| 1. |
- Carlsson, Vanja, 1985, et al.
(författare)
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Intervjuer
- 2020
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Ingår i: Andra hjälpen: allt du behöver veta för att skriva en uppsats. Abrahamson Löfström, C., och Rombach, B. (red.). - Lund : Studentlitteratur. - 9789144130682 ; , s. 93-105
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Bokkapitel (refereegranskat)
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| 2. |
- Magnusson, Björn, 1976, et al.
(författare)
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Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism.
- 2008
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Ingår i: Metabolism: clinical and experimental. - : Elsevier BV. - 1532-8600. ; 57:9, s. 1307-13
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Tidskriftsartikel (refereegranskat)abstract
- Members of the cell death-inducing DFF45-like effector (CIDE) gene family have been shown to regulate lipid metabolism. In this article, we report that the third member of the human CIDE family, CIDEC, is down-regulated in response to a reduced caloric intake. The down-regulation was demonstrated by microarray and real-time polymerase chain reaction analysis of subcutaneous adipose tissue in 2 independent studies on obese patients undergoing treatment with a very low calorie diet. By analysis of CIDEC expression in 65 human tissues, we conclude that human CIDEC is predominantly expressed in subcutaneous adipocytes. Together, these observations led us to investigate the effect of decreased CIDEC expression in cultured 3T3-L1 adipocytes. Small interfering RNA-mediated knockdown of CIDEC resulted in an increased basal release of nonesterified fatty acids, decreased responsiveness to adrenergic stimulation of lipolysis, and increased oxidation of endogenous fatty acids. Thus, we suggest that CIDEC is a regulator of adipocyte lipid metabolism and may be important for the adipocyte to adapt to changes in energy availability.
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| 3. |
- Rohrer, Julia M., et al.
(författare)
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Putting the Self in Self-Correction : Findings From the Loss-of-Confidence Project
- 2021
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Ingår i: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 16:6, s. 1255-1269
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Tidskriftsartikel (refereegranskat)abstract
- Science is often perceived to be a self-correcting enterprise. In principle, the assessment of scientific claims is supposed to proceed in a cumulative fashion, with the reigning theories of the day progressively approximating truth more accurately over time. In practice, however, cumulative self-correction tends to proceed less efficiently than one might naively suppose. Far from evaluating new evidence dispassionately and infallibly, individual scientists often cling stubbornly to prior findings. Here we explore the dynamics of scientific self-correction at an individual rather than collective level. In 13 written statements, researchers from diverse branches of psychology share why and how they have lost confidence in one of their own published findings. We qualitatively characterize these disclosures and explore their implications. A cross-disciplinary survey suggests that such loss-of-confidence sentiments are surprisingly common among members of the broader scientific population yet rarely become part of the public record. We argue that removing barriers to self-correction at the individual level is imperative if the scientific community as a whole is to achieve the ideal of efficient self-correction.
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| 4. |
- Bertmar, Sofia, et al.
(författare)
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Who's Most Targeted and Does My New Adblocker Really Help : A Profile-based Evaluation of Personalized Advertising
- 2021
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Ingår i: Proc. ACM CCS Workshop on Privacy in the Electronic Society (ACM WPES @CCS). - New York, NY, USA : ACM Digital Library. - 9781450385275
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Konferensbidrag (refereegranskat)abstract
- There is limited prior work studying how the ad personalization experienced by different users is impacted by the use of adblockers, geographic location, the user's persona, or what browser they use. To address this void, this paper presents a novel profile-based evaluation of the personalization experienced by carefully crafted user profiles. Our evaluation framework impersonates different users and captures how the personalization changes over time, how it changes when adding or removing an extension, and perhaps most importantly how the results differ depending on the profile's persona (e.g., interest, occupation, age, gender), geographic location (US East, US West, UK), what browser extension they use (none, AdBlock, AdBlock Plus, Ghostery, CatBlock), what browser they use (Chrome, Firefox), and whether they are logged in to their Google account. By comparing and contrasting observed differences we provide insights that help explain why some user groups may feel more targeted than others and why some people may feel even more targeted after having turned on their adblocker.
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| 5. |
- Carlsson, Julia, et al.
(författare)
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Att planera för hela skogslandskapet : utmaningar och möjligheter
- 2016
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Rapport (populärvet., debatt m.m.)abstract
- Skogens många värden behöver samplaneras och sättas i sitt sammanhang utifrån ett landskapsperspektiv. Vi intervjuade skogsägare och skogliga intressenter om hur de ser på skogens värden, äganderätten och skogspolitiska förutsättningar, samt synen på att samarbeta och ta hänsyn till varandras intressen. Vi utgår från behov identifierade i planeringsprocesser som inkluderar många deltagare och intressen, när det gäller att förbättrakommunikation, information och mötesplatser. Vi ser tre möjliga verktyg för att skapa förutsättningar för ett landskapsperspektiv i planeringen av skogens värden: en landskapslots, en samverkansarena, samt utformningen och användandet av skogsbruksplanen.
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| 6. |
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| 7. |
- Carlsson, Julia, et al.
(författare)
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Combining scientific and stakeholder knowledge in future scenario development - A forest landscape case study in northern Sweden
- 2015
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Ingår i: Forest Policy and Economics. - : Elsevier BV. - 1389-9341 .- 1872-7050. ; 61, s. 122-134
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Tidskriftsartikel (refereegranskat)abstract
- Northern Swedish forests provide multiple ecosystem services. Integrating these values into the forest planning process frequently requires that not only forest owners but also other stakeholders be involved. The objective of this study is to assess the potential of future scenario development as a tool in forest planning. In a case study of the Vilhelmina municipality in northern Sweden, forest owners and stakeholders were interviewed, and aworkshopwas held to discuss important factors for the future development of the local landscape regarding ecological, socioeconomic and political issues. Combined with a researcher-conducted process, this resulted in three alternative scenarios. We conclude that the scenario development process has produced information that can be used in forest planning. The participatory element of the scenario development process could be extended further to enhance communication, learning and knowledge exchange. The participants' contribution to the scenario construction could also be elaborated, e.g., by further involving stakeholders in the formulation of alternative future manifestations and in the elaboration of scenarios. To achieve this, it is necessary to adapt the quantitative methods to the participatory situation, to foster discussion qualities, to secure representation and increase motivation for participation in different ways.
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| 8. |
- Carlsson, Josefine, et al.
