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  • Sampa, Vasiliki
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of ALM.
    Intersecting Identities: A Computational Exploration of Gender and Race in The Guardian’s Political Coverage, 2017 – 20222024Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This study examines The Guardian’s portrayal of intersectional feminism, with a focus on gender and race, analysing how social movements, particularly Black Lives Matter, influence its political coverage. Arising from Kimberlé Crenshaw’s research in 1989, the concept of intersectionality underscores that individuals can undergo various dimensions of oppression or privilege simultaneously. The research employs a combination of quantitative and qualitative methods, including topic modeling, keyword frequency analysis, collocation analysis, and close reading, to analyse 647 political articles. The topic modeling provides the structural framework of the thesis, revealing twenty topics, while keywords frequency analysis emphasizes in nine keywords related to intersectional feminism and their prevalence. The collocation analysis examines “gender and “race”. Close reading is used for deeper examination at every step of the analysis. Despite theme variations, certain subjects like gender gap and gender identity consistently underscore their enduring significance. Observing spikes in coverage, especially post-2020 discussions related to Black Lives Matter, suggests an increased emphasis on themes that focus on diversity and racial justice. The sparingly use of “intersectionality”, hints at a disparity between the conceptual framework and its direct representation in The Guardian’s political articles.

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  • Ryding, Agnes
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Media and Communication Studies.
    Edenroth, Alice
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Media and Communication Studies.
    Influencers inom fast fashion: Påverkan på följares konsumtionsbeteende och miljömedvetenhet genom sociala medier: En kvalitativ studie om hur influencers på sociala medier påverkar sina följares uppfattning om, och konsumtionsbeteenden inom fast fashion-industrin.2024Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This qualitative study aims to examine the challenges of fast fashion consumption, encompassing a comprehensive examination of various factors and multifaceted dilemmas related to consumer choices. Clothing consumption serves more than just material needs, with today's society witnessing a strong connection between consumption and social norms, trends, and ideals, especially through social media. The choice of fashion consumption proves to be a complex issue in sustainability discussions. This complexity is heightened as social media influencers actively endorse and glamorize fast fashion products despite their well-known environmental consequences. The study navigates and sheds light on the interaction between influencers, who serve as marketers for these fast fashion products on social media, and their followers as recipients of the advertising and potential consumers. The interaction between both influencers and followers is explored through qualitative semi-structured interviews. The complex issue of fast fashion consumption is analyzed through a theoretical framework integrating Two-step flow theory, Cultivation theory, Social learning theory and the theory of Cognitive dissonance, as well as the respondents' attitudes, opinions, and positions. The purpose of the study is to illuminate the influential role of influencer marketing on followers' consumption and perception of fast fashion, particularly regarding the environmental aspects and sustainability. 

    The research questions are: "How do influencers shape followers' perspectives and purchasing behavior regarding fast fashion?", "How do followers reflect on their own fast fashion consumption affected by influencers on social media?", and "What other factors, besides influencers, can influence followers' consumption decisions regarding fast fashion?". In this qualitative study, the analysis of interviews with influencers and their followers reveals complex narratives and patterns in the context of fast fashion. Six key themes emerge, including; environmental awareness, ambivalence, the impact and power of influencers', responsibility, social norms and consumption culture. The analysis highlights followers' increased environmental awareness and their simultaneous struggle with impulsive consumption. Influencers play a central role in shaping followers' views and behaviors and acting as trendsetters. However, followers express concerns about collective and environmental responsibility, portraying influencers as having a dominant position when regarding fashion consumption through social media. 

