| 1. |
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Att välja trä
- 2020. - 10
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Samlingsverk (redaktörskap) (populärvet., debatt m.m.)
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| 2. |
- Blom, Magdalena, et al.
(författare)
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The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration
- 2017
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 352:2, s. 255-264
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Tidskriftsartikel (refereegranskat)abstract
- RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration.
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| 3. |
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| 4. |
- Mold, Jeff E., et al.
(författare)
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Divergent clonal differentiation trajectories establish CD8(+) memory T cell heterogeneity during acute viral infections in humans
- 2021
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 35:8
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Tidskriftsartikel (refereegranskat)abstract
- The CD8(+) T cell response to an antigen is composed of many T cell clones with unique T cell receptors, together forming a heterogeneous repertoire of effector and memory cells. How individual T cell clones contribute to this heterogeneity throughout immune responses remains largely unknown. In this study, we longitudinally track human CD8(+) T cell clones expanding in response to yellow fever virus (YFV) vaccination at the single-cell level. We observed a drop in clonal diversity in blood from the acute to memory phase, suggesting that clonal selection shapes the circulating memory repertoire. Clones in the memory phase display biased differentiation trajectories along a gradient from stem cell to terminally differentiated effector memory fates. In secondary responses, YFV- and influenza-specific CD8(+) T cell clones are poised to recapitulate skewed differentiation trajectories. Collectively, we show that the sum of distinct clonal phenotypes results in the multifaceted human T cell response to acute viral infections.
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| 5. |
- Ahlén, Johan, et al.
(författare)
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Miljöövervakning av ängar i Västra Götalands län 2000
- 2001
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Av fältinventeringen framgår att 24 stycken objekt (50%) under de tio år som gått mellan inventeringstillfällena förändrats till det sämre. Fortsätter denna utveckling kommer det inte att dröja många decennier innan det endast finns ängar i naturreservat och på de ställen där de brukas och bevakas av ideella föreningar och särskilt intresserade brukare. Ungefär en tredjedel av de inventerade ängs- och hagmarksobjekten är sådana, vilket, extrapolerat, skulle innebära ca 90 stycken i hela länet. Om arealen antas vara jämnt fördelad skulle detta innebära en minskning från nulägets ca 320 ha till drygt 100 ha.
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| 6. |
- Bankel, Johan, et al.
(författare)
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The CDIO syllabus: a comparative study of expected student proficiency
- 2003
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Ingår i: European Journal of Engineering Education. - : Taylor & Francis. - 0304-3797 .- 1469-5898. ; 28:3, s. 297-315
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Tidskriftsartikel (refereegranskat)abstract
- Engineering students must graduate with command of a vast body of technical knowledge. They must possess personal, interpersonal and system-building skills to function in teams, and be prepared to produce products and systems. Their education must have been structured under a curriculum blending ability to combine technical expertise with ethical, innovative, philosophical and humanistic acumen. This paper describes a unique international collaboration among four universities to reform engineering education. The collaborators agreed to a statement of goals, which includes descriptions of knowledge, skills and attitudes vital to an effective education, and codifies proficiency levels expected of graduates. We developed and utilized unique stakeholder surveys both to validate our prototype and to determine desired proficiency levels. This collaboration resulted in The CDIO Syllabus, A Statement of Goals for Undergraduate Engineering Education. The syllabus is both a template and a process that can be used to customize the syllabus to others' programmes. It can define new educational initiatives/and be employed as the basis for rigorous assessment. This paper details how, with the input of industry, academia and others, we employed an engineering problem-solving paradigm to effect our redesign. It outlines the syllabus and the unique process employed to create it.
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| 7. |
- Berntsson, Lars-Olof, et al.
(författare)
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EAST-ADL 2.0 Specification
- 2008
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Rapport (refereegranskat)abstract
- This specification of the EAST ADL 2.0 is based on the EAST-ADL developed in the EAST EEA projectand has been further refined and harmonized with on-going modelling appraches in the automotiveindustry. It presents the modeling infrastructure, i.e. how the modeling elements should be represented inthe language and the UML representation. For each package a usage example is provided.The EAST-ADL 2.0 is harmonized with AUTOSAR.The metamodel and UML profile of EAST ADL 2.0 is defined in two steps: A domain (automotive)metamodel is defined, capturing only the domain specific needs of the language, without adding the UML2details. The basic concepts of UML are used for this purpose, such as classes, compositions andassociations. Based on the domain metamodel, a UML2 profile for the domain metamodel is defined,specifying stereotypes with properties and constraints.Comments on the content of this document are welcomed, and should be directed to .Please download the latest available specification and the XMI file ready for use in UML2 tools from the website.
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| 8. |
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| 9. |
- Blom, Dirk Jacobus, et al.
(författare)
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The therapeutic management of South African dyslipidaemic patients at very high cardiovascular risk (CARDIO TRACK) : a cross-sectional study
- 2020
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Ingår i: Cardiovascular Journal of Africa. - : Clinics Cardive Publishing. - 1995-1892. ; 31:5, s. 245-251
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dyslipidaemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. At the time the study was conducted, guidelines recommended a low-density lipoprotein cholesterol (LDL-C) target of less than 1.8 mmol/l and a reduction of at least 50% if the baseline LDL-C was between 1.8 and 3.5 mmol/l in patients with either very high cardiovascular risk or established atherosclerosis. In South Africa, there is a paucity of data on attainment of LDL-C goal in patients with very high cardiovascular risk who are on maximum tolerated statin with or without ezetimibe. Objective: The aim was to assess the percentage of very high cardiovascular risk South African patients with dyslipidaemia not reaching an LDL-C goal of less than 1.8 mmol/l, despite maximum tolerated statin with or without ezetimibe. Methods: This was a multi-centre, observational, cross-sectional study conducted at 15 private healthcare sector sites and one public sector site. Adults (> 18 years) with very high cardiovascular risk of familial hypercholesterolaemia receiving stable, maximum-tolerated statin therapy for at least four weeks prior to their latest lipid profile were enrolled into the study, and electronic case report forms were completed after written informed consent was provided. LDL-C goal attainment was modelled. first assuming an increase in the statin dose to the registered maximum, followed by the addition of ezetimibe or a PCSK9-inhibitor. Results: In total, 507 patients were screened. of whom 492 were eligible for study participation. One patient was excluded from the analysis because of a missing LDL-C value. Most participants were male (male 329. 67%; female 162, 33%). Most patients were either obese (223. 46.0%) or overweight (176. 36.3%). Hypertension and diabetes mellitus were frequent co-morbidities and were found in 381 (77.6%) and 316 (64.4%) patients. respectively. Eighty (16.3%) patients reported current smoking Only 68 (13.8%) patients were taking ezetimibe in addition to a statin. Reasons for not using ezetimibe included no requirement jot ezetimibe in the opinion of the treating physician (229, 48.7%). cost (149. 31.7%), physician's choice (39, 8.3%), or other (53, 11.3%), Only 161 (32.8%) of the patients attained their goal LDL-C level. In our modelling analysis. increasing the statin dose to the registered maximum and adding ezetimibe brought an additional 34.5% of patients to goal. while adding a PCSK9-inhibitor, irrespective of any other changes to lipid-lowering therapy brought over 90% of not-at-goal patients to goal. Conclusion: Most study participants were not at LDL-C goal despite maximum-tolerated statin, highlighting the need for treatment intensification in this high-risk population. Although intensifying treatment by adding a PCSK9-inhibitor brought more patients to goal, the initial addition of ezetimibe would be more reasonable, given the cost of PCSK9-inhibitors.