(författare)
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Health risks from exposure to chemicals in clothing - non-regulated halogenated aromatic compounds
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The objective of the present study was to investigate some commonly detected halogenated textile pollutants for their hazardous properties and bioavailability. Release into artificial sweat and skin absorption in vitro were examined as well as mutagenic effects by Ames test, and skin-sensitizing properties from a peptide reactivity assay combined with a cell test.All investigated compounds were shown to migrate from the textile into sweat and be absorbed by skin, although to a different extent. The experimental values for migration were found to be up to 390 times higher compared to literature values. Two of the studied compounds, 2,5-dinitrochlorobenzene and 3,5-dinitrobromobenzene, both exhibited mutagenic effects in the Ames test, while both 2,5-dinitrochlorobenzene and 2,6-dichlorobenzene-1,4-diamine showed strong skin sensitization potencies, thus being classified as substances of UN GHS subcategory 1A.Risks for the induction of skin allergy and other non-carcinogenic effects from dermal exposure to the individual compounds were found low, even when considering clothing with the highest reported levels. However, the complex mixtures of chemicals often present in garments may still constitute a health risk, especially when considering the many hours of daily exposure. The toxicity of other frequently occurring chemicals as well as the chemical “cocktail” in textiles should be further investigated.
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| 9. |
- Carlsson, Julia
(författare)
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Intraprenad som driftsform för gymnasieskolan : Utvärdering av intraprenad på Angeredsgymnasiet 2016-1019
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I denna rapport presenteras resultatet av en utvärdering som är gjord av intraprenad på Angeredsgymnasiet i Göteborgs stad mellan åren 2016-2019. Utbildningsförvaltningen gav uppdraget att utvärdera intraprenad på Angeredsgymnasiet till Förvaltningshögskolan vid Göteborgs universitet, och sedan hösten 2016 har ett arbete pågått med att följa introduktion och användning av driftsformen. Utvärderingsuppdraget flyttade hösten 2019 från Förvaltningshögskolan till Sektionen för vård, arbetsliv och välfärd vid Borås Högskola, var arbetet avslutades. Studien är genomförd av Julia Carlsson, doktor i offentlig förvaltning, som idag är verksam som lärare och forskare vid Högskolan i Borås.
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| 10. |
- Carlsson, Julia, et al.
(författare)
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Lean i äldreomsorg – en cylinderformad kloss i ett fyrkantigt hål? : En fallstudie om huruvida lean är en passande modell för svensk kommunal äldreomsorg
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Managementmodellen lean uppstod i bilindustrin men har applicerats på helt andra typer av branscher, varav offentlig sektor är en av dem. Tidigare forskning visar att lean applicerat på offentliga tjänster passar bättre när tjänsten är av mer homogen karaktär såsom sophantering och parkförvaltning. Ändå visar en kartläggning av lean i Sverige att flest kommuner har implementerat lean inom äldreomsorg - vilket är en heterogen tjänst med höga krav på individanpassning.Syftet med den här fallstudien är att undersöka om lean således är en passande managementmodell för kommunal äldreomsorg. Baserat på sju intervjuer i två svenska kommuner har studien utgått från vad som påverkar kommuners möjlighet att arbeta lean på en filosofisk nivå (lean thinking).Resultatet visar att lean thinking i sin helhet inte är passande för äldreomsorgen, vilket framför allt beror på att offentliga verksamheter utöver brukaren ser socialnämnden och skattebetalare som kunder, vilket försvårar arbetet med lean som utgår från värde enligt kundens perspektiv. Däremot visar verksamheterna att de genom att arbeta med lean framförallt förbättrar processer som inte involverar brukaren, exempelvis administration och förrådsoch tvätthantering. Det frigör tid till värdeskapande aktiviteter för brukaren. Vi finner också att myndigheten som reglerar svensk äldreomsorg möjliggör för lean-inspirerat arbete inom äldreomsorg, framför allt på grund av arbetet med att utgå och anpassa tjänster till de faktiska behoven för brukaren istället för att begränsas till det redan befintliga tjänsteutbudet.
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| 11. |
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| 12. |
- Carlsson, Julia, 1980
(författare)
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När idéer får liv - Om intraprenader i tre kommuner : Sustainable ideas - the idea of "contracting in" in three Swedish municipalities
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the early 2000s an idea regarding how to organise the Swedish public sector, called internal contracts, attracted attention from many different public authorities in Sweden. Organising in the form of internal contracts means that units within a public authority are given more autonomy to run their own affairs. A distinct feature of the internal contracts model is that it is said to combine characteristics from both public and private organisations, combining the best of both worlds. However, the popularity of internal contracts was short-lived, and just a few years later it seemed to be out of fashion. A few municipalities, however, constitute examples of where internal contracts were subscribed to and supported for a longer period of time. These municipalities showed that theories relating to fashions for ideas, and what causes fluctuations in fashions, are not sufficient to explain variations in the lifecycles of ideas. There are variations in the life cycles of fashionable ideas, with some seeming to disappear as soon as they arise while others remain influential over a longer period of time. Why is this? The popularity and use of ideas is not only the result of gaining legitimacy in an institutional environment, as has long been suggested, but also the result of individual interpretations of ideas, in the context in which they are introduced. Ideas are changed and modified, or translated, as they travel in and between organisations. In turn, translations affect the ways in which ideas are perceived and whether or not they are considered legitimate and supported by the people who receive them. The fate of ideas thus lies in the hands of people, each of whom may accept, modify or deflect them, as well as add to them or let them drop. The study suggests a model for how the life-cycle of ideas can be understood based on how, by whom, when and where they are translated. It illustrates how (1) the receiver of ideas, (2) the carrier of the ideas and (3) characteristics assigned to ideas affect translations and thereby, whether their life-cycles are to become short or long. The study also highlights the fact that ideas are often revivals of earlier ideas rather than new ones, suggesting that ideas seldom die, but are instead given more or less attention in different times and spaces. In addition, in studying the process, not just the ups and downs in popularity, the study shows that what makes ideas come to life, and stay alive, is the result of continuous work. People need to be convinced on a continuous basis that ideas are attractive. Finally, the study contributes to further understanding institutionalisation. What affects translation also affects whether actions are repeated, and over time become taken for granted in an organisation.
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| 13. |
- Carlsson, Julia, et al.
(författare)
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Opportunites for Integrated Landscape Planning : the Broker, the Arena, the Tool
- 2017
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Ingår i: Landscape Online. - 1865-1542. ; 55, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- As an integrated social and ecological system, the forest landscape includes multiple values. The need for a landscape approach in land use planning is being increasingly advocated in research, policy and practice. This paper explores how institutional conditions in the forest policy and management sector can be developed to meet demands for a multifunctional landscape perspective. Departing from obstacles recognised in collaborative planning literature, we build an analytical framework which is operationalised in a Swedish context at municipal level. Our case illustrating this is Vilhelmina Model Forest, where actual barriers and opportunities for a multiple-value landscape approach are identified through 32 semi-structured interviews displaying stakeholders’ views on forest values, ownership rights and willingness to consider multiple values, forest policy and management premises, and collaboration. As an opportunity to overcome the barriers, we suggest and discuss three key components by which an integrated landscape planning approach could be realized in forest management planning: the need for a landscape coordinator (broker), the need for a collaborative forum (arena), and the development of the existing forest management plan into an advanced multifunctional landscape plan (tool).
