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- Dahlberg, Johan, 1988-
(författare)
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Genetic Cartography at Massively Parallel Scale
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Massively parallel sequencing (MPS) is revolutionizing genomics. In this work we use, refine, and develop new tools for the discipline.MPS has led to the discovery of multiple novel subtypes in Acute Lymphoblastic Leukemia (ALL). In Study I we screen for fusion genes in 134 pediatric ALL patients, including patients without an assigned subtype. In approximately 80% of these patients we detect novel or known fusion gene families, most of which display distinct methylation and expression patterns. This shows the potential for improvements in the clinical stratification of ALL. Large sample sizes are important to detect recurrent somatic variation. In Study II we investigate if a non-index overlapping pooling schema can be used to increase sample size and detect somatic variation. We designed a schema for 172 ALL samples and show that it is possible to use this method to call somatic variants.Around the globe there are many ongoing and completed genome projects. In Study III we sequenced the genome of 1000 Swedes to create a reference data set for the Swedish population. We identified more than 10 million variants that were not present in publicly available databases, highlighting the need for population-specific resources. Data, and the tools developed during this study, have been made publicly available as a resource for genomics in Sweden and abroad.The increased amount of sequencing data has created a greater need for automation. In Study IV we present Arteria, a computational automation system for sequencing core facilities. This system has been adopted by multiple facilities and has been used to analyze thousands of samples. In Study V we developed CheckQC, a program that provides automated quality control of Illumina sequencing runs. These tools make scaling up MPS less labour intensive, a key to unlocking the full future potential of genomics.The tools, and data presented here are a valuable contribution to the scientific community. Collectively they showcase the power of MPS and genomics to bring about new knowledge of human health and disease.
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| 2. |
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| 3. |
- Lundh, Torbjörn, 1965, et al.
(författare)
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Device and method for treating ruptured aneurysms
- 2014
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Patent (övrigt vetenskapligt/konstnärligt)abstract
- A stent device for treating an aneurysm is disclosed. The stent device comprises an expandable balloon with a channel extending through said balloon from one side to another, and a supporting stent connected to said balloon. In an operative disposition, when the expandable balloon is expanded, the supporting stent is arranged at least partly within said channel of said expandable balloon. Further, the supporting stent has walls which are permeable to blood. The stent device may be introduced and removed by endoscopic procedures, with a relatively simple procedure. Thus, the stent device is highly useable for fast and temporary treatment of ruptured aneurysms.
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| 4. |
- Nyholm, Tufve, et al.
(författare)
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MR and CT data with multiobserver delineations of organs in the pelvic areaPart of the Gold Atlas project
- 2018
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Ingår i: Med Phys. - : Wiley. - 0094-2405 .- 2473-4209. ; 45:3, s. 1295-1300
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Tidskriftsartikel (refereegranskat)abstract
- PurposeWe describe a public dataset with MR and CT images of patients performed in the same position with both multiobserver and expert consensus delineations of relevant organs in the male pelvic region. The purpose was to provide means for training and validation of segmentation algorithms and methods to convert MR to CT like data, i.e., so called synthetic CT (sCT). Acquisition and validation methodsT1- and T2-weighted MR images as well as CT data were collected for 19 patients at three different departments. Five experts delineated nine organs for each patient based on the T2-weighted MR images. An automatic method was used to fuse the delineations. Starting from each fused delineation, a consensus delineation was agreed upon by the five experts for each organ and patient. Segmentation overlap between user delineations with respect to the consensus delineations was measured to describe the spread of the collected data. Finally, an open-source software was used to create deformation vector fields describing the relation between MR and CT images to further increase the usability of the dataset. Data format and usage notesThe dataset has been made publically available to be used for academic purposes, and can be accessed from . Potential applicationsThe dataset provides a useful source for training and validation of segmentation algorithms as well as methods to convert MR to CT-like data (sCT). To give some examples: The T2-weighted MR images with their consensus delineations can directly be used as a template in an existing atlas-based segmentation engine; the expert delineations are useful to validate the performance of a segmentation algorithm as they provide a way to measure variability among users which can be compared with the result of an automatic segmentation; and the pairwise deformably registered MR and CT images can be a source for an atlas-based sCT algorithm or for validation of sCT algorithm. (c) 2018 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.
