| 1. |
- Dahlberg, Johan, et al.
(author)
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Arteria : An automation system for a sequencing core facility
- 2019
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In: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 8:12
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Journal article (peer-reviewed)abstract
- Background: In recent years, nucleotide sequencing has become increasingly instrumental in both research and clinical settings. This has led to an explosive growth in sequencing data produced worldwide. As the amount of data increases, so does the need for automated solutions for data processing and analysis. The concept of workflows has gained favour in the bioinformatics community, but there is little in the scientific literature describing end-to-end automation systems. Arteria is an automation system that aims at providing a solution to the data-related operational challenges that face sequencing core facilities.Findings: Arteria is built on existing open source technologies, with a modular design allowing for a community-driven effort to create plug-and-play micro-services. In this article we describe the system, elaborate on the underlying conceptual framework, and present an example implementation. Arteria can be reduced to 3 conceptual levels: orchestration (using an event-based model of automation), process (the steps involved in processing sequencing data, modelled as workflows), and execution (using a series of RESTful micro-services). This creates a system that is both flexible and scalable. Arteria-based systems have been successfully deployed at 3 sequencing core facilities. The Arteria Project code, written largely in Python, is available as open source software, and more information can be found at https://arteria-project.github.io/.Conclusions: We describe the Arteria system and the underlying conceptual framework, demonstrating how this model can be used to automate data handling and analysis in the context of a sequencing core facility.
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| 2. |
- La Fleur, Linnea, et al.
(author)
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Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11
- 2019
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In: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 130, s. 50-58
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Non-small cell lung cancer (NSCLC) is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients, as well as significant differences in populations across the world with regard to mutation spectra and mutation frequencies. Here we aim to describe mutational patterns and linked clinical parameters in a population-based NSCLC cohort.MATERIALS AND METHODS: Using targeted resequencing the mutational status of 82 genes was evaluated in a consecutive Swedish surgical NSCLC cohort, consisting of 352 patient samples from either fresh frozen or formalin fixed paraffin embedded (FFPE) tissues. The panel covers all exons of the 82 genes and utilizes reduced target fragment length and two-strand capture making it compatible with degraded FFPE samples.RESULTS: We obtained a uniform sequencing coverage and mutation load across the fresh frozen and FFPE samples by adaption of sequencing depth and bioinformatic pipeline, thereby avoiding a technical bias between these two sample types. At large, the mutation frequencies resembled the frequencies seen in other western populations, except for a high frequency of KRAS hotspot mutations (43%) in adenocarcinoma patients. Worse overall survival was observed for adenocarcinoma patients with a mutation in either TP53, STK11 or SMARCA4. In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration. Similar results were seen in the analysis of publicly available data from the cBioPortal. In squamous cell carcinoma a worse prognosis could be observed for patients with MLL2 mutations, while CSMD3 mutations were linked to a better prognosis.CONCLUSION: Here we have evaluated the mutational status of a NSCLC cohort. We could not confirm any survival impact of isolated driver mutations. Instead, concurrent mutations in TP53 and STK11 were shown to confer poor survival in the KRAS-positive adenocarcinoma subgroup.
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| 3. |
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| 4. |
- Ander, S J, et al.
(author)
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Growth and function of human parathyroid tissue transplanted to athymic mice.
- 1997
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In: Journal of endocrinological investigation. - 0391-4097. ; 20:11, s. 640-7
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Journal article (peer-reviewed)abstract
- The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands.
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| 5. |
- Ander, S J, et al.
(author)
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Revascularisation of human parathyroid tissue transplanted to athymic mice.
- 1997
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In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - 0903-4641. ; 105:12, s. 931-40
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Journal article (peer-reviewed)abstract
- The revascularisation process of transplanted human normal, hyperplastic and adenomatous parathyroid tissue was analysed at 2 and 4 days and 1, 2, 4, 7 and 12 weeks after transplantation to athymic mice. The transplants were examined by light and electron microscopy, immunohistochemistry and autoradiography. Vessels were detected by monoclonal antibodies specific for mouse and human endothelial cells. Immunohistochemistry demonstrated ingrowth of vessels from the host into the transplant and at one week numerous capillary sprouts were observed in the peripheral parts of the transplants. During the first week, peak levels of proliferation (labelling index) were observed in endothelial cells and capsular fibroblasts, and the proliferative capacity of endothelial cells was most pronounced in adenoma transplants. Fenestrated capillaries were observed in hyperplastic and adenomatous transplants, but not in transplants of normal tissue. In conclusion, revascularisation of transplanted human parathyroid tissue is enabled by ingrowth of vessels from the host into the transplant. The proliferative capacity of endothelial cells is higher and the process of maturation is faster in hyperplastic and adenomatous tissue compared to normal tissue.