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| 14. |
- Carlsson, Julia Sofia, et al.
(författare)
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Digitaliserat ekonomiskt bistånd – Konstruktioner av ”nya” relationer inom socialtjänsten
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport syftar till att belysa om, och i så fall hur, klienters tillgång till välfärdsservice förändras vid användningen av digitala verktyg inom socialtjänsten. Forskningsfrågan som guidar studien är: hur påverkas relationen mellan socialsekreterare och klient av införandet av digitala verktyg inom ekonomiskt bistånd?I studien undersöks socialsekreterares uppfattningar om sin relation till klienter i tre olika kommuner. Genom ett urval av tre kommuner som kommit olika långt i sitt digitaliseringsarbete öppnar studien upp för en jämförelse mellan socialsekreterarnas beskrivningar. I jämförelsen uppmärksammas skillnader mellan beskrivningar av relationen mellan socialsekreterare och klient. Genom att studera skillnader synliggörs om, och i så fall hur, digitala verktyg har en inverkan på relationen mellan socialsekreterare och klient.Valet att ställa relationen i fokus i studien grundar sig på att tidigare forskning pekar på att relationen mellan ”det offentliga” och invånare är central för invånares tillgång till välfärdsservice och förutsättning för offentligt stöd. I förlängningen blir därigenom studien en grund för att diskutera om och hur klienters tillgång till ekonomiskt bistånd förändras vid introduktionen av digitala verktyg och huruvida det finns en risk för ett digitalt utanförskap.Resultatet från studien visar att den arbetsdelning som följer av en digitalisering kan påverka till en ökad distans mellan socialsekreterare och klientklienter och att det med digitalisering följer en retorik som handlar om att mer ansvar bör läggas på enskilda medborgare. Det kan för den enskilda klienten leda till ett ökat ansvar över att driva det egna ärendet i relation till myndigheten och därigenom försämra klienters tillgång till välfärdsservice för klienter. Dock behöver inte så vara fallet. Studiens resultat visar samtidigt att socialsekreterare och ekonomisekreterare till stor del betraktar de digitala verktygen som ett komplement, som breddar tillgängligheten och att medvetenheten om risker för ett digitalt utanförskap ger en lyhördhet inför om klienter har behov av stöd. Med andra ord visar studien hur socialsekreterare och/eller ekonomisekreterare arbetar för att kompensera för teknikens brister.
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| 15. |
- Carlsson, Julia Sofia
(författare)
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Exploring the many tales behind success : understanding translations of the “intrapreneurships” management fashion as editing processes
- 2021
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Ingår i: Qualitative research in organization and management. - : Emerald Group Holdings Ltd.. - 1746-5648 .- 1746-5656.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The paper explores a management fashion within the Swedish Public Sector called intrapreneurships. Intrapreneurships became popular during a period of public debate on what forms of organizing are most suitable for the production of welfare. However, while the popularity of the model was short-lived, a few municipalities nevertheless constitute examples of where it was supported for a longer period. The aim of this paper is to investigate how the model became continuously legitimate having lost its appeal elsewhere.Design/methodology/approach: The paper comprises a longitudinal analysis of two municipalities. Field-material was collected through qualitative methods including interviews (35 interviews, 42 interviewees) and document analysis.Findings: The results draw attention to how management fashions become enduring. The metaphor of translation highlights how different professional actors in a local setting apply editing rules, and how they constitute work acquired for continuous translation of the model in order to make it legitimate, disseminated and supported. The study draws particular attention to the large number of actors involved in the editing process.Originality/value: Besides an extended understanding of management concepts, to explain the anomaly of a long-standing management fashion, the paper illustrates the importance of acknowledging editing as processes and not process. A key notion in why intrapreneurships became legitimate is that professional actors edited the model differently in order to satisfy their desires and needs. This contradicts the more common case study design in translation studies, which seeks a unitary translation process, in a single local setting. © 2021, Julia Sofia Carlsson.
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| 16. |
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| 17. |
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| 18. |
- Eleftherohorinou, Hariklia, et al.
(författare)
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famCNV: copy number variant association for quantitative traits in families.
- 2011
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Ingår i: Bioinformatics (Oxford, England). - : Oxford University Press (OUP). - 1367-4811 .- 1367-4803. ; 27:13, s. 1873-5
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Tidskriftsartikel (refereegranskat)abstract
- A program package to enable genome-wide association of copy number variants (CNVs) with quantitative phenotypes in families of arbitrary size and complexity. Intensity signals that act as proxies for the number of copies are modeled in a variance component framework and association with traits is assessed through formal likelihood testing. AVAILABILITY AND IMPLEMENTATION: The Java package is made available at www.imperial.ac.uk/medicine/people/m.falchi/. CONTACT: m.falchi@imperial.ac.uk.
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| 19. |
- Elmberg, Maria, et al.
(författare)
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Increased Risk of Arthropathies and Joint Replacement Surgery in Patients With Genetic Hemochromatosis: A Study of 3,531 Patients and Their 11,794 First-Degree Relatives
- 2013
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 65:5, s. 678-685
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Tidskriftsartikel (refereegranskat)abstract
- Objective Genetic hemochromatosis (GH) is an autosomal recessive disease in individuals of Northern and Western European descent. Heterozygosity for the C282Y mutation is common (620%). Arthropathy is one of the few complications of GH suggested not to be associated with iron body stores; synovial iron deposition remains in iron-depleted patients. Previous studies suggest an elevated prevalence of clinical and radiographic signs of arthropathy in patients with GH, and 2 smaller studies suggest a possibly elevated risk of joint replacement surgery, but more mixed results are shown regarding risks with HFE genotype. We therefore assessed the risks of arthropathy and joint replacement surgery in patients with GH and in their first-degree relatives (FDRs). Methods We performed a population-based cohort study of 3,531 patients with GH and of their 11,794 FDRs (assumed to be heterozygous for the C282Y mutation) using nationwide Swedish population-based health and census registers. Hazard ratios (HRs) of arthropathies and joint replacement surgeries among patients and their FDRs (versus the general population) were assessed using Cox regression. Results Between 1997 and 2005, 406 of 3,531 patients were reported/hospitalized with any noninfectious arthropathies, including osteoarthritis, corresponding to an HR of 2.38 (95% confidence interval [95% CI] 2.142.64). Patients were also at increased risk of hip replacement (HR 2.77, 95% CI 2.273.38) and knee replacement (HR 2.14, 95% CI 1.582.88) surgery. Among the 11,794 FDRs (patients excluded), we found no increased risk of any of the joint morbidities. Conclusion Patients with GH, but not their FDRs, are at increased risk of arthropathies, including the need for joint replacement surgery.