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| 5. |
- Ghirmai, Semhar, 1993, et al.
(författare)
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In vivo evaluation of electron mediators for the reduction of methemoglobin encapsulated in liposomes using electron energies produced by red blood cell glycolysis
- 2017
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Ingår i: Artificial Cells, Nanomedicine and Biotechnology. - : Informa UK Limited. - 2169-1401 .- 2169-141X. ; 46:7, s. 1364-1372
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Tidskriftsartikel (refereegranskat)abstract
- Earlier studies have clarified that NADH and NADPH, re-energized repeatedly by red blood cell (RBC) glycolysis, can be used in extracellular chemical reactions, where electron energies are extracted by electron mediators, such as methylene blue (MB). The electron mediators, which are reduced by NAD(P)H, permeate both the membranes of RBC and phospholipid bilayer of liposomes encapsulating haemoglobin (Hb-vesicles, HbV) and reduce autoxidized ferric methemoglobin (metHb) in HbV to ferrous Hb. Moreover, in vitro screening study clarified some other potential electron mediators with comparable capacity to reduce metHb. Given this background, eight of these compounds: MB, 1,9-dimethyl MB, azure A, azure B (AB), azure, toluidine blue, brilliant cresyl blue and toluylene blue, were evaluated in both in vitro and in vivostudies in this work. Compared with MB as a reference, in vitro experiments demonstrated that most compounds caused effective metHb reduction of HbV in the presence of RBC. However, in vivo experiments of bolus injection of autoxidized HbV to rats (10 mL HbV/kg body weight) followed by injection of the dye (1.53 mL/kg body weight, 2.6 mM) led to some differences from in vitro results. Effective metHb reduction was found for the combination of AB. To evaluate AB effectiveness further, a haemorrhagic shock and resuscitation model was used, where the rats were resuscitated with HbV. When the level of metHb increased to 50%, a dye solution was injected. Again, AB caused sufficient reduction of metHb. Through these in vivo experiments, this study clarified that AB is a suitable electron mediator to prolong the functional lifetime of HbV.
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| 6. |
- Shahgaldi, Kambiz, et al.
(författare)
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Three-dimensional echocardiography using single-heartbeat modality decreases variability in measuring left ventricular volumes and function in comparison to four-beat technique in atrial fibrillation
- 2010
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Ingår i: Cardiovascular Ultrasound. - : Springer Science and Business Media LLC. - 1476-7120. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Three dimensional echocardiography (3DE) approaches the accuracy of cardiac magnetic resonance in measuring left ventricular (LV) volumes and ejection fraction (EF). The multibeat modality in comparison to single-beat (SB) requires breath-hold technique and regular heart rhythm which could limit the use of this technique in patients with atrial fibrillation (AF) due to stitching artifact. The study aimed to investigate whether SB full volume 3DE acquisition reduces inter-and intraobserver variability in assessment of LV volumes and EF in comparison to four-beat (4B) ECG-gated full volume 3DE recording in patients with AF. Methods: A total of 78 patients were included in this study. Fifty-five with sinus rhythm (group A) and 23 having AF (group B). 4B and SB 3DE was performed in all patients. LV volumes and EF was determined by these two modalities and inter-and intraobserver variability was analyzed. Results: SB modality showed significantly lower inter-and intraobserver variability in group B in comparison to 4B when measuring LV volumes and EF, except for end-systolic volume (ESV) in intraobserver analysis. There were significant differences when calculating the LV volumes (p < 0.001) and EF (p < 0.05) with SB in comparison to 4B in group B. Conclusion: Single-beat three-dimensional full volume acquisition seems to be superior to four-beat ECG-gated acquisition in measuring left ventricular volumes and ejection fraction in patients having atrial fibrillation. The variability is significantly lower both for ejection fraction and left ventricular volumes.