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| 6. |
- Forsblad-D’Elia, Helena, et al.
(author)
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Biomechanical properties of common carotid arteries assessed by circumferential 2D strain and β stiffness index in patients with ankylosing spondylitis
- 2021
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In: Journal of Rheumatology. - 0315-162X. ; 48:3, s. 352-360
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Journal article (peer-reviewed)abstract
- Objective. Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate β stiffness index (indicating arterial stiffness) and, a more recently developed technique, 2-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to (1) compare with age- and sex-matched controls, and (2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in patients with AS. Methods. In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.3 ± 11.2 years, 102 (68.5%) men, and 146 (98%) HLA-B27–positive, were examined. Bilateral CCA were examined for circumferential 2D strain and β stiffness index. A subgroup of 46 patients was compared with 46 age- and sex-matched controls, both groups without hypertensive disease, diabetes, myocardial infarction, or stroke. Results. Mean bilateral circumferential 2D strain was lower in AS patients compared with controls (7.9 ± 2.6% vs 10.3 ± 1.9%, P < 0.001), whereas mean bilateral β stiffness index was higher (13.1 ± 1.7 mmHg/mm vs 12.3 ± 1.3 mmHg/mm, P = 0.02). In multivariable linear regression analyses, strain was associated with age, erythrocyte sedimentation rate, history of anterior uveitis, and treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARD) and/or biological DMARD (R2 0.33), while stiffness was associated with age (R2 0.19). Conclusion. Both CCA circumferential 2D strain and β stiffness index differed between patients with AS and controls. Strain was associated with AS-related factors and age, whereas only age was associated with stiffness, suggesting that the obtained results reflect different pathogenic vascular processes.
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| 7. |
- Forsblad-d'Elia, Helena, et al.
(author)
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Biomechanical properties of common carotid arteries assessed by circumferential two-dimensional strain and β stiffness index in patients with ankylosing spondylitis
- 2021
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:3, s. 352-360
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate β stiffness index (indicating arterial stiffness) and, a more recently developed technique, two-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to 1) compare with age- and sex-matched controls and to 2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in AS patients.METHODS: In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.3±11.2 years, 102(68.5%) men, 146 (98%) HLA-B27 positive, were examined. Bilateral CCAs were examined for circumferential 2D strain and β stiffness index. A subgroup of 46 patients were compared with 46 age- and sex-matched controls, both groups without hypertensive disease, diabetes, myocardial infarction or stroke.RESULTS: Mean bilateral circumferential 2D strain was lower in AS patients compared with controls, 7.9±2.6% vs 10.3±1.9%, p<0.001 whereas mean bilateral β stiffness index was higher, 13.1±1.6mmHg/mm vs 12.3±1.3mmHg/mm, p=0.018. In multivariable linear regression analyses strain was associated with age, erythrocyte sedimentation rate, history of anterior uveitis and treatment with csDMARD and/or bDMARD (R2 0.33), while stiffness was associated with age (R2 0.19).CONCLUSION: Both CCA circumferential 2D strain and β stiffness index differed between AS patients and controls. Strain was associated with AS-related factors and age while stiffness with age, suggesting that the obtained results reflect different pathogenic vascular processes.
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| 8. |
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| 9. |
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| 10. |
- Ljung, Lotta, et al.