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| 20. |
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| 21. |
- Hjärpe, Teres, et al.
(författare)
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Digitalized Social Services : Formation of "new" street-level relations and professional compensation
- 2024
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Ingår i: ; , s. 1-21
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper investigates social workers' perceptions of their relationships with clients across three Swedish different municipalities. By selecting three municipalities at varying stages of digitalization, the study highlights differences in the descriptions of the relationship between social workers and clients, shedding light on whether, and if so, how, digital tools influence this relationship.The decision to focus on the relationship in the study is based on previous research indicating that the relationship between the social worker and the client is central to clients´access to welfare services and the provision of public support. Consequently, the study serves as a basis for discussing whether and how clients' access to financial assistance changes with the introduction of digital tools and whether there is a risk of digital exclusion.The results of the study indicate that the division of labor resulting from digitalization can lead to increased distance between social workers and clients, and that digitalization entails a rhetoric suggesting that more responsibility should be placed on individual citizens. This may result in increased responsibility for individual clients to manage their own cases in relation to the authorities, potentially impairing clients' access to welfare services. However, this may not necessarily be the case. The study's results also show that social workers and financial administrators largely view digital tools as a complement, expanding accessibility, and that awareness of the risks of digital exclusion fosters sensitivity to whether clients need support. In other words, the study demonstrates how social workers and/or financial administrators work to compensate for the shortcomings of technology.
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| 22. |
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| 23. |
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| 24. |
- Lagerqvist, Nina, et al.
(författare)
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Evaluation of 11 SARS-CoV-2 antibody tests by using samples from patients with defined IgG antibody titers
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the performance of 11 SARS-CoV-2 antibody tests using a reference set of heat-inactivated samples from 278 unexposed persons and 258 COVID-19 patients, some of whom contributed serial samples. The reference set included samples with a variation in SARS-CoV-2 IgG antibody titers, as determined by an in-house immunofluorescence assay (IFA). The five evaluated rapid diagnostic tests had a specificity of 99.0% and a sensitivity that ranged from 56.3 to 81.6% and decreased with low IFA IgG titers. The specificity was > 99% for five out of six platform-based tests, and when assessed using samples collected ≥ 22 days after symptom onset, two assays had a sensitivity of > 96%. These two assays also detected samples with low IFA titers more frequently than the other assays. In conclusion, the evaluated antibody tests showed a heterogeneity in their performances and only a few tests performed well with samples having low IFA IgG titers, an important aspect for diagnostics and epidemiological investigations.
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| 25. |
- Lidestav, Gun, et al.
(författare)
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Models of Representation and Participation in Model Forests: Dilemmas and Implications for Networked Forms of Environmental Governance Involving Indigenous People
- 2013
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Ingår i: Environmental Policy and Governance. - : Wiley. - 1756-932X. ; 23, s. 161-176
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Tidskriftsartikel (refereegranskat)abstract
- Our study of two Model Forests illustrates the complex nature of representation in governance networks, in which different traditions of governance, persistent political disagreement and historical adversaries work together to achieve some goal. Using Pitkin's (1967) models of representation, we examined the role of social practices in giving meaning to representation in two model forests in Canada and in Sweden. Two normative models of representation (e.g., trustee and delegate) guided our interpretation of the enactment of representation in the two model forests mainly by highlighting how such models may be culturally biased-resulting in dilemmas of governance for actors that do not ascribe such meanings to representation. These insights led to a greater appreciation for the significance of politics in the enactment of representation, especially with regards to the political aspirations that motivate participatory and deliberative environmental governance. Our analysis suggests that the legitimacy and effectiveness of natural resource and environmental governance networks are affected by the rules structuring participation and deliberation, which are substantiated in social practices of representation in these networks. Our work further suggests that the analysis of representation in network forms of governance cannot be separated from an analysis of the politics of competing interests, especially whose interests are advanced and how these interests are given voice in steering environmental governance. Copyright (c) 2013 John Wiley & Sons, Ltd and ERP Environment
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| 26. |
- Lienard, Julia, et al.
(författare)
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A Murine Mycobacterium marinum Infection Model for Longitudinal Analyses of Disease Development and the Inflammatory Response
- 2023. - 2
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Ingår i: Bacterial Pathogenesis : Methods and Protocols - Methods and Protocols. - 1064-3745 .- 1940-6029. - 9781071632451 - 9781071632437 ; 2674, s. 313-326
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Bokkapitel (refereegranskat)abstract
- Mycobacterial infections, including tuberculosis, are a major health problem globally. Prevention and treatments of tuberculosis are challenging due to the poor efficacy of the current vaccine and the emergence of drug-resistant strains. Therefore, it is critical to increase our basic understanding of mycobacterial virulence strategies as well as the host immune response during infection in the complex in vivo setting. While existing infection models provide valuable tools for investigating mycobacterial pathogenesis, they also exhibit limitations that can be addressed by the development of complementary models. Here we describe recent advances to the murine Mycobacterium marinum infection model, in which the bacteria produce a local infection restricted to the tail tissue. The M. marinum model has the advantage of mimicking some of the key hallmarks of human tuberculosis not replicated in the conventional murine Mycobacterium tuberculosis model, such as the formation of granulomas with central caseating necrosis and the spontaneous development of a latency-like stage. Moreover, the model is non-lethal and enables longitudinal analysis of disease development in live animals. In this chapter, we report protocols to prepare infected tissue samples for detailed and quantitative analysis of the immune response by flow cytometry, immunofluorescence microscopy, RT-qPCR, ELISA, and Western blot, as well as for the analysis of bacterial load and localization.
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| 27. |
- Lienard, Julia, et al.