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  • Berglund, Karl
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Literature and Rhetoric, Sociology of Literature.
    Gulddal, Jesper
    School of Humanities, Creative Industries and Social Sciences, University of Newcastle, Callaghan, Australia.
    King, Stewart
    School of Languages, Literatures, Cultures and Linguistics, Monash University, Clayton, Australia.
    On top of the world: Mapping the Nordic crime fiction boom based on translation data2024In: Translation Studies, ISSN 1478-1700, E-ISSN 1751-2921Article in journal (Refereed)
    Abstract [en]

    Nordic Noir – crime fiction originating in the Nordic region – is one of the most significant international publishing success stories of the twenty-first century. Despite its importance, no one has mapped and analysed the circulation of Nordic Noir as world literature. The present study addresses this knowledge gap by quantitatively mapping the global translation flows of Nordic Noir during the period of its greatest international success, from 2000 to 2020. Drawing on the “Nordic Noir in Translation Database” containing 8,886 translations from all five main Nordic languages – Danish, Finnish, Icelandic, Norwegian and Swedish – this study is the first to chart the so-called “boom” in a comparative macro perspective, bringing to light the nuances of its international dissemination and impact. Key findings relate to the chronological structure of the boom, the scale of Swedish dominance and the role of a small group of top authors in driving overall translation rates.

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  • Gallego, Ana
    et al.
    Univ Jyvaskyla, Fac Educ & Psychol, Dept Psychol, Jyvaskyla, Finland.;Univ Jyvaskyla, Sch Wellbeing, JYUWell, Jyvaskyla, Finland..
    Serrat, Mayte
    Vall Hebron Hosp, Unitat Expertesa Sindromes Sensibilitzacio Cent, Serv Reumatol, Barcelona, Spain..
    Royuela-Colomer, Estibaliz
    Autonomous Univ Barcelona, Fac Psychol, Dept Clin & Hlth Psychol, Bellaterra, Spain..
    Sanabria-Mazo, Juan P.
    Parc Sanit St Joan Deu, Sant Boi De Llobregat, Spain.;Autonomous Univ Barcelona, Dept Basic Dev & Educ Psychol, Fac Psychol, Barcelona, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Borras, Xavier
    Autonomous Univ Barcelona, Dept Basic Dev & Educ Psychol, Fac Psychol, Barcelona, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Esteve, Montserrat
    Univ Barcelona, Dept Biochem & Mol Biomed, Barcelona, Spain.;Univ Barcelona, Inst Biomed IBUB, Barcelona, Spain.;CIBER Physiopathol Obes & Nutr CIBEROBN, Madrid, Spain..
    Grasa, Mar
    Univ Barcelona, Dept Biochem & Mol Biomed, Barcelona, Spain.;Univ Barcelona, Inst Biomed IBUB, Barcelona, Spain.;CIBER Physiopathol Obes & Nutr CIBEROBN, Madrid, Spain..
    Rosa, Araceli
    Dept Evolut Biol, Unit Zool & Biol Anthropol, Ecol & Environm Sci, Barcelona, Spain.;CIBER Mental Hlth CIBERSAM, Madrid, Spain. Care Policy & Evaluat Ctr CPEC, London Sch Econ & Polit Sci, Dept HealthPolicy, London, England..
    Rozadilla-Sacanell, Antoni
    Parc Sanit St Joan Deu, Sant Boi De Llobregat, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Almirall, Miriam
    Vall Hebron Hosp, Unitat Expertesa Sindromes Sensibilitzacio Cent, Serv Reumatol, Barcelona, Spain..
    D'Amico, Francesco
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;London Sch Econ & Polit Sci, Dept Hlth Policy, Hlth Policy & Econ, London, England..
    Dai, Yifei
    Swing Therapeut Inc, San Francisco, CA 94111 USA..
    Rosenbluth, Michael J.
    Swing Therapeut Inc, San Francisco, CA 94111 USA..
    McCracken, Lance
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Navarrete, Jaime
    Parc Sanit St Joan Deu, Sant Boi De Llobregat, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Feliu-Soler, Albert
    Autonomous Univ Barcelona, Fac Psychol, Dept Clin & Hlth Psychol, Bellaterra, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Luciano, Juan, V
    Autonomous Univ Barcelona, Fac Psychol, Dept Clin & Hlth Psychol, Bellaterra, Spain.;Parc Sanit St Joan Deu, Sant Boi De Llobregat, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Study protocol for a three-arm randomized controlled trial investigating the effectiveness, cost-utility, and physiological effects of a fully self-guided digital Acceptance and Commitment Therapy for Spanish patients with fibromyalgia2024In: Digital Health, E-ISSN 2055-2076, Vol. 10, article id 20552076241239177Article in journal (Refereed)
    Abstract [en]

    Objective: Fibromyalgia (FM) is a prevalent pain syndrome with significant healthcare and societal costs. The aim of the SMART-FM-SP study is to determine the effectiveness, cost-utility, and physiological effects in patients with FM of a digital intervention (STANZA (R)) currently marketed in the United States, which delivers smartphone-based, fully self-guided Acceptance and Commitment Therapy (Digital ACT) for treating FM-related symptoms.

