| 1. |
- Scott, Aaron M., et al.
(författare)
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Population scale proteomics enables adaptive digital twin modelling in sepsis
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Sepsis is one of the leading causes of mortality in the world. Currently, the heterogeneity of sepsis makes it challenging to determine the molecular mechanisms that define the syndrome. Here, we leverage population scale proteomics to analyze a well-defined cohort of 1364 blood samples taken at time-of-admission to the emergency department from patients suspected of sepsis. We identified panels of proteins using explainable artificial intelligence that predict clinical outcomes and applied these panels to reduce high-dimensional proteomics data to a low-dimensional interpretable latent space (ILS). Using the ILS, we constructed an adaptive digital twin model that accurately predicted organ dysfunction, mortality, and early-mortality-risk patients using only data available at time-of-admission. In addition to being highly effective for investigating sepsis, this approach supports the flexible incorporation of new data and can generalize to other diseases to aid in translational research and the development of precision medicine.Competing Interest StatementThe authors have declared no competing interest.Funding StatementL.M. is funded by the Swedish Research Council (grant number VR-2020-02419), the Wallenberg foundation (grant number 2016.0023) and Alfred Österlunds Foundation. J.M. is a Wallenberg academy fellow (KAW 2017.0271) and is also funded by the Swedish Research Council (Vetenskapsrådet, VR) (2019-01646 and 2018-05795), the Wallenberg foundation (KAW2016.0023, KAW2019.0353 and KAW2020.0299), and Alfred Österlunds Foundation. E.M. is funded by Wenner-Gren Foundation (FT2020-0003), the Crafoord Foundation, and the Swedish Society of Medicine (SLS-985287). F.K. is funded by Region Skåne ALF project and the Crafoord Foundation. A.L. is funded by the Swedish Research Council VR 2023-02707 and Region Skåne ALF project 2022-0146.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethical approval for the study was obtained from the Swedish National Ethics Committee (file numbers 2022-01454-01, 2014/741 and 2016/271).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesData produced in the present study are available upon reasonable request to the authors
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| 2. |
- Bernhardson, Britt-Marie, et al.
(författare)
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Sensations, symptoms, and then what? : Early bodily experiences prior to diagnosis of lung cancer
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer (LC) generally lacks unique core symptoms or signs. However, there are a multitude of bodily sensations that are often non-specific, not easily understood, and many times initially not recognized as indicative of LC by the affected person, which often leads to late diagnosis. In this international qualitative study, we inductively analyzed retrospective accounts of 61 people diagnosed with LC in Denmark, England and Sweden. Using the bodily sensations they most commonly spoke about (tiredness, breathlessness, pain, and cough), we constructed four sensation-based cases to understand the pre-diagnostic processes of reasoning and practice triggered by these key indicators of LC. We thereafter critically applied Hay's model of sensations to symptoms transformation, examining its central concepts of duration, disability and vulnerability, to support understanding of these processes. We found that while duration and disability are clearly relevant, vulnerability is more implicitly expressed in relation to perceived threat. Tiredness, even when of long duration and causing disability, was often related to normal aging, rather than a health threat. Regardless of duration, breathlessness was disturbing and threatening enough to lead to care-seeking. Pain varied by location, duration and degree of disability, and thus also varied in degree of threat perceived. Preconceived, but unmet expectations of what LC-related cough and pain would entail could cause delays by misleading participants; if cough lasted long enough, it could trigger health care contact. Duration, disability, and sense of threat, rather than vulnerability, were found to be relevant concepts for understanding the trajectory to diagnosis for LC among these participants. The process by which an individual, their family and health care providers legitimize sensations, allowing them to be seen as potential symptoms of disease, is also an essential, but varying part of the diagnostic processes described here.
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| 3. |
- Bundgaard, Louise, et al.
(författare)
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Effective protein extraction combined with data independent acquisition analysis reveals a comprehensive and quantifiable insight into the proteomes of articular cartilage and subchondral bone
- 2022
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 30:1, s. 137-146
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objectives of this study was to establish a sensitive and reproducible method to map the cartilage and subchondral bone proteomes in quantitative terms, and mine the proteomes for proteins of particular interest in the pathogenesis of osteoarthritis (OA). The horse was used as a model animal.DESIGN: Protein was extracted from articular cartilage and subchondral bone samples from three horses in triplicate by pressure cycling technology or ultrasonication. Digested proteins were analysed by data independent acquisition based mass spectrometry. Data was processed using a pre-established spectral library as reference database (FDR 1%).RESULTS: We identified to our knowledge the hitherto most comprehensive quantitative cartilage (1758 proteins) and subchondral bone (1482 proteins) proteomes in all species presented to date. Both extraction methods were sensitive and reproducible and the high consistency of the identified proteomes (>97% overlap) indicated that both methods preserved the diversity among the extracted proteins. Proteome mining revealed a substantial number of quantifiable cartilage and bone matrix proteins and proteins involved in osteogenesis and bone remodeling, including ACAN, BGN, PRELP, FMOD, COMP, ACP5, BMP3, BMP6, BGLAP, TGFB1, IGF1, ALP, MMP3, and collagens. A number of proteins, including COMP and TNN, were identified in different protein isoforms with potential unique biological roles.CONCLUSION: We have successfully developed two sensitive and reproducible non-species specific workflows enabling a comprehensive quantitative insight into the proteomes of cartilage and subchondral bone. This facilitates the prospect of investigating the molecular events at the osteochondral unit in the pathogenesis of OA in future projects.