(author)
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Patterns of comorbidity and disease characteristics among patients with ankylosing spondylitis : a cross-sectional study
- 2018
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In: Clinical Rheumatology. - : Springer London. - 0770-3198 .- 1434-9949. ; 37:3, s. 647-653
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Journal article (peer-reviewed)abstract
- The knowledge of the development of comorbidities in patients with ankylosing spondylitis (AS) is limited. The aim of this study was to analyse associations between AS disease characteristics and comorbidity and to evaluate patterns of comorbidities in patients with AS. Patients with AS, fulfilling the modified New York Criteria, were identified (n =3D 346, mean age 56 +/- 15 years, 75% men, 99% HLA B27 positive). Through a review of the patient records, data on disease activity parameters, laboratory results, disease manifestations, and diagnoses of any clinically significant comorbidity was obtained. Four categories of comorbidities of interest were identified: A. arrhythmias, conduction disorders, and valvular heart disease; B. atherosclerosis and atherosclerotic CVD; C. spinal and non-spinal fractures; and D. obstructive sleep apnoea syndrome. Associations between AS disease characteristics and comorbidities in categories were assessed in logistic regression models. Differences in proportions of comorbidities was analysed using two-sided chi-square. Age was associated with all four categories of comorbidities, and male sex with arrhythmias, conduction disorders, valvular heart disease, and obstructive sleep apnoea syndrome. Early disease onset and long disease duration, respectively, were associated with arrhythmias, conduction disorders, and valvular heart disease. Obstructive sleep apnoea syndrome was associated with features of the metabolic syndrome. Patients with atherosclerotic cardiovascular disease had an increased risk of most other comorbidities, similar to, but more pronounced than patients with arrhythmias, conduction disorders and valvular heart disease. Comorbid conditions motivate clinical awareness among patients with AS. Longitudinal studies are needed to establish preventive measures.
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| 11. |
- Malmström, Erik, et al.
(author)
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Large-scale inference of protein tissue origin in gram-positive sepsis plasma using quantitative targeted proteomics.
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- The plasma proteome is highly dynamic and variable, composed of proteins derived from surrounding tissues and cells. To investigate the complex processes that control the composition of the plasma proteome, we developed a mass spectrometry-based proteomics strategy to infer the origin of proteins detected in murine plasma. The strategy relies on the construction of a comprehensive protein tissue atlas from cells and highly vascularized organs using shotgun mass spectrometry. The protein tissue atlas was transformed to a spectral library for highly reproducible quantification of tissue-specific proteins directly in plasma using SWATH-like data-independent mass spectrometry analysis. We show that the method can determine drastic changes of tissue-specific protein profiles in blood plasma from mouse animal models with sepsis. The strategy can be extended to several other species advancing our understanding of the complex processes that contribute to the plasma proteome dynamics.
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| 12. |
- Mölne, Johan, 1958, et al.
(author)
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Vascularization of normal human thyroid tissue transplanted to nude mice.
- 1987
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In: Experimental cell biology. - 0304-3568. ; 55:2, s. 104-14
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Journal article (peer-reviewed)abstract
- The vascularization of normal human thyroid tissue transplanted to nude, athymic mice was examined by light, electron microscopy and autoradiography after continuous infusion of 3H-thymidine during 2, 4 and 6 days after transplantation. Labelled vascular sprouts were found in the surrounding host connective tissue after 2 days, in between peripheral follicles after 4 days and in central parts of the transplants after 6 days. The autoradiographic observations indicate that the sprouts originated from the surrounding host tissue. The amount of sprouts increased up to a maximum after 2 weeks of transplantation. At this time large interfollicular areas were occupied by sprouts. At later observations (3-5 weeks) sprouts occurred together with typical fenestrated capillaries. After 7 weeks all sprouts had differentiated into mature vessels. Our observations suggest that the transplanted thyroid tissue induces the formation of vascular sprouts in the surrounding host connective tissue. The sprouts then penetrate and vascularize the thyroid tissue.
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| 13. |
- Smeds, Johan, et al.