    Methods: A single-site, parallel-group, superiority, randomized controlled trial (RCT) will be conducted, including a total of 360 adults diagnosed with FM. Individuals will be randomly allocated (1:1:1) to treatment as usual (TAU), to TAU plus 12 weeks of treatment with Digital ACT, or to TAU plus 12 weeks of treatment with digital symptom tracking (i.e. FibroST). Participants will be assessed at baseline, post-treatment, and 6-month follow-up. An intention-to-treat analysis using linear mixed models will be computed to analyze the effects of Digital ACT on functional impairment (primary outcome), as measured by the Fibromyalgia Impact Questionnaire Revised at 6 months from the inception of the treatment. Secondary outcomes include impression of change, symptoms of distress, pain catastrophising, quality of life, cost-utility, and selected biomarkers (cortisol and cortisone, immune-inflammatory markers, and FKBP5 gene polymorphisms). The role of ACT-related processes of change will be tested with path analyses.

    Conclusions: This study is the first RCT that tests Digital ACT for Spanish patients with FM. Results will be important not only for patients and clinicians, but also for policy makers by examining the cost-utility of the app in a public healthcare context.

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  • Kirk, Ben
    et al.
    Univ Melbourne, Melbourne Med Sch, Dept Med, Western Hlth, Melbourne, Vic, Australia.;Univ Melbourne, Australian Inst Musculoskeletal Sci AIMSS, Melbourne, Vic, Australia.;Western Hlth, Melbourne, Vic, Australia..
    Cawthon, Peggy M.
    Calif Pacific Med Ctr, Res Inst, 550 16th St,Second Floor, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA..
    Arai, Hidenori
    Natl Ctr Geriatr & Gerontol, Obu, Aichi, Japan..
    Avila-Funes, Jose A.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Geriatr, Mexico City, Mexico.;Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, UMR 1219, Inserm, F-33000 Bordeaux, France..
    Barazzoni, Rocco
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Bhasin, Shalender
    Harvard Med Sch, Brigham & Womens Hosp, Boston Claude D Pepper Older Amer Independence Ct, Boston, MA USA..
    Binder, Ellen F.
    Washington Univ, Sch Med, Div Gen Med & Geriatr, St Louis, MO USA..
    Bruyere, Olivier
    Univ Liege, WHO Collaborating Ctr Publ Hlth Aspects Musculo S, Div Publ Hlth Epidemiol & Hlth Econ, Liege, Belgium.;Univ Liege, Dept Sport & Rehabil Sci, Liege, Belgium..
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Karolinska Univ Hosp, Theme Inflammat & Ageing, Stockholm, Sweden..
    Chen, Liang-Kung
    Taipei Vet Gen Hosp, Ctr Geriatr & Gerontol, Taipei, Taiwan.;Natl Yang Ming Chiao Tung Univ, Ctr Hlth Longev & Aging Sci, Taipei, Taiwan..
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, England.;Univ Oxford, Dept Epidemiol, Oxford, England..
    Duque, Gustavo
    McGill Univ, Bone Muscle & Gerosci Grp, Res Inst, Hlth Ctr, Montreal, PQ, Canada.;McGill Univ, Dr Joseph Kaufmann Chair Geriatr Med, Dept Med, Montreal, PQ, Canada..
    Fielding, Roger A.
    Tufts Univ, Jean Mayer US Dept Agr, Nutr Exercise Physiol & Sarcopenia Lab, Human Nutr Res Ctr Aging, Boston, MA USA..
    Guralnik, Jack
    Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD USA..
    Kiel, Douglas P.
    Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA.;Harvard Med Sch, Hinda & Arthur Marcus Inst Aging Res, Hebrew SeniorLife, Boston, MA USA..
    Landi, Francesco
    Fdn Policlin Univ Agostino Gemelli IRCCS, I-00168 Rome, Italy..
    Reginster, Jean-Yves
    WHO Collaborating Ctr Epidemiol Musculoskeletal H, Liege, Belgium.;King Saud Univ, Coll Sci, Chair Biomarkers Chron Dis, Riyadh, Saudi Arabia..
    Sayer, Avan A.
    Newcastle Univ, Newcastle Hosp, AGE Res Grp, NIHR Newcastle Biomed Res Ctr, Newcastle, England.;Newcastle Univ, Fac Med Sci, Newcastle, England..
    Visser, Marjolein
    Vrije Univ Amsterdam, Fac Sci, Dept Hlth Sci, Amsterdam, Netherlands.;Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands..
    von Haehling, Stephan
    Univ Med Gottingen UMG, Dept Cardiol & Pneumol, Gottingen, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Gottingen, Gottingen, Germany..
    Woo, Jean
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Cruz-Jentoft, Alfonso J.
    Hosp Univ Ramon y Cajal IRYCIS, Serv Geriatria, Madrid, Spain..
    The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS)2024In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 53, no 3, article id afae052Article in journal (Refereed)
    Abstract [en]