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| 4. |
- Colliander, Helena, Filosofie doktor, 1977-, et al.
(författare)
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Folkhögskolans pedagogik och didaktik
- 2020. - 1
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Ingår i: Om folkhögskolan. - Lund : Studentlitteratur AB. - 9789144133300 ; , s. 113-135
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Går det att tala om en särskild pedagogik och didaktik för folkhögskolan? Vilket pedagogiskt och didaktiskt idégods kan ses i folkhögskolans framväxt och utveckling, samt i den samtida folkhögskolan? Vilka förutsättningar inverkar på folkhögskolans pedagogik och didaktik? I detta kapitel lyfter vi inledningsvis fram några pedagogiska och didaktiska idéer som successivt utvecklats inom folkhögskolan, för att sedan identifiera några tankelinjer i dagens folkhögskola. Slutligen tittar vi närmare på hur olika förutsättningar gör att det, trots en gemensam historisk utveckling och vissa gemensamma ideér, finns en stor didaktisk och pedagogisk variation.
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| 5. |
- Eriksen, Jaran, et al.
(författare)
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High adherence to the 'Wise List' treatment recommendations in Stockholm : a 15-year retrospective review of a multifaceted approach promoting rational use of medicines
- 2017
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Ingår i: BMJ Open. - London, UK : BMJ Publishing Group Ltd. - 2044-6055. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To present the 'Wise List' (a formulary of essential medicines for primary and specialised care in Stockholm Healthcare Region) and assess adherence to the recommendations over a 15-year period.DESIGN: Retrospective analysis of all prescription data in the Stockholm Healthcare Region between 2000 and 2015 in relation to the Wise List recommendations during the same time period.SETTING: All outpatient care in the Stockholm Healthcare Region.PARTICIPANTS: All prescribers in the Stockholm Healthcare Region.MAIN OUTCOME MEASURES: The number of core and complementary substances included in the Wise List, the adherence to recommendations by Anatomic Therapeutic Chemical (ATC) 1st level using defined daily doses (DDDs) adjusted to the DDD for 2015, adherence to recommendations over time measured by dispensed prescriptions yearly between 2002 and 2015.RESULTS: The number of recommended core substances was stable (175-212). Overall adherence to the recommendations for core medicines for all prescribers increased from 75% to 84% (2000 to 2015). The adherence to recommendations in primary care for core medicines increased from 80% to 90% (2005 to 2015) with decreasing range in practice variation (32% to 13%). Hospital prescriber adherence to core medicine recommendations was stable but increased for the combination core and complementary medicines from 77% to 88% (2007 to 2015). Adherence varied between the 4 therapeutic areas studied.CONCLUSIONS: High and increasing adherence to the Wise List recommendations was seen for all prescriber categories. The transparent process for developing recommendations involving respected experts and clinicians using strict criteria for handling potential conflicts of interests, feedback to prescribers, continuous medical education and financial incentives are possible contributing factors. High-quality evidence-based recommendations to prescribers, such as the Wise List, disseminated through a multifaceted approach, will become increasingly important and should be developed further to include recommendations and introduction protocols for new expensive medicines.
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| 6. |
- Folkersen, Lasse, et al.
(författare)
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Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis : results from the COMBINE study.