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| 10. |
- Blom, Hans, et al.
(författare)
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EAST-ADL : An Architecture Description Language for Automotive Software-Intensive Systems
- 2013
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Ingår i: Embedded Computing Systems. - Hershey : Information Science Reference. - 9781466639225
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Bokkapitel (refereegranskat)abstract
- EAST-ADL is an Architecture Description Language (ADL) initially defined in several European-funded research projects and subsequently refined and aligned with the more recent AUTOSAR automotive standard. It provides a comprehensive approach for defining automotive electronic systems through an information model that captures engineering information in a standardized form. Aspects covered include vehicle features, requirements, analysis functions, software and hardware components, and communication. The representation of the system’s implementation is not defined in EAST-ADL itself but by AUTOSAR. However, traceability is supported from EAST-ADL’s lower abstraction levels to the implementation level elements in AUTOSAR. In this chapter, the authors describe EAST-ADL in detail, show how it relates to AUTOSAR as well as other significant automotive standards, and present current research work on using EAST-ADL in the context of fully-electric vehicles, the functional safety standard ISO 26262, and for multi-objective optimization.
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| 11. |
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| 12. |
- Blom, Hans, et al.
(författare)
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Parallel Flow Measurements in Microstructures by Use of a Multifocal 4 x 1 Diffractive Optical Fan-Out Element
- 2002
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Ingår i: Applied Optics. - 1559-128X .- 2155-3165. ; 41:31, s. 6614-6620
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a multifocal optical fluorescence correlation spectroscopy system for parallel flow analyses. Multifocal excitation was made possible through a 4 x 1 diffractive optical fan-out element, which produces uniform intensity in all four foci. Autocorrelation flow analyses inside a 20 μm x 20 μm square microchannel, with the 4 x 1 fan-out foci perpendicular to the flow direction, made it possible to monitor different flows in all four foci simultaneously. We were able to perform cross-correlation flow analyses by turning the microstructure, thereby having all four foci parallel to the direction of flow. Transport effects of the diffusion as a function of flow and distance could then also be studied.
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| 13. |
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| 14. |
- Blom, Johan, et al.
(författare)
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Industrial Evaluation of Test Suite Generation Strategies for Model-Based Testing
- 2016
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Konferensbidrag (refereegranskat)abstract
- We report on a case study on model based testing for a commercially available telecom software system. A main purpose is to investigate how different strategies for test suite generation affect quality attributes of the generated test suites, in a realistic industrial environment. We develop a functional model in the form of an extended finite state machine, from which we generate test suites using several different (model) coverage criteria, alongside with randomly and manually generated test suites. We compare test suites with respect to fault-detection capability, incurred (source) code coverage, and test generation and execution time. The system under test is a commercially released version, not seeded with any faults, implying that exposed faults are "real" faults that passed previous testing. We did not find clear difference between coverage-based and random test suites. Test suite generation and execution is performed using the tool ERLY MARSH, developed by the first author.
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| 15. |
- Blom, Johan, 1966-
(författare)
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Model-Based Protocol Testing in an Erlang Environment
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Testing is the dominant technique for quality assurance of software systems. It typically consumes considerable resources in development projects, and is often performed in an ad hoc manner. This thesis is concerned with model-based testing, which is an approach to make testing more systematic and more automated. The general idea in model-based testing is to start from a formal model, which captures the intended behavior of the software system to be tested. On the basis of this model, test cases can be generated in a systematic way. Since the model is formal, the generation of test suites can be automated and with adequate tool support one can automatically quantify to which degree they exercise the tested software.Despite the significant improvements on model-based testing in the last 20 years, acceptance by industry has so far been limited. A number of commercially available tools exist, but still most testing in industry relies on manually constructed test cases.This thesis address this problem by presenting a methodology and associated tool support, which is intended to be used for model-based testing of communication protocol implementations in industry. A major goal was to make the developed tool suitable for industrial usage, implying that we had to consider several problems that typically are not addressed by the literature on model-based testing. The thesis presents several technical contributions to the area of model-based testing, including- a new specification language based on the functional programming language Erlang,- a novel technique for specifying coverage criteria for test suite generation, and- a technique for automatically generating test suites.Based on these developments, we have implemented a complete tool chain that generates and executes complete test suites, given a model in our specification language. The thesis also presents a substantial industrial case study, where our technical contributions and the implemented tool chain are evaluated. Findings from the case study include that test suites generated using (model) coverage criteria have at least as good fault-detection capability as equally large random test suites, and that model-based testing could discover faults in previously well-tested software where previous testing had employed a relaxed validation of requirements.
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| 17. |
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| 18. |
- Blom, Karen Ann
(författare)
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Ordinary people, meaningful pasts – Negotiating narratives in public pedagogical spaces of family history research
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation examines three family history research experiences as public pedagogical spaces, analysing the narratives presented and participants’ negotiations with these. In the context of enhanced digitalisation and rapidly developing technologies, disturbances in the form of pandemics, hackers, and wars remind us of the instability of the present, raising existential questions and reinforcing the desire to anchor oneself in the past. Despite this growing interest, academic research focusing on family history is sparse. This dissertation project is unique in its focus on a Swedish context, the selection of three specific family history experiences as case studies, and its use of a public pedagogical perspective examining relational learning beyond formal institutions intrinsically woven within the fabric of society.This dissertation uses three case studies as reflections of more extensive experiences of the phenomenon of interest in family history and the past. These include the Swedish family history television series Allt för Sverige’s previous contestants’ narratives, the results from four genetic ancestry testing companies, and participants’ narratives from two Swedish non-formal family history research courses. Analysing these further within this compilation dissertation engages a conceptual framework consisting of Rüsen’s historical narrative typology, Hall’s decoding/encoding model, and Ellsworth’s use of Public Pedagogy as relational and facilitating transitional spaces for knowledge in the making. An emphasis on the process of pedagogy, rather than the product of knowledge, is prominent in this hermeneutic phenomenological study and reflects the concept of Bildung as the cultivation of the whole person.The findings reveal a more complex picture of family historians, history, and family history research experiences than what is often portrayed. Participants deem not only the effervescent or exceptional findings and activities valuable, but the everyday banal is perceived as significant and contributes to the development of understanding and meaning. Moreover, regardless of the physical site of the experience, the infused pedagogical intent is illustrated through participants’ interactions and negotiations. In a field surrounded by rock walls their ancestor built, discovering a relative had only five spoons in a testament, or examining a deep map to trace the movements of ancestors all provide opportunities to juxtapose, confirm, and/or challenge previous knowledge with new information and experiences, reiterating the extensive reach of public pedagogy.Despite narratives presenting conflicting depictions of the past, participants of this study demonstrate agency in their negotiations, resulting in enhanced empathy and enriched historical consciousness. By exploring these family history research experiences as pedagogical spaces, this dissertation provides a more nuanced understanding of the broader field of public pedagogy and contributes new insights from Swedish and participants’ perspectives to the growing body of research on family history. It highlights the potential and benefits of examining the small, seemingly insignificant, everyday items and events. Moreover, it contributes a more comprehensive illustration of the seepage/pervasiveness of public pedagogy as complex and relational.