    Importance Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. Objective The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. Design The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. Results 107 participants (mean age: 54 +/- 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. Conclusion and relevance The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

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  • Greco, Raffaella
    et al.
    Univ Vita Salute San Raffaele, IRCCS San Raffaele Hosp, Unit Hematol & Bone Marrow Transplantat, Milan, Italy.;Practice Harmonizat & Guidelines Comm EBMT, Barcelona, Spain.;ADWP EBMT, Barcelona, Spain.;Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Hematol & Bone Marrow Transplantat Unit, Via Olgettina 60, I-20132 Milan, Italy..
    Alexander, Tobias
    Charite Univ Med Berlin, Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.;Berlin Inst Hlth, Dept Rheumatol & Clin Immunol, Berlin, Germany..
    Del Papa, Nicoletta
    Univ Milan, Rheumatol Dept, Scleroderma Clin, ASST G Pini CTO, Milan, Italy..
    Mueller, Fabian
    Univ Hosp Erlangen, Dept Internal Med Hematol & Oncol 5, Erlangen, Germany.;Bayr Zentrum Krebsforsch BZKF, Erlangen, Germany..
    Saccardi, Riccardo
    Careggi Univ Hosp, Cellular Therapies & Transfus Med Unit, Florence, Italy..
    Sanchez-Guijo, Fermin
    Univ Salamanca, IBSAL Univ Hosp Salamanca, Dept Hematol, Salamanca, Spain.;Univ Salamanca, Dept Med, Salamanca, Spain..
    Schett, Georg
    FAU Erlangen Nurnberg, Dept Internal Med Rheumatol & Immunol 3, Erlangen, Germany.;Univ Klinikum Erlangen, Erlangen, Germany.;Friedrich Alexander Univ FAU Erlangen Nurnberg, Deutsch Zentrum Immuntherapie, Univ Klinikum Erlangen, Erlangen, Germany..
    Sharrack, Basil
    Sheffield Teaching Hosp NHS Fdn Trust, Dept Neurosci & Sheffield NIHR Translat Neurosci B, Sheffield, England.;Univ Sheffield, Sheffield, England..
    Snowden, John A.
    Univ Sheffield, Sheffield Teaching Hosp NHS Fdn Trust, Sch Med & Populat Hlth, Dept Haematol,Div Clin Med, Sheffield, England..
    Tarte, Karin
    Univ Rennes, SITI Lab, CHU Rennes, EFS Bretagne, Rennes, France..
    Onida, Francesco
    Univ Milan, Hematol & ASCT Unit, ASST Fatebenefratelli Sacco, Milan, Italy.;Practice Harmonizat & Guidelines Comm EBMT, Barcelona, Spain..
    Sanchez-Ortega, Isabel
    Secretary Practice Harmonizat & Guidelines Comm EB, Barcelona, Spain.;Execut Off, Barcelona, Spain..
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Llorente, Cristina Castilla
    Gustave Roussy, Hematol Dept, Villejuif, France..
    Cervera, Ricard
    Hosp Clin Barcelona, Reference Ctr Syst Autoimmune Dis UEC CSUR, Dept Autoimmune Dis, Catalan & Spanish Hlth Syst ERN ReCONNET, ,Catalonia, Barcelona, Catalonia, Spain..
    Ciceri, Fabio
    Univ Vita Salute San Raffaele, IRCCS San Raffaele Hosp, Unit Hematol & Bone Marrow Transplantat, Milan, Italy..
    Doria, Andrea
    Univ Padua, Dept Med DiMED, Rheumatol Unit, Padua, Italy..
    Henes, Joerg