(author)
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Enhanced energy conservation in houses through high performance design
- 2007
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In: Energy and Buildings. - : Elsevier BV. - 1872-6178 .- 0378-7788. ; 39:3, s. 273-278
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Journal article (peer-reviewed)abstract
- Key design features of high performance houses are investigated for improving energy efficiency in cold climates. Reference dwellings with typical constructions and system designs are compared with high performance houses using the best technology available. The dwellings used for reference are a multi-family apartment building and a single-family detached house, designed according to a mix of Nordic building codes of 2001. The high performance houses designed fulfilled the target requirements of IEA Task 28, Sustainable Solar Housing. Simulations of the buildings are performed using the computer programme DEROB-LTH and results from simulations give the hourly space-heating demand and peak load of the buildings. A comparison of reference houses to high performance solutions shows that the space-heating demand can be reduced by up to 83% for single-family houses and by up to 85% for apartment buildings. The climate data used for all simulations is Stockholm, Sweden. The environmental effects in terms of CO, equivalent emissions and use of non-renewable primary energy are quantified for each building type and construction. The energy saving potential of high performance houses in cold climates is demonstrated. (C) 2006 Elsevier B.V. All rights reserved.
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| 14. |
- Smeds, Magdalena, Teknisk licentiat, 1990-
(author)
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Exploring Tampering : Towards an Understanding of Why Improvement Efforts Sometimes Fail
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Ever-increasing competition together with increasing and changing customer demands place high demands on organisations to maintain and improve their current products and services while also developing and renewing their offerings. However, research claims that many improvement efforts carried out in organisations fail. A line of research in quality management focusing on process improvement proposes that tampering, i.e. attempts to solve problems without targeting the fundamental causes of the problem, may be one reason why some attempts to improve fail. This dissertation focuses on faulty identification of causes of problems, as well as responses to such problems made by individual employees in their day-today work.The purpose of this dissertation is to enhance knowledge on tampering as a means to understand why attempts to improve sometimes do not lead to the desired results. This dissertation also answers the research questions How is tampering manifested in various types of approaches to identifying and responding to problems? and How can customers cause employees to take tampering actions? Studying how tampering is manifested in different ways depending on how a problem is interpreted and consequently the approach taken to respond to the problem can enhance knowledge about which interpretations and actions may lead to tampering. In this dissertation, approaches are viewed as alternative courses of actions available to employees when responding to problems. Four different types of approaches are studied: inaction, workaround, local improvement and system change. In addition, possible connections between customers and tampering are discussed and in this dissertation, it is proposed that the customer may have a negative impact on employees’ improvement efforts. In addition to answering the two research questions, a contemporary understanding of the tampering concept is proposed.Three studies have been conducted: a narrative literature review, a qualitative interview study and a case study with data collection through interviews, observations and a document study. This dissertation includes five appended papers. To answer the first research question, the main findings from the papers have been analysed by applying flexible pattern matching. The flexible pattern matching process was conducted by developing a theoretical framework of approaches, summarising the findings from the papers, and then comparing the findings to the theoretical framework to identify similarities and differences. To answer the second research question, examples of tampering were studied where the customer affected which problem was to be remedied or how.The analysis in the first research question results in five manifestations of tampering in various approaches to identifying and responding to problems. Actions proposed to cause tampering are passivity/wait-and-see, symptomatic response, locally focused response, disproportionate vision and vicious spiral of firefighting. The analysis in the second research question shows multiple examples of customer-induced tampering. Customers do not tamper with an organisation’s processes, but may express demands or concerns about perceived problems or how to execute a process that the organisation complies with. The saying ‘the customer is always right’ seems to be applied especially when the demand is placed by customers who are considered particularly important for relational or economic reasons.This dissertation contributes to research on quality management in general and improvement efforts through employees approaches as well as the customers role in identifying and responding to problems in particular. This dissertation and the appended papers explore the concept of tampering, and suggest that there is a need for a revitalisation and a broader understanding of the concept in order to increase its applicability in contemporary contexts. This dissertation also explores the previously under-exploredperspective on how customers can cause organisations to take measures that – from a process perspective – create process deterioration.
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| 15. |
- Wall, Maria, et al.
(author)
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Mild Climates
- 2007
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In: Sustainable Solar Housing. Strategies and Solutions. Volume 1.. - 9781844073252 ; Volume 1, s. 237-241
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Book chapter (other academic/artistic)
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| 16. |
- Wall, Maria, et al.
(author)
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Temperate Climates
- 2007
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In: Sustainable Solar Housing. Strategies and Solutions. Volume 1.. - 9781844073252 ; Volume 1, s. 179-185
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Book chapter (other academic/artistic)
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| 17. |
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