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| 19. |
- Blom, Kristin, et al.
(författare)
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The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis
- 2018
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : WILEY. - 0903-4641 .- 1600-0463. ; 126:1, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. Recent findings indicate that dendritic cells have a key role in the defense against the Leishmania parasite and that the activity of this cell may be modified by the eosinophil secretory protein eosinophil-derived neurotoxin (EDN). We hypothesized that the interactions between dendritic cells and EDN might be of importance in the disease development. Cellular content of EDN was analyzed by ELISA. The single-nucleotide polymorphisms at positions 405, 416, and 1122 in the EDN gene were analyzed by real-time PCR with TaqMan((R)) reagents. The study cohorts comprised 239 Sudanese subjects (65 healthy controls and 174 with VL) and 300 healthy Swedish controls. The eosinophil content of EDN was lower in VL as compared with controls (p < 0.0001). The EDN405 (G>C) genotype distribution was similar among Swedish and Sudanese controls, whereas VL subjects had a higher prevalence of the EDN405-GG genotype (p < 0.0001). The content of EDN in the eosinophils was closely linked to the EDN405 polymorphism (p = 0.0002). Our findings suggest that the predisposition to acquire VL is related to the genetic polymorphism of the EDN gene and the reduced production by the eosinophil of this gene product.
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| 20. |
- Blom, Lisa, et al.
(författare)
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Little All Children in Focus (Little ACF), evaluation of a parental support program for parents of children aged 1–2 years : study protocol for a randomized controlled trial
- 2023
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Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health and development can be promoted by strengthening and supporting parents. Research on parental support programs based on positive psychology and a health-promoting approach aimed at all parents, and in particular parents of infants is limited. All Children in Focus (ACF) is a parental support program that has been evaluated in a randomized trial in parents of children 3–12 years. The ACF is based on health promotion aiming to increase parents’ confidence and child’s well-being. In the current study, we will study the effects of a revised version of the ACF called Little ACF adapted to parents with children aged 1–2 years.Methods: The study includes a randomized controlled trial (RCT) taking place at several Child Health Centers (CHCs) in Sweden. The RCT will evaluate the efficacy of Little ACF (intervention) in comparison with four digital lectures about child development and parenting (active control). Parents are recruited at the 10-, 12-, or 18-month visits to CHC by CHC-nurses. Data to assess changes in parental competencies and child socio-emotional development are collected through online questionnaires completed by parents at five time points: baseline, post-intervention, after 6 and 12 months, and when the child is 3 years old.Discussion: The paper describes a study protocol of a randomized controlled trial evaluating the effects of a parental support program during infancy. Several issues related to the methodology and implementation are discussed.Trial registration: ClinicalTrials.gov NCT05445141. Registered on 6 July 2022.
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| 21. |
- Blom, Martin, et al.
(författare)
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Combining Contract-Based Development and Test-Driven Development
- 2009
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Konferensbidrag (refereegranskat)abstract
- Contract-based Development and Test-Driven Development are two techniques for handling and avoiding software errors. They are generally not combined and we have studied the processes associated with the techniques tosee how this combination could be done. We have found possible ways to move to and from both processes and some benefits for both ways. Moving from contracts to test cases is rather straight forward due to the completeness of the contracts, whereas moving from test cases to contracts demand some more work since the test cases are only examples of usage.
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| 22. |
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| 23. |
- Bojsen-Møller, Emil, et al.
(författare)
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Relationships between Physical Activity, Sedentary Behaviour and Cognitive Functions in Office Workers.
- 2019
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 16:23
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence from animal experiments suggests that physical activity (PA) promotes neuroplasticity and learning. For humans, most research on the relationship between PA, sedentary behaviour (SB), and cognitive function has relied on self-reported measures of behaviour. Office work is characterised by high durations of SB combined with high work demands. While previous studies have shown that fitter office workers outperform their less fit colleagues in cognitive tests, the importance of PA and SB remains unknown. This study investigated associations between objectively measured PA and SB, using hip-worn accelerometers, and cognitive functions in 334 office workers. Time spent in moderate-to-vigorous PA (MVPA) was not associated with any cognitive outcome. However, time spent in SB tended to be positively associated with words recalled in free recall (β = 0.125). For the least fit participants, the average length of MVPA bouts was favourably related to Stroop performance (β = -0.211), while for the fitter individuals, a longer average length of MVPA bouts was related to worse recognition (β = -0.216). While our findings indicate that the length of MVPA bouts was associated with better Stroop performance in the least fit participants, our findings do not support the notion that more time spent in MVPA or less time in SB is associated with better cognitive function.
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| 24. |
- Chen, DeJiu, et al.
(författare)
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DySCAS System Architecture
- 2007
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Rapport (refereegranskat)abstract
- This deliverable provides an architectural strategy and overall system design forthe DySCAS middleware system as a first step towards a complete systemspecification. The DySCAS Basic Architecture captures both the systemconceptualization and an initial function-level outline without consideringimplementation and technology details. It defines the middleware system in termsof its application and operational contexts, expected features, middleware servicesthat group functions, behaviours, as well as the structuring and implementationdecisions that are most crucial to satisfy the given set of requirements. In thisdocument, we also outline some fundamental strategies for binding themiddleware components to the target platforms and infrastructures and forhandling potential errors at both initialization-time and rum-time, while taking thetechnology support and domain needs into consideration.This deliverable also covers the rationale behind the architecture solutions andprovides a generic framework that relates architecture principles and styles, wellknownmechanisms, and reference models to the expected functionalities andqualities of DySCAS. The aim is to consolidate the proposed solutions and also tofacilitate the communications between DySCAS partners and to third-parties.
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| 25. |
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| 26. |
- Darehed, David, et al.
(författare)
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Diurnal variations in the quality of stroke care in Sweden
- 2019
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 140:2, s. 123-130
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: A recent study of acute stroke patients in England and Wales revealed several patterns of temporal variation in quality of care. We hypothesized that similar patterns would be present in Sweden and aimed to describe these patterns. Additionally, we aimed to investigate whether hospital type conferred resilience against temporal variation. Materials and Methods: We conducted this nationwide registry-based study using data from the Swedish Stroke Register (Riksstroke) including all adult patients registered with acute stroke between 2011 and 2015. Outcomes included process measures and survival. We modeled time of presentation as on/off-hours, shifts, day of week, 4-hour, and 12-hour time blocks. We studied hospital resilience by comparing outcomes across hospital types. Results: A total of 113 862 stroke events in 72 hospitals were included. The process indicators and survival all showed significant temporal variation. Door-to-needle (DTN) time within 30 minutes was less likely during nighttime than daytime (OR 0.50; 95% CI 0.41-0.60). Patients admitted during off-hours had lower odds of direct stroke unit (SU) admission (OR 0.72; 95% CI 0.70-0.75). 30-day survival was lower in nighttime vs daytime presentations (OR 0.90, 95% CI 0.84-0.96). The effects of temporal variation differed significantly between hospital types for DTN time within 30 minutes and direct SU admission where university hospitals were more resilient than specialized non-university hospitals. Conclusions: Our study shows that variation in quality of care and survival is present throughout the whole week. We also found that university hospitals were more resilient to temporal variation than specialized non-university hospitals.
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| 27. |
- Darehed, David, 1986-, et al.