    Univ Hosp Tuebingen, Ctr Interdisciplinary Rheumatol Immunol & Autoimmu, Tubingen, Germany.;Univ Hosp Tuebingen, Dept Internal Med Haematol Oncol Clin Immunol & Rh, Tubingen, Germany..
    Lindsay, James
    Royal London Hosp, Dept Gastroenterol, Barts Hlth NHS Trust, London, England.;Queen Mary Univ London, Blizard Inst, Ctr Immunobiol, Barts & London Sch Med & Dent, London, England..
    Mackensen, Andreas
    Univ Hosp Erlangen, Dept Internal Med Hematol & Oncol 5, Erlangen, Germany..
    Muraro, Paolo A.
    Imperial Coll London, Dept Brain Sci, London, England..
    Ricart, Elena
    Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Gastroenterol Dept, Barcelona, Spain..
    Rovira, Montserrat
    Univ Barcelona, Hosp Clin, Inst Haematol & Oncol, Haematol Dept,BMT Unit,IDIBAPS, Barcelona, Spain.;Josep Carreras Leukaemia Res Fdn, Barcelona, Spain..
    Zuckerman, Tsila
    Technion, Rambam Hlth Care Campus & Rappaport Fac Med, Haifa, Israel..
    Yakoub-Agha, Ibrahim
    Univ Lille, CHU Lille, INSERM, U1286,Infinite, F-59000 Lille, France.;Practice Harmonizat & Guidelines Comm EBMT, Barcelona, Spain..
    Farge, Dominique
    Paris Cite Univ, St Louis Hosp, Ctr Reference Malad Autoimmunes Syst Rares Ile De, Internal Med Unit 04,CRMR MATHEC,AP HP,Malad Autoi, Paris, France.;McGill Univ, Dept Med, Montreal, PQ, Canada.;St Louis Hosp, AP HP, Malad Autoimmunes & Therapie Cellulaire, Internal Med Unit UF CRMR MATHEC 04, 1 Ave Claude Vellefaux, F-75010 Paris, France..
    Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee2024In: eClinicalMedicine, E-ISSN 2589-5370, Vol. 69, article id 102476Article in journal (Refereed)
    Abstract [en]

    Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert -based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • Malmgren, Johan
    et al.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Anaesthesiol & Intens Care Med,Inst Clin Sci, Bla Straket 5, S-41345 Gothenburg, Sweden..
    Lundin, Stefan
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Anaesthesiol & Intens Care Med,Inst Clin Sci, Bla Straket 5, S-41345 Gothenburg, Sweden..
    Waldenström, Ann-Charlotte
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Oncol,Inst Clin Sci, S-41345 Gothenburg, Sweden..
    Rylander, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Johannesson, Elias
    Univ West, Dept Social & Behav Studies, Trollhättan, Sweden..
    Quality of life-related and non-quality of life-related issues in ICU survivors and non-ICU-treated controls: a multi-group exploratory factor analysis2024In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 28, no 1, article id 102Article in journal (Refereed)
    Abstract [en]

    Background

    Quality of life (QoL) is a key outcome measure in healthcare. However, the heterogeneity in its definitions presents challenges in the objective evaluation of improvement. Universal questionnaires, tailored for a broad demographic group, inadequately represent the unique experiences of intensive care unit (ICU) survivors, including a lack of ability to discriminate issues related to QoL from issues that do not.