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| 7. |
- Skattum, Lillemor
(författare)
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Clinical Complement Analysis—An Overview
- 2019
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Ingår i: Transfusion Medicine Reviews. - : Elsevier BV. - 0887-7963. ; 33:4, s. 207-216
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Forskningsöversikt (refereegranskat)abstract
- The complement system plays an important role in varying types of disease, ranging from inflammatory and autoimmune disorders to immune deficiency states. In addition, new settings have emerged where complement analysis is of interest to monitor complement-directed therapy and aid identification of transplant complications. Therefore, it is critical that clinical laboratories offer optimized and timely complement analysis. This review presents a comprehensive overview of the most important complement analysis methods that are currently used. It also points to some areas within complement diagnostics where development is needed, for example, regarding certain analytes for which practical methods suitable for the routine laboratory are lacking. Furthermore, it contains a more detailed discussion on complement autoantibody assessment. The list of analyses providing clinically valuable information includes analysis of complement function, quantification of individual complement components and complement activation fragments, identification of autoantibodies to complement, as well as genetic complement analyses. There is still a shortage of commercially available methods suitable for high-throughput screening of complement deficiency and for assessment of complement activation, but development is under way. There is also ongoing work within the complement community to improve standardization of measurements, and recently, an extensive quality assurance program has been initiated.
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| 8. |
- Urbansky, Anke, et al.
(författare)
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Rapid and effective enrichment of mononuclear cells from blood using acoustophoresis
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Effective separation methods for fractionating blood components are needed for numerous diagnostic and research applications. This paper presents the use of acoustophoresis, an ultrasound based microfluidic separation technology, for label-free, gentle and continuous separation of mononuclear cells (MNCs) from diluted whole blood. Red blood cells (RBCs) and MNCs behave similar in an acoustic standing wave field, compromising acoustic separation of MNC from RBC in standard buffer systems. However, by optimizing the buffer conditions and thereby changing the acoustophoretic mobility of the cells, we were able to enrich MNCs relative to RBCs by a factor of 2,800 with MNC recoveries up to 88%. The acoustophoretic microchip can perform cell separation at a processing rate of more than 1 × 105 cells/s, corresponding to 5 μl/min undiluted whole blood equivalent. Thus, acoustophoresis can be easily integrated with further down-stream applications such as flow cytometry, making it a superior alternative to existing MNC isolation techniques.
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| 9. |
- Kroon, Martin, et al.
(författare)
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A model for saccular cerebral aneurysm growth by collagen fibre remodelling
- 2007
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Ingår i: Journal of Theoretical Biology. - : Elsevier BV. - 0022-5193 .- 1095-8541. ; 247:4, s. 775-787
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Tidskriftsartikel (refereegranskat)abstract
- The first structural model for saccular cerebral aneurysm growth is proposed. It is assumed that the development of the aneurysm is accompanied by a loss of the media, and that only collagen fibres provide load-bearing capacity to the aneurysm wall. The aneurysm is modelled as an axisymmetric multi-layered membrane, exposed to an inflation pressure. Each layer is characterized by an orientation angle, which changes between different layers. The collagen fibres and fibroblasts within a specific layer are perfectly aligned. The growth and the morphological changes of the aneurysm are accomplished by the turnover of collagen. Fibroblasts are responsible for collagen production, and the related deformations are assumed to govern the collagen production rate. There are four key parameters in the model: a normalized pressure, the number of layers in the wall, an exponent in the collagen mass production rate law, and the pre-stretch under which the collagen is deposited. The influence of the model parameters on the aneurysmal response is investigated, and a stability analysis is performed. The model is able to predict clinical observations and mechanical test results, for example, in terms of predicted aneurysm size, shape, wall stress and wall thickness.
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