(författare)
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In-hospital delays in stroke thrombolysis : every minute counts
- 2020
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Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 51:8, s. 2536-2539
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Intravenous thrombolysis is a well-established treatment for acute ischemic stroke. Our aim was to quantify the effect of each minute delay in door-to-needle time (DNT) on 90-day survival, intracerebral hemorrhagic complication <36 hours, and functional outcomes at 3 months, in routine clinical practice.Methods: Our nationwide registry-based study included 14 132 adult patient admissions with ischemic stroke receiving intravenous thrombolysis from 2010 to 2017. Outcomes were analyzed using multivariable logistic regression, adjusting for potential confounders.Results: Median DNT was 47 minutes, with an improvement from 65 to 38 minutes during the study. Median age was 74 years, and median National Institutes of Health Stroke Scale 8 points. We found a significant impact of each minute delay in DNT with reduced odds of survival by 0.6%, increased odds of intracerebral hemorrhagic and worse activities of daily living by 0.3%, and worse living conditions and mobility by 0.4%.Conclusions: Improving DNT is a key factor in achieving good outcomes after stroke. We estimate that in Sweden alone in 2017, compared with 2010, the shorter DNT achieved have saved 38 lives, avoided 8 intracerebral hemorrhagic transformations, and spared, respectively, 36, 51, and 52 patients from a worsening in activities of daily living, living conditions, and mobility. DNT is sensitive for interventions and should be targeted in quality improvement efforts.
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| 28. |
- Darehed, David, 1986-
(författare)
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The impact of organizational and temporal factors on acute stroke care in Sweden
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Acute stroke carries a high risk of morbidity and death, but early treatment can improve outcomes. Intravenous stroke thrombolysis (IVT) is one such treatment, it is however time-sensitive and show better outcomes the sooner it is given. Most studies on time to IVT so far have looked at fixed time-intervals, and studies of short delays in clinical practice are relatively scarce. Another well-established treatment is managing acute stroke patients in stroke units (SU). Admission rates to a SU as first destination of hospital care have improved over time in Sweden. In the past decade however, the rates have leveled out at around 75-80% without further improvement. A hypothesis is that in-hospital overcrowding contributes. Previous studies have shown that outcomes after stroke differ between hospital types, and also vary depending on time of admission, with higher mortality seen for off-hours, weekend and winter admissions. The reasons behind temporal variations are not fully understood, but it has been proposed that environmental, patient-related and organizational factors contribute. The overall aim of this thesis was to study the effect of organizational factors on quality of care and outcomes after stroke, primarily focusing on the role of in-hospital overcrowding, in-hospital time to IVT and time of admission, while also studying differences between hospitals.Methods: All papers in this thesis were based on data from the Swedish stroke register (Riksstroke), a national quality register that holds data on patient related factors, acute care and outcomes. Paper I included 13,955 patient admissions from 14 hospitals in Region Norrbotten and Region Skåne from 2011-2014, enriched with data on in-hospital bed occupancy. Papers II-IV included all 72 Swedish hospitals caring for patients with acute stroke. Paper II included data from 2011-2015 (N=113,862), paper III from 2011-2016 (N=132,744) and paper IV from 2010-2017 (N=14,132). Analyses included descriptive statistics, unadjusted analyses and multivariable adjusted analyses.Results: We found that each percent increase in in-hospital bed occupancy above 85% decreased admission rates to a SU as first destination of hospital care by 1.5% (odds ratio (OR) 0.985, 95% confidence interval (CI) 0.978-0.992), with significant differences between hospitals. Admission rates were also lower off-hours, compared to on-hours (OR 0.73, 95% CI 0.70-0.75). Over time, admission rates to a SU as first destination of hospital care decreased in university hospitals, while they increased in specialized non-university hospitals and community hospitals. Each minute delay in door-to-needle time (DNT) decreased the odds of 90-day survival by 0.6% (OR 0.994, 95% CI 0.992-0.996), increased the odds of ICH within 36 hours by 0.3% (OR 1.003, 95% CI 1.000-1.006), and led to significantly higher odds of a worsening in functional outcomes at 3 months by 0.3-0.4%. DNT within 30 minutes was most likely daytime, and varied between hospital types. 90-day survival was lowest for patients admitted in January (81.5%), and highest for those admitted in May (84.1%) (OR 1.28, 95% CI 1.17-1.40).Conclusion: We found that in-hospital overcrowding decrease admission rates to a SU as first destination of hospital care, and that even short delays in DNT decreases survival, increases ICH complications and leads to a worsening in functional outcomes in routine clinical practice. We also found that quality of care varied depending on time of admission and between hospitals, indicating unequal care. Organizational differences should be accessible through quality improvement efforts aiming to implement robust local guidelines for in-hospital stroke treatment.
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| 29. |
- Darehed, David, et al.
(författare)
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Time Trends and Monthly Variation in Swedish Acute Stroke Care
- 2019
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Studies of monthly variation in acute stroke care have led to conflicting results. Our objective was to study monthly variation and longitudinal trends in quality of care and patient survival following acute stroke.Methods: Our nationwide study included all adult patients (≥18 years) with acute stroke (ischemic or hemorrhagic), admitted to Swedish hospitals from 2011 to 2016, and that were registered in The Swedish Stroke Register (Riksstroke). We studied how month of admission and longitudinal trends affected acute stroke care and survival. We also studied resilience to this variation among hospitals with different levels of specialization. Results: We included 132,744 stroke admissions. The 90-day survival was highest in May and lowest in January (84.1 vs. 81.5%). Thrombolysis rates and door-to-needle time within 30 min increased from 2011 to 2016 (respectively, 7.3 vs. 12.8% and 7.7 vs. 28.7%). Admission to a stroke unit as first destination of hospital care was lowest in January and highest in June (78.3 vs. 80.5%). Stroke unit admission rates decreased in university hospitals from 2011 to 2016 (83.4 vs. 73.9%), while no such trend were observed in less specialized hospitals. All the differences above remained significant (p < 0.05) after adjustment for possible confounding factors. Conclusion: We found that month of admission and longitudinal trends both affect quality of care and survival of stroke patients in Sweden, and that the effects differ between hospital types. The observed variation suggests an opportunity to improve stroke care in Sweden. Future studies ought to focus on identifying the specific factors driving this variation, for subsequent targeting by quality improvement efforts.
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| 30. |
- Filippov, Andrei, et al.
(författare)
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Dynamics and Structure of a Bitumen Emulsion as Studied by 1H NMR Diffusometry
- 2023
-
Ingår i: ACS Omega. - : Amer Chemical Soc. - 2470-1343. ; 8:39, s. 36534-36542
-
Tidskriftsartikel (refereegranskat)abstract
- Self-diffusion in a bitumen emulsion was studied by H-1 NMR. The emulsion forms two phases: continuous and dispersed. The continuous aqueous phase contains mainly water, with the energy of activation of the diffusion process equal to that of bulk water, while its diffusivity is smaller than that of bulk water by a factor of 2. The dispersed phase consists of bitumen droplets containing confined water, whose dynamics is characterized by a fully restricted diffusion regime in cavities with sizes of similar to 0.11 mu m. Therefore, the studied bitumen emulsion can be described by a model of a complex multiple emulsion of the water/oil/water (WOW) type. The suggested model does agree well with data from H-1 NMR spectroscopy and diffusometry of the bitumen emulsion doped with paramagnetic MnSO4(aq) as well as with an additional H-1 NMR study of the emulsion structure, in which emulsion stability was compromised by freezing at 253 K.