- 2016
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Ingår i: Molecular Medicine. - : Springer Science and Business Media LLC. - 1076-1551 .- 1528-3658. ; 22, s. 322-328
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results have been discrepant with few successful replications. Our objective was to build a biobank with DNA, RNA and protein measurements to test the claim that the current state-of-the-art precision medicine will benefit RA patients.METHODS: We collected 451 blood samples from 61 healthy individuals and 185 RA patients initiating treatment, before treatment initiation and at a 3 month follow-up time. All samples were subjected to high-throughput RNA sequencing, DNA genotyping, extensive proteomics and flow cytometry measurements, as well as comprehensive clinical phenotyping. Literature review identified 2 proteins, 52 single-nucleotide polymorphisms (SNPs) and 72 gene-expression biomarkers that had previously been proposed as predictors of TNF inhibitor response (∆DAS28-CRP).RESULTS: From these published TNFi biomarkers we found that 2 protein, 2 SNP and 8 mRNA biomarkers could be replicated in the 59 TNF initiating patients. Combining these replicated biomarkers into a single signature we found that we could explain 51% of the variation in ∆DAS28-CRP. This corresponds to a sensitivity of 0.73 and specificity of 0.78 for the prediction of three month ∆DAS28-CRP better than -1.2.CONCLUSIONS: The COMBINE biobank is currently the largest collection of multi-omics data from RA patients with high potential for discovery and replication. Taking advantage of this we surveyed the current state-of-the-art of drug-response stratification in RA, and identified a small set of previously published biomarkers available in peripheral blood which predicts clinical response to TNF blockade in this independent cohort.
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| 7. |
- Hallqvist, Anders, 1966-, et al.
(författare)
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Vad är en folkhögskola?
- 2020. - 1
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Ingår i: Om folkhögskolan. - Lund : Studentlitteratur AB. - 9789144133300 ; , s. 47-66
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Vad kännetecknar folkhögskolan? Hur kan folkhögskolornas verksamhet beskrivas? Vilka värderingar vill folkhögskolan arbeta för? Vilka aktuella tendenser kan iakttas och hur bemöter skolorna dessa? I detta kapitel försöker vi ge ett svar på frågan vad en folkhögskola är. Vi säger något om hur den en gång grundades, och hur den utvecklats över tid med avseende på grundläggande idéer, uppdrag och verksamhet. Men framför allt berättar vi om folkhögskolan i dag, hur den är organiserad och vilken verksamhet som äger rum på landets över 150 olika folkhögskolor.
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| 8. |
- Hallqvist, Anders, 1966-, et al.
(författare)
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Vad är en folkhögskola?
- 2020. - 1
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Ingår i: Om vuxenutbildning och vuxnas studier. - Lund : Studentlitteratur AB. - 9789144133294 ; , s. 121-140
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- I det här kapitlet ska vi ge ett svar på frågan vad en folkhögskola är. Vi kommer att beskriva skolformen och den verksamhet som bedrivs. Vi kommer att redogöra för hur skolorna är organiserade, hur de styrs och finansieras, vilka olika funktioner folkhögskolan fyller och vilka värderingar den vill arbeta för. Vi kommer också att diskutera några aktuella tendenser och utmaningar, och hur skolorna förhåller sig till dem.
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| 9. |
- Harlin, Eva-Marie, 1954-, et al.
(författare)
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Den bortglömda folkhögskolans potential
- 2020
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Ingår i: Perspektiv på skolans problem. - Lund : Studentlitteratur AB. - 9789144133898 ; , s. 333-347
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Vi vill i det här kapitlet visa varför andra utbildningsformer borde inspireras av folkhögskolan, varför den borde få större uppmärksamhet och varför det vore olyckligt om den också utvecklades i en riktning mot det vi redan har gott om i andra utbildningsformer.
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| 10. |
- Holmstedt, Louise
(författare)
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Evaluation of Sustainable Urban District Developments : The case of Stockholm Royal Seaport
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Urban sustainable development is now seen as one of the keys in the quest for a sustainable world and increased interest in developing sustainable urban districts has become an important feature of urban sustainability. However, if cities and their districts are to be part of this transition, it will be necessary to determine the state and progress of urban developments. Evaluation and follow-up activities must therefore be an integral part of modern sustainability work.This thesis investigated evaluation methods and strategies for determining progress towards sustainable urban district development. The Stockholm Royal Seaport district in Sweden was used as the research arena in studies based on urban metabolism theories, including a single case study approach, focus group interviews, the Framework for Strategic Sustainable Development and quantitative data analysis. The thesis main results can be summarised as follows.A structured frame for use in theory and practice can strengthen programme development and minimise the risk of built-in problems in environmental and sustainability plans for new urban districts. The proposed evaluation model for Stockholm Royal Seaport displayed strengths regarding core evaluation activities, such as communicating a strong vision and recognising continuity in the evaluation process. It displayed weaknesses as regards organisational structure and system boundaries. The proof-of-concept implementation of a Smart Urban Metabolism framework enabled real-time evaluation data on district scale to be generated and processed. The implementation process also led to identification of limitations in the framework, such as access to business sensitive data, failed integration of data streams and privacy concerns. Dynamic, high-resolution meter data can provide a higher degree of transparency in evaluation results and permit inclusion of all stakeholder groups in urban districts. The frequently used energy performance indicator kWh/m2 (Atemp) was shown to be an insufficient communication tool to mediate knowledge, due to conflation of consumption and construction parameters and the need for prior knowledge for full understanding.
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