(författare)
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ESX-1 exploits type I IFN-signalling to promote a regulatory macrophage phenotype refractory to IFNγ-mediated autophagy and growth restriction of intracellular mycobacteria
- 2016
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814. ; 18:10, s. 1471-1485
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Tidskriftsartikel (refereegranskat)abstract
- Summary: The ability of macrophages to eradicate intracellular pathogens is normally greatly enhanced by IFNγ, a cytokine produced mainly after onset of adaptive immunity. However, adaptive immunity is unable to provide sterilizing immunity against mycobacteria, suggesting that mycobacteria have evolved virulence strategies to inhibit the bactericidal effect of IFNγ-signalling in macrophages. Still, the host-pathogen interactions and cellular mechanisms responsible for this feature have remained elusive. We demonstrate that the ESX-1 type VII secretion systems of Mycobacterium tuberculosis and Mycobacteriummarinum exploit type I IFN-signalling to promote an IL-12low/IL-10high regulatory macrophage phenotype characterized by secretion of IL-10, IL-27 and IL-6. This mechanism had no impact on intracellular growth in the absence of IFNγ but suppressed IFNγ-mediated autophagy and growth restriction, indicating that the regulatory phenotype extends to function. The IFNγ-refractory phenotype was partly mediated by IL-27-signalling, establishing functional relevance for this downstream cytokine. These findings identify a novel macrophage-modulating function for the ESX-1 secretion system that may contribute to suppress the efficacy of adaptive immunity and provide mechanistic insight into the antagonistic cross talk between type I IFNs and IFNγ in mycobacterial infection.
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| 28. |
- Lienard, Julia, et al.
(författare)
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Intragranuloma Accumulation and Inflammatory Differentiation of Neutrophils Underlie Mycobacterial ESX-1-Dependent Immunopathology
- 2023
-
Ingår i: mBio. - 2161-2129. ; 14:2
-
Tidskriftsartikel (refereegranskat)abstract
- The conserved ESX-1 type VII secretion system is a major virulence determinant of pathogenic mycobacteria, including Mycobacterium tuberculosis and Mycobacterium marinum. ESX-1 is known to interact with infected macrophages, but its potential roles in regulating other host cells and immunopathology have remained largely unexplored. Using a murine M. marinum infection model, we identify neutrophils and Ly6C +MHCII + monocytes as the main cellular reservoirs for the bacteria. We show that ESX-1 promotes intragranuloma accumulation of neutrophils and that neutrophils have a previously unrecognized required role in executing ESX-1-mediated pathology. To explore if ESX-1 also regulates the function of recruited neutrophils, we performed a single-cell RNA-sequencing analysis that indicated that ESX-1 drives newly recruited uninfected neutrophils into an inflammatory phenotype via an extrinsic mechanism. In contrast, monocytes restricted the accumulation of neutrophils and immunopathology, demonstrating a major host-protective function for monocytes specifically by suppressing ESX-1-dependent neutrophilic inflammation. Inducible nitric oxide synthase (iNOS) activity was required for the suppressive mechanism, and we identified Ly6C +MHCII + monocytes as the main iNOS-expressing cell type in the infected tissue. These results suggest that ESX-1 mediates immunopathology by promoting neutrophil accumulation and phenotypic differentiation in the infected tissue, and they demonstrate an antagonistic interplay between monocytes and neutrophils by which monocytes suppress host-detrimental neutrophilic inflammation. IMPORTANCE The ESX-1 type VII secretion system is required for virulence of pathogenic mycobacteria, including Mycobacterium tuberculosis. ESX-1 interacts with infected macrophages, but its potential roles in regulating other host cells and immunopathology have remained largely unexplored. We demonstrate that ESX-1 promotes immunopathology by driving intragranuloma accumulation of neutrophils, which upon arrival adopt an inflammatory phenotype in an ESX-1-dependent manner. In contrast, monocytes limited the accumulation of neutrophils and neutrophil-mediated pathology via an iNOS-dependent mechanism, suggesting a major host-protective function for monocytes specifically by restricting ESX-1-dependent neutrophilic inflammation. These findings provide insight into how ESX-1 promotes disease, and they reveal an antagonistic functional relationship between monocytes and neutrophils that might regulate immunopathology not only in mycobacterial infection but also in other infections as well as in inflammatory conditions and cancer.
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| 29. |
- Lienard, Julia, et al.
(författare)
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Murine Mycobacterium marinum infection as a model for tuberculosis
- 2017
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Ingår i: Methods in Molecular Biology. - New York, NY : Springer New York. - 1064-3745. ; 1535, s. 301-315
-
Bokkapitel (refereegranskat)abstract
- Mycobacteria are a major human health problem globally. Regarding tuberculosis the situation is worsened by the poor efficacy of current vaccine regimens and by emergence of drug-resistant strains (Manjelievskaia J et al, Trans R Soc Trop Med Hyg 110: 110, 2016; Pereira et al., Lancet Infect Dis 12:300–306, 2012; http://www.who.int/tb/publications/global_report/en/) undermining both disease-prevention and available treatments. Thus, increased basic understanding of mycobacterial—and particularly Mycobacterium tuberculosis —virulence strategies and pathogenesis is of great importance. To this end several in vivo infection models are available (Guirado and Schlesinger, Front Immunol 4:98, 2013; Leung et al., Eur J Immunol 43:2246–2254, 2013; Patel et al., J Lab Physicians 3:75–79, 2011; van Leeuwen et al., Cold Spring Harb Perspect Med 5:a018580, 2015). While these models all have their merits they also exhibit limitations, and none perfectly mimics all aspects of human tuberculosis. Thus, there is a need for multiple models that may complement each other, ultimately allowing us to gain true insight into the pathogenesis of mycobacterial infections. Here, we describe a recently developed mouse model of Mycobacterium marinum infection that allows kinetic and quantitative studies of disease progression in live animals [8]. Notably, this model exhibits features of human tuberculosis not replicated in M. tuberculosis infected mice, and may provide an important complement to the field. For example, granulomas in the M. marinum model develop central caseating necrosis (Carlsson et al., PLoS Pathog 6:e1000895, 2010), a hallmark of granulomas in human tuberculosis normally not replicated in murine M. tuberculosis infection. Moreover, while tuberculosis is heterogeneous and presents with a continuum of active and latent disease, M. tuberculosis infected mice essentially lack this dynamic range and do not replicate latency (Guirado and Schlesinger, Front Immunol 4:98, 2013; Patel et al., J Lab Physicians 3(2):75–79, 2011). In contrast, M. marinum infected mice may naturally develop latency, as suggested by reduced inflammation and healing of the diseased tissue while low numbers of bacteria persist in granulomatous lesions (Carlsson et al., PLoS Pathog 6:e1000895, 2010). Thus, infection with M. marinum may offer a unique murine model for studying granuloma formation as well as latency— and possibly also for studies of disease-reactivation. In addition to the in vivo model, we describe infection of bone marrow-derived murine macrophages, an in vitro platform enabling detailed mechanistic studies of host-pathogen interactions occurring in the principal host target cell for pathogenic mycobacteria.