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| 31. |
- Furst, Camilla Melin, et al.
(författare)
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Quantitative mass spectrometry to study inflammatory cartilage degradation and resulting interactions with the complement system
- 2016
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 197:8, s. 3415-3424
-
Tidskriftsartikel (refereegranskat)abstract
- Joint diseases are often characterized by inflammatory processes that result in pathological changes in joint tissues, including cartilage degradation and release of components into the synovial fluid. The complement system plays a central role in promoting the inflammation. Because several cartilage proteins are known to interact with complement, causing either activation or inhibition of the system, we aimed to investigate these interactions comprehensively. Bovine cartilage explants were cultured with IL-1α to induce cartilage degradation, followed by incubation with human serum. Label-free selected reaction monitoring mass spectrometry was used to specifically quantify complement proteins interacting with the cartilage explant. In parallel, the time-dependent degradation of cartilage was detected using mass spectrometry analysis (liquid chromatography-tandem mass spectrometry). Complement proteins resulting from activation of the classical, alternative, and terminal pathways were detected on IL-1α-stimulated cartilage at time points when clear alterations in extracellular matrix composition had occurred. Increased levels of the complement activation product C4d, as detected by ELISA in serum after incubation with IL-1α-stimulated cartilage, confirmed the selected reaction monitoring results indicating complement activation. Further, typical activated (cleaved) C3 fragments were detected by Western blotting in extracts of IL-1α-stimulated cartilage. No complement activation was triggered by cartilage cultured in the absence of IL-1α. Components released from IL-1α-stimulated cartilage during culture had an inhibitory effect on complement activation. These were released after a longer incubation period with IL-1α and may represent a feedback reaction to cartilage-triggered complement activation observed after a shorter incubation period.
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| 32. |
- Gialeli, Chrysostomi, et al.
(författare)
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Complement inhibitor CSMD1 modulates epidermal growth factor receptor oncogenic signaling and sensitizes breast cancer cells to chemotherapy
- 2021
-
Ingår i: Journal of Experimental and Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966. ; 40:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Human CUB and Sushi multiple domains 1 (CSMD1) is a large membrane-bound tumor suppressor in breast cancer. The current study aimed to elucidate the molecular mechanism underlying the effect of CSMD1 in highly invasive triple negative breast cancer (TNBC). Methods: We examined the antitumor action of CSMD1 in three TNBC cell lines overexpressing CSMD1, MDA-MB-231, BT-20 and MDA-MB-486, in vitro using scanning electron microscopy, proteome array, qRT-PCR, immunoblotting, proximity ligation assay, ELISA, co-immunoprecipitation, immunofluorescence, tumorsphere formation assays and flow cytometric analysis. The mRNA expression pattern and clinical relevance of CSMD1 were evaluated in 3520 breast cancers from a modern population-based cohort. Results: CSMD1-expressing cells had distinct morphology, with reduced deposition of extracellular matrix components. We found altered expression of several cancer-related molecules, as well as diminished expression of signaling receptors including Epidermal Growth Factor Receptor (EGFR), in CSMD1-expressing cells compared to control cells. A direct interaction of CSMD1 and EGFR was identified, with the EGF-EGFR induced signaling cascade impeded in the presence of CSMD1. Accordingly, we detected increased ubiquitination levels of EGFR upon activation in CSMD1-expressing cells, as well as increased degradation kinetics and chemosensitivity. Accordingly, CSMD1 expression rendered tumorspheres pretreated with gefitinib more sensitive to chemotherapy. In addition, higher mRNA levels of CSMD1 tend to be associated with better outcome of triple negative breast cancer patients treated with chemotherapy. Conclusions: Our results indicate that CSMD1 cross-talks with the EGFR endosomal trafficking cascade in a way that renders highly invasive breast cancer cells sensitive to chemotherapy. Our study unravels one possible underlying molecular mechanism of CSMD1 tumor suppressor function and may provide novel avenues for design of better treatment.
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| 33. |
- Gösch, Michael, et al.
(författare)
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Hydrodynamic Flow Profiling in Microchannel Structures by Single Molecule Fluorescence Correlation Spectroscopy
- 2000
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 72:14, s. 3260-3265
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we demonstrate high spatial resolution hydrodynamic flow profiling in silicon wafer based microchannels using single molecule fluorescence correlation spectroscopy (FCS). We have used confocal fluorescence microscopy to detect single tetramethylrhodamine (TMR-4-dUTP) biomolecules traversing a l fL volume element defined by an argon laser beam focus. By elevating a (10-10 M) reservoir of diluted analyte, a continuous hydrodynamic flow through the microstructure could be accomplished. The microchannel was then scanned with a diffraction-limited focus in 1-μm steps in both the vertical and the horizontal directions to determine the flow profile across a 50 × 50 μm2 channel. The flow profile measured was parabolic in both dimensions, thereby showing a Poiseuille laminar flow profile. Future microstructures can hereby be nondestructively investigated with the use of high spatial resolution confocal correlation microscopy.
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| 34. |
- Hall, Håkan, et al.
(författare)
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In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and 67/68Ga-labeled haptens by pretargeting
- 2012
-
Ingår i: American Journal of Nuclear Medicine and Molecular Imaging. - 2160-8407. ; 2:2, s. 141-150
-
Tidskriftsartikel (refereegranskat)abstract
- The carcinoembryonic antigen (CEA) was visualized in vitro in tissue from patients with colorectal cancer with trivalent bispecific antibody TF2 and two hapten molecules, [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga-IMP485 by means of pretargeting. Colorectal cancer tissue samples obtained from surgery at Uppsala University Hospital, were frozen fresh and cryosectioned. The two hapten molecules comprising 1,4,7-triazacyclononanetriacetic acid chelate moiety (NOTA) were labeled with (67)Ga or (68)Ga. The autoradiography was conducted by incubating the tissue samples with the bispecific antibody TF2, followed by washing and incubation with one of the radiolabeled hapten molecules. After washing, drying and exposure to phosphor imager plates, the autoradiograms were analyzed and compared to standard histochemistry (hematoxylin-eosin). Pronounced binding was found in the tissue from colorectal cancer using the bispecific antibody TF2 and either of the haptens [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga-IMP485. Distinct binding was also detected in the epithelium of most samples of neighboring tissue, taken at a minimum of 10 cm from the site of the tumor. It is concluded that pretargeting CEA with the bispecific antibody TF2 followed by the addition of (67/68)Ga-labeled hapten is extremely sensitive for visualizing this marker for colorectal cancer. This methodology is therefore a very specific complement to other histochemical techniques in the diagnosis of biopsies or in samples taken from surgery. Use of the pretargeting technique in vivo may also be an advance in diagnosing patients with colorectal cancer, either using (67)Ga and SPECT or (68)Ga and PET.
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| 35. |
- Happonen, Kaisa, et al.
(författare)
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COMP-C3b Complexes in Rheumatoid Arthritis with Severe Extraarticular Manifestations
- 2013
-
Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 40:12, s. 2001-2005
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate biomarker patterns in rheumatoid arthritis (RA) with extraarticular manifestations. Methods. Cartilage oligomeric matrix protein (COMP), COMP-C3b, and soluble terminal complement complexes (sTCC) were measured by ELISA. Results. COMP-C3b levels were higher in patients with RA than in healthy controls and lower in extraarticular RA (ExRA) than in RA controls. In patients with ExRA, sTCC levels were higher than in RA controls, and correlated inversely with serum COMP-C3b levels in the ExRA group. Conclusion. Patients with ExRA had lower levels of COMP-C3b. This may be a consequence of complement consumption or a lower potential for COMP from these patients to activate complement.
