was good, indicating that noninvasively estimated cFFR performs on a similar level as invasively measure FFR. Study IV: The long‐term risk for MACE was very low in patients without obstructive CAD on CCTA, though there seemed to be a substantial increase in the risk for MACE even in patients with non‐obstructive CAD as compared to normal coronary arteries. In addition, even patients with normal coronary arteries or non‐obstructive CAD continued to have a substantial number of readmissions for chest pain or angina pectoris.
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| 7. |
- Ekblom Bak, Elin, 1981-, et al.
(författare)
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Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study
- 2022
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880
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Tidskriftsartikel (refereegranskat)abstract
- The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
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| 8. |
- Fraser, Magdalena
(författare)
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People of the Dolmens and Stone Cists : An archaeogenetic Investigation of Megalithic Graves from the Neolithic Period on Gotland
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The study of ancient genomics of pre-historic human remains has in recent years offered unprecedented knowledge regarding pre-historic migration and population structure on the European continent which has fundamentally altered the current views in the archaeological community. However, the merging of the two fields, archaeology and genetics, is still in its infancy and much work is still needed in order for these fields to integrate. In this thesis I explore how genetic analyses, in combination with contextual radiocarbon dating and isotopic analyses for diet and mobility can be used to investigate demographic events on a local and regional level. This is done through the investigation of people buried in five previously excavated megalithic tombs on the Island of Gotland dated to the Neolithic period. I present the genomic population structure and archaeological background for the pre-historic European reference data and show how this is used to investigate population continuity, demographic shifts, cultural duality, and admixture for local and regional contexts. I present new data and explore the Strontium-baseline for the Gotland biosphere which is used for the mobility analyses. I show that mitochondrial haplogroup data is especially useful in combination with isotopic data, and radiocarbon dating for investigation of demographic shifts on a larger scale. I also show that genomic data gives unique insights into the individuals’ life history which, together with the established demographic background allows for fine scale investigation of population demographic events within and between different archaeological contexts. Finally I show that the different Neolithic contexts on Gotland to a large extent involves immigration of new groups to the island, and that the contextual breaks seen in the archaeological record during the Neolithic period are connected with cultural and population demographic shifts. This dissertation demonstrates that genomic analyses, in combination with archaeology and isotopic analyses, as well as contextual osteological analyses and radiocarbon dating, present unique insights into the life history of the actual people who lived the lives we try to understand.
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| 9. |
- Fuchs, Alexander, 1985-
(författare)
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Assessment of predicting blood flow and atherosclerosis in the aorta and renal arteries
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular diseases (CVD) are the most common cause of death in large parts of the world. Atherosclerosis (AS) has a major part in most CVDs. AS is a slowly developingdisease which is dependent on multiple factors such as genetics and life style (food, smoking, and physical activities). AS is primarily a disease of the arterial wall and develops preferentially at certain locations (such as arterial branches and in certain vessels like thecoronary arteries). The close relation between AS sites and blood flow has been well established over the years. However, due to multi-factorial causes, there exist no early prognostic tools for identifying individuals that should be treated prophylactically or followed up. The underlying hypothesis of this thesis was to determine if it is possible to use bloodflow simulations of patient-specific cases in order to identify individuals with risk for developing AS. CT scans from patients with renal artery stenosis (RAS) were used to get the affected vessels geometry. Blood flow in original and “reconstructed” arteries were simulated. Commonly used wall shear stress (WSS) related indicators of AS were studied to assess their use as risk indicators for developing AS. Divergent results indicated urgent need to assess the impact ofsimulation related factors on results. Altogether, blood flow in the following vessels was studied: The whole aorta with branches from the aortic arch and the abdominal aorta, abdominal aorta as well as the renal arteries, and separately the thoracic aorta with the three main branching arteries from the aortic arch. The impact of geometrical reconstruction, employed boundary conditions (BCs), effects of flow-rate, heart-rate and models of blood viscosity as function of local hematocrit (red blood cell, RBC, concentration) and shear-rate were studied in some detail. In addition to common WSS-related indicators, we suggested the use of endothelial activation models as a further risk indicator. The simulations data was used to extract not only the WSS-related data but also the impact of flow-rate on the extent of retrograde