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| 30. |
- Lienard, Julia, et al.
(författare)
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The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 117:2, s. 1160-1166
-
Tidskriftsartikel (refereegranskat)abstract
- Following mycobacterial entry into macrophages the ESX-1 type VII secretion system promotes phagosomal permeabilization and type I IFN production, key features of tuberculosis pathogenesis. The current model states that the secreted substrate ESAT-6 is required for membrane permeabilization and that a subsequent passive leakage of extracellular bacterial DNA into the host cell cytosol is sensed by the cyclic GMP-AMP synthase (cGAS) and stimulator of IFN genes (STING) pathway to induce type I IFN production. We employed a collection of Mycobacterium marinum ESX-1 transposon mutants in a macrophage infection model and show that permeabilization of the phagosomal membrane does not require ESAT-6 secretion. Moreover, loss of membrane integrity is insufficient to induce type I IFN production. Instead, type I IFN production requires intact ESX-1 function and correlates with release of mitochondrial and nuclear host DNA into the cytosol, indicating that ESX-1 affects host membrane integrity and DNA release via genetically separable mechanisms. These results suggest a revised model for major aspects of ESX-1-mediated host interactions and put focus on elucidating the mechanisms by which ESX-1 permeabilizes host membranes and induces the type I IFN response, questions of importance for our basic understanding of mycobacterial pathogenesis and innate immune sensing.
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| 31. |
- Lindblom, Sebastian, et al.
(författare)
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Lifestyle counseling in patients with hypertension in primary health care and its association with antihypertensive pharmacotherapy
- 2024
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Ingår i: The Journal of Clinical Hypertension. - 1524-6175 .- 1751-7176.
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to investigate differences in hypertensive- and cardio-preventive pharmacotherapy depending on if patients with hypertension received lifestyle counseling or not, including the difference between men and women. Data from the Region Stockholm VAL database was used to identify all patients with a hypertension diagnosis and had visited a primary health care center within the past five years. Data included registered diagnoses, pharmacotherapy, and codes for lifestyle counseling. Logistic regression adjusted for age and comorbidity (diabetes, stroke, coronary heart disease, atrial fibrillation, gout, obesity, heart failure) was used, presenting results as odds ratios (OR) with 99% confidence interval (CI). The study included 130,030 patients with hypertension; 63,402 men and 66,628 women. Patients receiving recommended lifestyle counseling were more frequently treated with three or more hypertensive drugs: women OR 1.38 (1.31, 1.45) and men = 1.36 (1.30, 1.43); certain drug classes: calcium antagonists: women 1.09 (1.04, 1.14) and men 1.11 (1.06, 1.16); thiazide diuretics: women 1.26 (1.20, 1.34) and men 1.25 (1.19, 1.32); and aldosterone antagonists: women 1.25 (1.12, 1.41) and men 1.49 (1.34, 1.65). Patients receiving recommended level of lifestyle counseling with concomitant coronary heart disease, atrial fibrillation, diabetes, or stroke were more frequently treated with statins than those who did not. Further, recommended lifestyle counseling was significantly associated with anticoagulant treatment in patients with atrial fibrillation. Lifestyle counseling according to recommendations in national guidelines was significantly associated with a more thorough pharmacological treatment of hypertension, statins, and antithrombotic drugs as well as anticoagulants, in both men and women.
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| 32. |
- Mansour Aly, Dina, et al.
(författare)
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Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53, s. 1534-1542
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes has been reproducibly clustered into five subtypes with different disease progression and risk of complications; however, etiological differences are unknown. We used genome-wide association and genetic risk score (GRS) analysis to compare the underlying genetic drivers. Individuals from the Swedish ANDIS (All New Diabetics In Scania) study were compared to individuals without diabetes; the Finnish DIREVA (Diabetes register in Vasa) and Botnia studies were used for replication. We show that subtypes differ with regard to family history of diabetes and association with GRS for diabetes-related traits. The severe insulin-resistant subtype was uniquely associated with GRS for fasting insulin but not with variants in the TCF7L2 locus or GRS reflecting insulin secretion. Further, an SNP (rs10824307) near LRMDA was uniquely associated with mild obesity-related diabetes. Therefore, we conclude that the subtypes have partially distinct genetic backgrounds indicating etiological differences.
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| 33. |
- Movert, Elin, et al.
(författare)
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Streptococcal M protein promotes IL-10 production by cGAS-independent activation of the STING signaling pathway
- 2018
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7374 .- 1553-7366. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- From an evolutionary point of view a pathogen might benefit from regulating the inflammatory response, both in order to facilitate establishment of colonization and to avoid life-threatening host manifestations, such as septic shock. In agreement with this notion Streptococcus pyogenes exploits type I IFN-signaling to limit detrimental inflammation in infected mice, but the host-pathogen interactions and mechanisms responsible for induction of the type I IFN response have remained unknown. Here we used a macrophage infection model and report that S. pyogenes induces anti-inflammatory IL-10 in an M protein-dependent manner, a function that was mapped to the B- and C-repeat regions of the M5 protein. Intriguingly, IL-10 was produced downstream of type I IFN-signaling, and production of type I IFN occurred via M protein-dependent activation of the STING signaling pathway. Activation of STING was independent of the cytosolic double stranded DNA sensor cGAS, and infection did not induce detectable release into the cytosol of either mitochondrial, nuclear or bacterial DNA–indicating DNA-independent activation of the STING pathway in S. pyogenes infected macrophages. These findings provide mechanistic insight concerning how S. pyogenes induces the type I IFN response and identify a previously unrecognized macrophage-modulating role for the streptococcal M protein that may contribute to curb the inflammatory response to infection.
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| 34. |
- Nafees, Zanib, et al.
(författare)
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Adaptation, Translation, and Validation of a Patient-Reported Experience Measure for Children and Young People for the Canadian Context
- 2024
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Ingår i: Journal of Pediatric Surgery. - : Elsevier. - 0022-3468 .- 1531-5037. ; 59:5, s. 810-817
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patient-reported experience measures (PREMs) evaluate children's and young people's (CYP) perceptions of care. An important PREM developed with and for children was created in London, UK. Given the absence of similar North American instruments, we aimed to adapt, translate, and linguistically validate this instrument for use in a Canadian pediatric outpatient setting.METHODS: A qualitative design was used, involving CYP and their parents/caregivers. Phase 1 entailed the English survey adaptation using think-aloud testing, revision, and cognitive testing. Phase 2 involved translation into French, revision and back-translation, and cognitive testing. Phase 3 encompassed a cross-validation of the English and French versions of the adapted instrument.RESULTS: Fifty-five children in 3 age groups (8-11y, 12-13y, 14-16y) participated in creating the Canadian PREM. In Phases 1 and 2, 41 children participated in reviewing and updating specific questions in the instrument, resulting in adjustments and revisions based on their feedback. In Phase 3, 14 bilingual children linguistically validated the PREM instrument.CONCLUSIONS: This study reports the development of the first Canadian PREM specifically tailored to children. By incorporating the perspectives and preferences of CYP in clinical practice, this approach has the potential to amplify the delivery of patient-centered care for this vulnerable population and ensure that the needs and voices of CYP are acknowledged.LEVEL OF EVIDENCE: V, Therapeutic.