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| 36. |
- Hart Reeve, Andrew, et al.
(författare)
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The formation of the Indo-Pacific montane avifauna
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The processes generating the earth’s montane biodiversity remain a matter of debate. Two contrasting hypotheses have been advanced to explain how montane populations form: via direct colonization from other mountains, or, alternatively, via upslope range shifts from adjacent lowland areas. We seek to reconcile these apparently conflicting hypotheses by asking whether a species’ ancestral geographic origin determines its mode of mountain colonization. Island-dwelling passerine birds at the faunal crossroads between Eurasia and Australo-Papua provide an ideal study system. We recover the phylogenetic relationships of the region’s montane species and reconstruct their ancestral geographic ranges, elevational ranges, and migratory behavior. We also perform genomic population studies of three super-dispersive montane species/clades with broad island distributions. Eurasian-origin species populated archipelagos via direct colonization between mountains. This mode of colonization appears related to ancestral adaptations to cold and seasonal climates, specifically short-distance migration. Australo-Papuan-origin mountain populations, by contrast, evolved from lowland ancestors, and highland distribution mostly precludes their further colonization of island mountains. Our study explains much of the distributional variation within a complex biological system, and provides a synthesis of two seemingly discordant hypotheses for montane community formation.
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| 37. |
- Hensing, Gunnel, 1956, et al.
(författare)
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Differences in how women and men in a Swedish population-based sample think about sick leave: A cross-sectional vignette study
- 2024
-
Ingår i: WORK-A JOURNAL OF PREVENTION ASSESSMENT & REHABILITATION. - 1051-9815 .- 1875-9270. ; 77:3, s. 827-838
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gender differences in attitudes towards depression gives reason to believe that sociocultural gender norms play a role in other areas. OBJECTIVE: The aim was to test (i) if the likelihood to think that sick leave with depression symptoms is not reasonable varies between women and men, and (ii) if the likelihood to think sick leave is not reasonable varies depending on the gender of the individual with depression symptoms. METHODS: A study population of 3147 participants responded to a web-survey with a written case briefly describing a man or woman with symptoms of depression. Respondents were asked if they thought it is reasonable that the person was sick listed for two weeks. Logistic regression was used to analyse the data. RESULTS: After controlling for age, education, self-rated health, and respondent's own experience of sickness absence the adjusted OR was 1.45 (95% CI 1.25-1.67) for men being less likely to think sick-leave was reasonable. Gender difference decreased when adjusting for negative attitudes towards depression (adjusted OR 1.24, 95% CI 1.06-1.44). No difference was found between how women and men thought about sick leave in relation to the gender of the case described in the vignette. CONCLUSION: Men were more likely to think that sick leave was not reasonable with decreased OR after adjustment for negative attitudes towards depression. Gender norms might be part of the explanation for differences but are challenging to test. This study contributes to a bourgeoning research field on gendered attitudes and sick leave, in terms of theoretical reasoning and methodological choice.
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| 38. |
- Hernández, Aura Rocio, et al.
(författare)
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New concepts for transdermal delivery of oxygen based on catalase biochemical reactions studied by oxygen electrode amperometry
- 2019
-
Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 306, s. 121-129
-
Tidskriftsartikel (refereegranskat)abstract
- The development of formulation concepts for improved skin tissue oxygenation, including methods for measuring oxygen (O) transport across biological barriers, are important research topics with respect to all processes that are affected by the O concentration, such as radiation therapy in oncology treatments, wound healing, and the general health status of skin. In this work we approach this topic by a novel strategy based on the antioxidative enzyme catalase, which is naturally present in the skin organ where it enables conversion of the reactive oxygen species hydrogen peroxide (HO) into O. We introduce various applications of the skin covered oxygen electrode (SCOE) as an in-vitro tool for studies of catalase activity and function. The SCOE is constructed by placing an excised skin membrane directly on an O electrode and the methodology is based on measurements of the electrical current generated by reduction of O as a function of time (i.e. chronoamperometry). The results confirm that a high amount of native catalase is present in the skin organ, even in the outermost stratum corneum (SC) barrier, and we conclude that excised pig skin (irrespective of freeze-thaw treatment) represents a valid model for ex vivo human skin for studying catalase function by the SCOE setup. The activity of native catalase in skin is sufficient to generate considerable amounts of O by conversion from HO and proof-of-concept is presented for catalase-based transdermal O delivery from topical formulations containing HO. In addition, we show that this concept can be further improved by topical application of external catalase on the skin surface, which enables transdermal O delivery from 50 times lower concentrations of HO. These important results are promising for development of novel topical or transdermal formulations containing low and safe concentrations of HO for skin tissue oxygenation. Further, our results indicate that the O production by catalase, derived from topically applied S. epidermidis (a simple model for skin microbiota) is relatively low as compared to the O produced by the catalase naturally present in skin. Still, the catalase activity derived from S. epidermidis is measurable. Taken together, this work illustrates the benefits and versatility of the SCOE as an in vitro skin research tool and introduces new and promising strategies for transdermal oxygen delivery, with simultaneous detoxification of HO, based on native or topically applied catalase.
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| 39. |
- Hopfner, M., et al.
(författare)
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Validation of MIPAS ClONO2 measurements
- 2007
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 7, s. 257-281
-
Tidskriftsartikel (refereegranskat)abstract
- Altitude profiles of ClONO2 retrieved with the IMK (Institut fur Meteorologie und Klimaforschung) science-oriented data processor from MIPAS/Envisat (Michelson Interferometer for Passive Atmospheric Sounding on Envisat) mid-infrared limb emission measurements between July 2002 and March 2004 have been validated by comparison with balloon-borne (Mark IV, FIRS2, MIPAS-B), airborne (MIPAS-STR), ground-based (Spitsbergen, Thule, Kiruna, Harestua, Jungfraujoch, Izana, Wollongong, Lauder), and spaceborne (ACE-FTS) observations. With few exceptions we found very good agreement between these instruments and MIPAS with no evidence for any bias in most cases and altitude regions. For balloon-borne measurements typical absolute mean differences are below 0.05 ppbv over the whole altitude range from 10 to 39 km. In case of ACE-FTS observations mean differences are below 0.03 ppbv for observations below 26 km. Above this altitude the comparison with ACE-FTS is affected by the photochemically induced diurnal variation of ClONO2. Correction for this by use of a chemical transport model led to an overcompensation of the photochemical effect by up to 0.1 ppbv at altitudes of 30-35 km in case of MIPAS-ACE-FTS comparisons while for the balloon-borne observations no such inconsistency has been detected. The comparison of MIPAS derived total column amounts with ground-based observations revealed no significant bias in the MIPAS data. Mean differences between MIPAS and FTIR column abundances are 0.11 +/- 0.12 x 10(14) cm(-2) (1.0 +/- 1.1%) and -0.09 +/- 0.19 x 10(14) cm(-2) (-0.8 +/- 1.7%), depending on the coincidence criterion applied. chi(2) tests have been performed to assess the combined precision estimates of MIPAS and the related instruments. When no exact coincidences were available as in case of MIPAS-FTIR or MIPAS-ACE-FTS comparisons it has been necessary to take into consideration a coincidence error term to account for chi(2) deviations. From the resulting chi(2) profiles there is no evidence for a systematic over/underestimation of the MIPAS random error analysis.