flow in the aorta and close to its walls. The formation of helical motion and flow instabilities (which at high flow- and heart-rate lead to turbulence) was also considered.Results:A large number of simulations (more than 100) were carried out. These simulations assessed the use of flow-rate specified BCs, pressure based BCs or so called windkessel (WK) outlet BCs that simulate effects of peripheral arterial compliance. The results showed high sensitivity of the flow to BCs. For example, the deceleration phase of the flow-rate is more prone to flow instabilities (as also expressed in terms of multiple inflection points in the streamwise velocity profile) as well as leading to retrograde flow. In contrast, the acceleration phase leads to uni-directional and more stable flow. As WSS unsteadiness was found to be pro-AS, it was important to assess the effect flow-rate deceleration, under physiological and pathological conditions. Peaks of retrograde flow occur at local temporal minima in flow-rate. WK BCs require ad-hoc adjusted parameters and are therefore useful only when fully patient specific (i.e. all information is valid for a particular patient at a particular point of time) data is available. Helical flows which are considered as atheroprotective, are formed naturally, depending primarily on the geometry (due to the bends in the thoracic aorta). Helical flow was also observed in the major aortic branches. The helical motion is weaker during flow deceleration and diastole when it may locally also change direction. Most common existing blood viscosity models are based on hematocrit and shear-rate. These models show strong variation of blood (mixture) viscosity. With strong shear-rate blood viscosity is lowest and is almost constant. The impact of blood viscosity in terms of dissipation is counter balanced by the shear-rate; At low shear-rate the blood has larger viscosity and at high shear-rate it is the opposite. This effect and due to the temporal variations in the local flow conditions the effect of blood rheology on the WSS indicators is weak. Tracking of blood components and clot-models shows that the retrograde motion and the flow near branches may have so strong curvature that centrifugal force can become important. This effect may lead to the transport of a thrombus from the descending aorta back to the branches of the aortic arch and could cause embolic stroke. The latter results confirm clinical observation of the risk of stroke due to transport of emboli from the proximal part of the descending aorta upstream to the vessels branching from the aortic arch and which lead blood to the brain.Conclusions:The main reasons for not being able to propose an early predictive tool for future developmentof AS are four-folded:i. At present, the mechanisms behind AS are not adequately understood to enable to define aset of parameters that are sensitive and specific enough to be predictive of its development.ii. The lack of accurate patient-specific data (BC:s) over the whole physiological “envelop”allows only limited number of flow simulations which may not be adequate for patientspecificpredictive purposes.iii. The shortcomings of current models with respect to material properties of blood andarterial walls (for patient-specific space- and time-variations) are lacking.iv. There is a need for better simulation data processing, i.e. tools that enable deducinggeneral predictive atherosclerotic parameters from a limited number of simulations, throughe.g. extending reduced modeling and/or deep learning.The results do show, however, that blood flow simulations may produce very useful data thatenhances understanding of clinically observed processes such as explaining helical- andretrograde flows and the transport of blood components and emboli in larger arteries.
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| 10. |
- Israelsson, Johan, et al.
(författare)
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Dyadic effects of type D personality and perceived control on health-related quality of life in cardiac arrest survivors and their spouses using the actor–partner interdependence model
- 2020
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Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 19:4, s. 351-358
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a lack of knowledge about factors associated with health-related quality of life in cardiac arrest survivors and their spouses. In addition, survivors and spouses are likely to affect each other’s health-related quality of life.Aims: The aim was to investigate if a distressed personality and perceived control among cardiac arrest survivors and their spouses were associated with their own and their partner’s health-related quality of life.Methods: This dyadic cross-sectional study used the actor–partner interdependence model to analyse associations between a distressed personality (type D personality), perceived control (control attitudes scale), and health-related quality of life (EQ index and EQ visual analogue scale).Results: In total, 126 dyads were included in the study. Type D personality and perceived control in cardiac arrest survivors were associated with their own health-related quality of life. In their spouses, a significant association was found for type D personality but not for perceived control. In addition, type D personality and perceived control in survivors were associated with health-related quality of life in their spouses.Conclusions: Type D personality and perceived control are factors that might be considered during post cardiac arrest, because of the associations with health-related quality of life in survivors and spouses. More research is needed to test psychosocial interventions in the cardiac arrest population in order to improve health-related quality of life.
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