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| 35. |
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| 36. |
- Nätt, Daniel, et al.
(författare)
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Human sperm displays rapid responses to diet
- 2019
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Ingår i: PLoS biology. - San Francisco, CA United States : PUBLIC LIBRARY SCIENCE. - 1544-9173 .- 1545-7885. ; 17:12
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Tidskriftsartikel (refereegranskat)abstract
- The global rise in obesity and steady decline in sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows that paternal diet can affect offspring metabolic health in a process involving sperm tRNA-derived small RNA (tsRNA). Here, we report that human sperm are acutely sensitive to nutrient flux, both in terms of sperm motility and changes in sperm tsRNA. Over the course of a 2-week diet intervention, in which we first introduced a healthy diet followed by a diet rich in sugar, sperm motility increased and stabilized at high levels. Small RNA-seq on repeatedly sampled sperm from the same individuals revealed that tsRNAs were up-regulated by eating a high-sugar diet for just 1 week. Unsupervised clustering identified two independent pathways for the biogenesis of these tsRNAs: one involving a novel class of fragments with specific cleavage in the T-loop of mature nuclear tRNAs and the other exclusively involving mitochondrial tsRNAs. Mitochondrial involvement was further supported by a similar up-regulation of mitochondrial rRNA-derived small RNA (rsRNA). Notably, the changes in sugar-sensitive tsRNA were positively associated with simultaneous changes in sperm motility and negatively associated with obesity in an independent clinical cohort. This rapid response to a dietary intervention on tsRNA in human sperm is attuned with the paternal intergenerational metabolic responses found in model organisms. More importantly, our findings suggest shared diet-sensitive mechanisms between sperm motility and the biogenesis of tsRNA, which provide novel insights about the interplay between nutrition and male reproductive health.
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| 37. |
- Orlovska, Julia, 1977, et al.
(författare)
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Design and implementation of driver coach application for pilot assist: A first validation study
- 2024
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Ingår i: Transportation Research Interdisciplinary Perspectives. - 2590-1982. ; 25
-
Tidskriftsartikel (refereegranskat)abstract
- This article discusses the importance of driver understanding and trust in Advanced Driver-Assistance Systems (ADAS) and proposes a framework for a personalized driver coaching system called Driver Coach, focusing on the Volvo Pilot Assist (PA) function. Despite the widespread adoption of ADAS, research indicates that many drivers have limited comprehension of ADAS functionality and limitations. Moreover, feedback-related factors play a crucial role in determining drivers’ proper use of ADAS. The article emphasizes the need for appropriate, continual feedback to enhance driver interaction with ADAS. Traditional methods, such as user manuals or supervised test drives, have limitations in effectively conveying critical information and facilitating driver adaptation. To address these challenges, the proposed Driver Coach app provides personalized, real-time recommendations to drivers based on their individual needs and understanding of both the system and driving context. The app was tested in a field trial involving 17 drivers over a four-month period, and the results regarding the logic design verification and the impact of the Driver Coach app on PA usage are presented. The findings highlight the potential of personalized, context-aware coaching systems to improve driver understanding and usage of ADAS.
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| 38. |
- Proletov, Ian, et al.
(författare)
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Primary and secondary glomerulonephritides 1.
- 2014
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
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Tidskriftsartikel (refereegranskat)
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| 39. |
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| 40. |
- Singh, Kailash, et al.
(författare)
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Interleukin-35 administration counteracts established murine type 1 diabetes - possible involvement of regulatory T cells
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- The anti-inflammatory cytokine IL-35 is produced by regulatory T (Treg) cells to suppress autoimmune and inflammatory responses. The role of IL-35 in type 1 diabetes (T1D) remains to be answered. To elucidate this, we investigated the kinetics of Treg cell response in the multiple low dose streptozotocin induced (MLDSTZ) T1D model and measured the levels of IL-35 in human T1D patients. We found that Treg cells were increased in MLDSTZ mice. However, the Treg cells showed a decreased production of anti-inflammatory (IL-10, IL-35, TGF-beta) and increased pro-inflammatory (IFN-gamma, IL-2, IL-17) cytokines, indicating a phenotypic shift of Treg cells under T1D condition. IL-35 administration effectively both prevented development of, and counteracted established MLDSTZ T1D, seemingly by induction of Eos expression and IL-35 production in Treg cells, thus reversing the phenotypic shift of the Treg cells. IL-35 administration reversed established hyperglycemia in NOD mouse model of T1D. Moreover, circulating IL-35 levels were decreased in human T1D patients compared to healthy controls. These findings suggest that insufficient IL-35 levels play a pivotal role in the development of T1D and that treatment with IL-35 should be investigated in treatment of T1D and other autoimmune diseases.
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| 41. |
- Stedt, Johanna, et al.
(författare)
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Micro-scale spatial preference and temporal cyclicity linked to foraging in harbour porpoises
- 2023
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Ingår i: Marine Ecology - Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 708, s. 143-161
-
Tidskriftsartikel (refereegranskat)abstract
- Habitat heterogeneity is a crucial driver for species distribution across scales. Harbour porpoise Phocoena phocoena basin-wide distribution is linked to prey availability, and small-scale (kilometres to tens of kilometres) differences in distribution are prevalent. However, information on porpoise distribution and foraging-behaviour variations on a micro-scale (~100 m to kilometres) is limited. To monitor harbour porpoise distribution and foraging activity on a micro-scale, we deployed passive acoustic dataloggers, logging porpoise acoustic activity at 6 sites in a small, high porpoise-density area in southern Sweden. Data were collected for almost a year, giving detailed time series on porpoise activity. The time series were analysed using dynamic time warping to compare activity patterns between sites. Large differences were found between sites separated by only a few hundred meters, indicating micro-scale spatial preference. Spectral analysis for temporal cyclicity in activity revealed a dominant peak for 24 h cycles with higher activity at night for all sites. All sites also had a second peak for 29.5 d, linked to the lunar cycle with higher activity during full moon. Activity was overall highest during autumn and winter (September-December). Spatial and temporal patterns were linked to foraging, showing a positive correlation between porpoise presence and the percent of time present with detected foraging. The study demonstrates that harbour porpoise spatial distribution on a micro-scale should be considered in e.g. behavioural, management and conservation studies and actions. In addition, we show that time series statistical methodology is informative and appropriate for analysis of acoustic temporal data.