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| 40. |
- Johansson, Marie, et al.
(författare)
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Expert competence for sustainable timber engineering : a master program in close cooperation between industry and academia
- 2014
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Ingår i: WCTE 2014 - World Conference on Timber Engineering, Proceedings.
-
Konferensbidrag (refereegranskat)abstract
- From a legislative point of view it has been possible to build timber buildings with arbitrary number of storeys in Sweden during almost two decades. Several buildings up to eight storeys have been completed during that time, but the competence for planning and building such structures are limited to a handful of actors. This fact has been recognized by funders of research/education and an educational program for spreading the knowledge within the industry led by Linnaeus University is financed since about two years. Particularly interesting in the programme is that the courses are developed in cooperation between the industry and the academia. The courses are to fulfil needs with respect to knowledge, but also with respect to format so that the main target group, skilled engineers within the industry, can find the motivation to follow a course or lager parts of the program.
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| 41. |
- Koro, Catalin, et al.
(författare)
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Carbamylation of immunoglobulin abrogates activation of the classical complement pathway
- 2014
-
Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 44:11, s. 3403-3412
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Tidskriftsartikel (refereegranskat)abstract
- Post-translational modifications of proteins significantly affect their structure and function. The carbamylation of positively charged lysine residues to form neutral homoitrulline occurs primarily under inflammatory conditions through myeloperoxidase-dependent cyanate (CNO-) formation. We analyzed the pattern of human IgG(1) carbamylation under inflammatory conditions and the effects that this modification has on the ability of antibodies to trigger complement activation via the classical pathway. We found that the lysine residues of IgG(1) are rapidly modified after brief exposure to CNO-. Interestingly, modifications were not random, but instead limited to only few lysines within the hinge area and the N-terminal fragment of the CH2 domain. A complement activation assay combined with mass spectrometry analysis revealed a highly significant inverse correlation between carbamylation of several key lysine residues within the hinge region and N-terminus of the CH2 domain and the proper binding of C1q to human IgG(1) followed by subsequent complement activation. This severely hindered complement-dependent cytotoxicity of therapeutic IgG(1). The reaction can apparently occur in vivo, as we found carbamylated antibodies in synovial fluid from rheumatoid arthritis patients. Taken together, our data suggest that carbamylation has a profound impact on the complement-activating ability of IgG(1) and reveals a pivotal role for previously uncharacterized lysine residues in this process.
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| 42. |
- Linders, Johan, et al.
(författare)
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Complement Component 3 Is Required for Tissue Damage, Neutrophil Infiltration, and Ensuring NET Formation in Acute Pancreatitis
- 2020
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Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 61:6, s. 163-176
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neutrophil extracellular traps (NETs) are known to play an important role in the pathophysiology of acute pancreatitis (AP). Activation of the complement cascade has been shown to occur in AP. The aim of this study was to examine whether complement component 3 is involved in the generation of NETs in AP.METHODS: AP was induced in wild-type and C3-deficient mice by retrograde infusion of taurocholate into the pancreatic duct. Blood, lung, and pancreas tissue were collected and MPO activity was determined in lung and pancreas tissue. Histological examination of the inflamed pancreas was performed. Plasma levels of CXCL2, MMP-9, IL-6, and DNA-histone complexes as well as pancreatic levels of CXCL1 and CXCL2 were determined by use of enzyme-linked immunosorbent assay. NETs were detected in the pancreas by electron microscopy. The amount of MPO and citrullinated histone 3 in neutrophils isolated from bone marrow was examined using flow cytometry.RESULTS: In C3-deficient mice, challenge with taurocholate yielded much fewer NETs in the pancreatic tissue compared with wild-type controls. Taurocholate-induced blood levels of amylase, tissue injury, and neutrophil recruitment in the pancreas were markedly reduced in the mice lacking C3. Furthermore, MPO levels in the lung, and plasma levels of IL-6, MMP-9, and CXCL2 were significantly lower in the C3-deficient mice compared to wild-type mice after the induction of AP. In vitro studies revealed that neutrophils from C3-deficient mice had normal NET-forming ability and recombinant C3a was not capable of directly inducing NETs formation in the wild-type neutrophils.CONCLUSION: C3 plays an important role in the pathophysiology of AP as it is necessary for the recruitment of neutrophils into the pancreas and ensuring NETs formation. Targeting C3 could hence be a potential strategy to ameliorate local damage as well as remote organ dysfunction in AP.
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| 43. |
- Lindström, Johan, et al.
(författare)
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Using PCA and Global Smoothing to Explore Differences between Global Vegetation Models
- 2011
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Ingår i: Proceedings of the 58th World Statistics Congress of the International Statistical Institute (ISI 2011). - 9789073592339 ; , s. 3946-3952
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A common method for comparing the result of different global circulation models (GCMs) under different emission scenarios is to study global climate response variables, such as mean temperature. An interesting alternative measure of climate sensitivity is to study the biosphere’s response to the different climate scenarios. The Lund-Postdam-Jena (LPJ) global vegetation model and its extension LPJ-GUESS is a dynamic global vegetation model that can be coupled to GCMs and used to explore the effect of varying climates on vegetation and carbon uptake. Using the output from different GCMs under different emission scenarios LPJ-GUESS can be used to generate global vegetation and carbon uptake patterns that are specific to each forcing climate scenario. We investigate if important regional and global differences exist between the vegetation patterns from different GCMs and emission scenarios. An important question is if potential differences are primarily due to the different emission scenarios or to the different GCMs. In order for us to carry out the above analysis we need to both reduce the noise in the LPJ-GUESS predictions and reduce the vast amount of data. To accomplish both these goals we compute smooth principal components. A problem when computing the PCA and the smoothing is that LPJ-GUESS output is generated on a regular longitude-latitude grid, implying that both the size and distance between grid cells vary. To handle this irregular data on a sphere we use a Gaussian Markov random field (GMRF) approximation of Thin Plate Splines (TPS) that generalises the TPS to general manifolds (such as a sphere). The well known computational advantages of GMRFs greatly aids the analysis, given the large amount of data obtained from LPJ-GUESS.
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| 44. |
- Lu, Xiaohu, et al.
(författare)
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Structural and chemical imaging analysis of bitumen
- 2021
-
Ingår i: International Journal on Road Materials and Pavement Design. - : Taylor and Francis Ltd.. - 1468-0629 .- 2164-7402. ; 22:4, s. 852-870
-
Tidskriftsartikel (refereegranskat)abstract
- Microstructures of bitumen surfaces (both air-cooled and fractured) were imaged by atomic force microscopy (AFM) and chemically characterised by time-of-flight secondary ion mass spectrometry (TOF-SIMS). For certain air-cooled bitumen surfaces, bee structures were observed by AFM, and chemical explanation by wax crystallisation was confirmed by TOF-SIMS analysis. Unlike the air-cooled surfaces, the fracture surfaces generally did not show clear structure patterns. Furthermore, TOF-SIMS analysis was conducted on the tube-like or worm structures which were generated by environmental scanning electron microscopy (ESEM) on the bitumen surfaces. In general, very small chemical differences were observed between the structured and unstructured areas, as well as between different areas of the structure. To understand the formation of the ESEM structures, possible contributing factors were examined, from which a mechanism involving electron-induced heating was proposed.