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| 42. |
- Söderström, Hanna, et al.
(författare)
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Compliance to a Gluten-Free Diet in Swedish Children with Type 1 Diabetes and Celiac Disease
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Children with type 1 diabetes (T1D) are at increased risk of celiac disease (CD). The replacement of insulin in T1D, and the exclusion of gluten in CD, are lifelong, burdensome treatments. Compliance to a gluten-free diet (GFD) in children with CD is reported to be high, while compliance in children with both diseases has scarcely been studied. To examine compliance to a GFD in children with both T1D and CD, we analyzed tissue transglutaminase IgA-antibodies (tTGA). Moreover, associations between compliance and age, sex, glycemic control, ketoacidosis (DKA), body mass index (BMI), and time of CD diagnosis were investigated. Of the 743 children diagnosed with T1D in southern Sweden between 2005 and 2012, 9% were also diagnosed with CD. Of these, 68% showed good compliance to a GFD, 18% showed intermediate compliance, and 14% were classified as non-compliant. Higher age, poorer HbA1c, and more DKAs were significantly (p < 0.05) associated with poorer compliance. In conclusion, we found that compliance to a GFD in children with T1D and CD is likely be lower than in children with CD only. Our results indicate that children with both T1D and CD could need intensified dietary support and that older children and children with poor metabolic control are especially vulnerable subgroups.
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| 43. |
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| 44. |
- Thorngren, Julia, 1993-
(författare)
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Transplantation of stem cell-derived islets as a treatment for type 1 diabetes
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes (T1D) is an autoimmune disease that leads to an immune attack on insulin-producing beta cells, necessitating lifelong insulin therapy. For individuals with brittle diabetes and poor metabolic control, the option of pancreatic human islet transplantation exists. However, the shortage of organ donors and the need for life-long immune suppressive agents pose significant challenges. Stem cell-derived islets (SC-islets) present a promising alternative for diabetes treatment. This thesis explores the differentiation and transplantation of SC-islets as a treatment for diabetes. In paper I, three months post-transplantation, the ingrowth of recipient blood vessels and the neural density was higher in SC-islet grafts compared to human islet grafts. Furthermore, there was a higher tendency of blood flow, whereas the oxygenation was twice as high in SC-islet grafts. Both transplanted SC-islets and human islets had formation of amyloid depositions, which can affect the long-term survival and function of transplanted cells. In paper II, a humanized mouse model transplanted with SC-islets or human islets was validated. Transplanted SC-islets or human islets were not completely rejected 11 days after injection with human peripheral blood mononuclear cells (PBMCs). In vivo imaging and flow cytometry confirmed the presence of injected human immune cells, demonstrating an effective model for studying the human immune responses of allogeneically transplanted islets or SC-islets. In paper III, positron emission tomography (PET) imaging, using the DGCR2 affibody, for monitoring transplanted beta cells revealed successful binding to SC-islets and human islets in vitro. PET imaging in vivo demonstrated successful detection of the affibody in transplanted SC-islets. Although, the affibody could be optimized since the signal vanished 30 min after administration. However, DGCR2 remains a promising marker for SC-islet imaging. In paper IV, nanofiltration with a virus clearance filter paper during SC-islet differentiation was evaluated. Filter SC-islets expressed essential markers for beta cells during differentiation in comparable amounts as the control. The filtered SC-islets demonstrated physiological insulin-releasing function similar to that of the control. Nanofiltration did not seem to affect the differentiation of SC-islets. In conclusion, transplantation of SC-islets is a promising future treatment for diabetes, however, long-term effects need to be evaluated.
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| 45. |
- Wallin, Ida, et al.
(författare)
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Envisioning future forested landscapes in Sweden - Revealing local-national discrepancies through participatory action research
- 2016
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Ingår i: Forest Policy and Economics. - : Elsevier BV. - 1389-9341 .- 1872-7050. ; 73, s. 25-40
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Tidskriftsartikel (refereegranskat)abstract
- Governance of forested landscapes must account for multiple interests and perspectives through public and stakeholder participation. In the context of Swedish forestry, participation has mainly been implemented as a top-down venture, without adequate integration of all interests. Linking local interests to national policy-making through participatory action research and future-oriented methodologies has not yet been tried in Sweden. We develop and implement a participatory action research model with the objectives to (i) facilitate a discussion among local stakeholders about their common future in relation to their forested landscapes and, (ii) to connect the local level with the national, institutional level. First, local stakeholders are brought together to create commonly desired visions in case studies of two forested landscapes in Sweden. Second, national policy-makers are engaged in a discussion on how to achieve the locally-desired visions. The ability of the two-step participatory action research model to achieve these objectives is then evaluated based on norms of Communicative Action and criteria of participatory planning. The results demonstrate the positive opportunity to engage local stakeholders in a constructive discussion about their common future, but also show some practical constraints of participatory methods, in particular the risk of institutional authorities disregarding local knowledge and claims. (C) 2016 Elsevier B.V. All rights reserved.
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| 46. |
- Wändell, Per, et al.
(författare)
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A machine learning tool for identifying patients with newly diagnosed diabetes in primary care
- 2024
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Ingår i: Primary Care Diabetes. - 1751-9918 .- 1878-0210.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIM: It is crucial to identify a diabetes diagnosis early. Create a predictive model utilizing machine learning (ML) to identify new cases of diabetes in primary health care (PHC).METHODS: A case-control study utilizing data on PHC visits for sex-, age, and PHC-matched controls. Stochastic gradient boosting was used to construct a model for predicting cases of diabetes based on diagnostic codes from PHC consultations during the year before index (diagnosis) date and number of consultations. Variable importance was estimated using the normalized relative influence (NRI) score. Risks of having diabetes were calculated using odds ratios of marginal effects (ORME). Four groups by age and sex were studied, age-groups 35-64 years and ≥ 65 years in men and women, respectively.RESULTS: The most important predictive factors were hypertension with NRI 21.4-29.7 %, and obesity 4.8-15.2 %. The NRI for other top ten diagnoses and administrative codes generally ranged 1.0-4.2 %.CONCLUSIONS: Our data confirm the known risk patterns for predicting a new diagnosis of diabetes, and the need to test blood glucose frequently. To assess the full potential of ML for risk prediction purposes in clinical practice, future studies could include clinical data on life-style patterns, laboratory tests and prescribed medication.
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| 47. |
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