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| 45. |
- Lu, Xiaohu, et al.
(författare)
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Visualization and chemical analysis of bitumen microstructures
- 2019
-
Ingår i: RILEM Bookseries. - Cham : Springer International Publishing. ; , s. 168-173
-
Konferensbidrag (refereegranskat)abstract
- Microstructures of bitumen were investigated using atomic force microscopy (AFM) and environmental scanning electron microscopy (ESEM), and a chemical characterization was successfully carried out using time-of-flight secondary ion mass spectrometry (TOF-SIMS). The bee structures were observed by AFM, for which a chemical explanation by wax was confirmed by the TOF-SIMS analysis. A tube pattern or worm structures were generated and visualized by ESEM on bitumen surfaces. Chemical differences between the structured and unstructured areas, as well as between different areas of the structure, were observed. A mechanism for the structure formation on bitumen surface during ESEM analysis is suggested.
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| 46. |
- Mold, Jeff E., et al.
(författare)
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Clonally heritable gene expression imparts a layer of diversity within cell types
- 2024
-
Ingår i: Cell systems. - : Elsevier BV. - 2405-4720. ; 15:2, s. 149-
-
Tidskriftsartikel (refereegranskat)abstract
- Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high-coverage single-cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene expression patterns among different clones of cells of the same type in vivo. We combined chromatin accessibility and RNA profiling on different lymphocyte clones to reveal thousands of regulatory regions exhibiting interclonal variation, which could be directly linked to interclonal variation in gene expression. Our findings identify a source of cellular diversity, which may have important implications for how cellular populations are shaped by selective processes in development, aging, and disease. A record of this paper's transparent peer review process is included in the supplemental information.
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| 47. |
- Nilsson, Josefin A., 1985-, et al.
(författare)
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Effects of Fertilization on Wood Formation in Naturally Regenerated Juvenile Silver Birch in a Norway Spruce Stand in South Sweden
- 2021
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Ingår i: Forests. - Basel : MDPI. - 1999-4907. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigates wood density and anatomy of juvenile silver birch stems in Sweden,grown in mixed conifer stands. Our aim is to investigate if fertilization provides increased growth, aswell as an eventual reduction in stem wood density. Measurements of basic density, ring width, cellwall thickness, and vessels are analyzed for 20 birch trees. Bark to pith radial sections are analyzedusing a light microscope and the freeware ImageJ to compare treatments and ages. The results showthat trees with fertilizer treatment have wider growth rings and thinner cell wall thickness comparedto unfertilized trees. The fertilized trees also have a lower cambium age at the same height and thesame diameter, and a slightly lower stem mean density (420 kg m3) than the unfertilized stems(460 kg m3). Fertilizer is a significant determinant of density and cell wall thickness in nonlinearmodels. The fertilized trees have increased growth and reached a fixed diameter earlier. The agedifference between the trees likely explains some of the differences in cell wall thickness. This studysupports the use of fertilizer as a silvicultural option for increasing the growth rate of silver birch fora relatively small reduction of wood density.
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| 48. |
- Nilsson, Mats
(författare)
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Post-Secular Tourism : A Study of Pilgrimages to Santiago de Compostela
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis takes its starting-point in the post-secular changes in society and how these interplay with tourism. In spite of the intensive academic debate on and theorisation of the post-secular and post-secularism, the role of tourism in this change, called the return of religion, has not been studied. Conversely, neither has the role of post-secularism in tourism been addressed. The overall aim of this thesis is to describe and understand the relation between post-secularism and tourism. Specifically, the aim is to clarify and understand the relation between religious faith, place and tourism in our time on the basis of a case study of pilgrimage in the area of Santiago de Compostela. In other words, the thesis highlights the role of tourism in the emergence of what is now called the post-secular condition.Santiago de Compostela is a Catholic Church instituted holy city, which has increase in number of visitors. The growing number of pilgrimages and their significance lend vitality to the return of religion phenomenon. The empirical material derives primarily from individual interviews as narratives are considered to be a vital dimension to constitute and construct human realities and modes of being.This thesis shows that contemporary pilgrimage to Santiago de Compostela is a post-secular performative and place-creating phenomenon. Post-secular tourist places are subjective and spiritually meaningful destinations. Unlike traditional pilgrimage destinations a key attribute is that neither traditional religious faith nor loyalty to institutionalised faith are (pre)ordained. Rather, place is constructed by the narratives and experiences of post-secular tourists.
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| 49. |
- Nordblom, Jonathan, et al.
(författare)
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FGF1 containing biodegradable device with peripheral nerve grafts induces corticospinal tract regeneration and motor evoked potentials after spinal cord resection
- 2012
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 30:2, s. 91-102
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Repairing the spinal cord with peripheral nerve grafts (PNG) and adjuvant acidic fibroblast growth factor (FGF1) has previously resulted in partial functional recovery. To aid microsurgical placement of PNGs, a graft holder device was previously developed by our group. In hope for a translational development we now investigate a new biodegradable graft holder device containing PNGs with or without FGF1.Methods: Rats were subjected to a T11 spinal cord resection with subsequent repair using twelve white-to-grey matter oriented PNGs prepositioned in a biodegradable device with or without slow release of FGF1. Animals were evaluated with BBB-score, electrophysiology and immunohistochemistry including anterograde BDA tracing.Results: Motor evoked potentials (MEP) in the lower limb reappeared at 20 weeks after grafting. MEP responses were further improved in the group treated with adjuvant FGF1. Reappearance of MEPs was paralleled by NF-positive fibers and anterogradely traced corticospinal fibers distal to the injury. BBB-scores improved in repaired animals.Conclusions: The results continue to support that the combination of PNGs and FGF1 may be a regeneration strategy to reinnervate the caudal spinal cord. The new device induced robust MEPs augmented by FGF1, and may be considered for translational research.
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| 50. |
- Pais, Jorge C., et al.
(författare)
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Crumb Rubber Modified Binders
- 2023
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Ingår i: RILEM State-of-the-Art Reports. - : Springer Nature. ; , s. 37-67
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- RILEM Technical Committee 279 WMR is dedicated to the Valorization of Waste and Secondary Materials for Roads. Its Task Group 2 investigated Crumb Rubber (CR) as an additive to enhance the performance of bitumen. CR recycled from end-of-life tires (ELTs) was chosen for this investigation because crumb rubber modified bitumen (CRMB) has been used to improve bituminous mixtures performance for fatigue and reflective cracking. The success of these mixtures is due to the CRMB viscosity that allows the use of an increased amount of bitumen compared to conventional mixtures. Because the viscosity of the CRMB is a function of the CR surface, and presently various types of CRs are produced, it is crucial to verify how these materials perform as a bitumen modifier. Interlaboratory experiments were performed on four types of CR, obtained from mechanical grinding, cryogenic process, waterjet pulverization and reacted and activated rubber. Three base, 35/50, 50/70 and 70/100, bitumen were used for the modification. Mechanical and chemical properties of CRMB were investigated. Despite some differences in the non-mechanical tests, i.e., penetration, softening point and viscosity, the results of the mechanical tests (complex shear modulus) suggest that the bitumen penetration grade ultimately dictates CRMB response.
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