    Methods

    Using a 218-item, 13-domain provisional questionnaire, we assessed 395 adult ICU survivors, with a minimum 72-h stay at one of three Swedish university hospital ICUs, at 6 months to three years post-discharge. Their responses were compared to those of 195 controls, matched for age and sex and randomly recruited from the Swedish Population Registry. By multi-group exploratory factor analysis, we compared dimensionality in QoL perceptions between the two groups, emphasising patterns of correlation to 13 domain-specific QoL questions. Model fit was assessed using information criteria. Internal consistency reliability for each scale was determined using McDonald’s omega or Cronbach’s alpha. All analyses were conducted using Mplus, applying full information maximum likelihood to handle missing data.

    Results

    All domains except Cognition had a subset of questions correlating to the domain-specific QoL question in at least the ICU survivor group. The similarity between the two groups varied, with Physical health, Sexual health and Gastrointestinal (GI) functions mainly correlating the same issues to QoL in the two groups. In contrast, Fatigue, Pain, Mental health, activities of daily living, Sleep, Sensory functions and Work life showed considerable differences. In all, about one-fourth of the issues correlated to QoL in the ICU survivor group and about one-tenth of the issues in the control group.

    Conclusions

    We found most issues experienced by ICU survivors to be unrelated to quality of life. Our findings indicate that the consequences of post-ICU issues may play a more significant role in affecting QoL than the issues themselves; issues restricting and affecting social life and work life were more related to QoL in ICU survivors than in non-ICU-treated controls. Caution is advised before associating all post-ICU problems with an effect on quality of life.

    Trial registration: ClinicalTrials.gov Ref# NCT02767180; Registered 28 April 2016.

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  • Dastanpour, Esmat
    et al.
    KTH Royal Inst Technol, Dept Mat Sci & Engn, SE-10044 Stockholm, Sweden..
    Huang, Shuo
    China Univ Geosci, Fac Mat Sci & Chem, Wuhan 430074, Peoples R China..
    Ström, Valter
    KTH Royal Inst Technol, Dept Mat Sci & Engn, SE-10044 Stockholm, Sweden..
    Varga, Lajos Karoly
    Wigner Res Ctr Phys, Inst Solid State Phys & Opt, H-1525 Budapest, Hungary..
    Vitos, Levente
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Dept Mat Sci & Engn, SE-10044 Stockholm, Sweden..
    Schönecker, Stephan
    KTH Royal Inst Technol, Dept Mat Sci & Engn, SE-10044 Stockholm, Sweden..
    An assessment of the Al50Cr21-xMn17+xCo12 (x=0, 4, 8) high-entropy alloys for magnetocaloric refrigeration application2024In: Journal of Alloys and Compounds, ISSN 0925-8388, E-ISSN 1873-4669, Vol. 984, article id 173977Article in journal (Refereed)
    Abstract [en]

    This study investigates the magnetocaloric potential of the Al50Cr21-xMn17+xCo12 (x=0, 4, 8 at%) high-entropy alloy (HEA) series using integrated experimental and theoretical approaches. Structural analysis by X-ray diffraction and scanning electron microscopy indicate a dual phase containing B2 and body-centered cubic (BCC) structures. Magnetic characterization shows an approximately linear decrease in saturation magnetization and Curie temperature with increasing Cr content. Curie temperatures calculated by Monte Carlo simulations suggest that the measured magnetic properties originate from the B2 phase rather than the BCC phase. The enhanced magnetocaloric effect with decreasing Cr content highlights the attractiveness of HEAs in magnetocaloric applications.

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  • Virtanen, Anton
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Implementeringen av Nord2000 i svenska bullerutredningar: En jämförelse mellan de Nordiska beräkningsmetoderna och Nord20002024Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Noise caused by road and rail traffic is an environmental issue that is receiving increasing attention. It has long been known that prolonged exposure to noise can lead to a range of health problems, but in recent years, it has also been shown to have a negative impact on biodiversity. In Sweden, the Nordic calculation methods (Nord96) are currently used to assess noise levels generated by road and rail traffic. However, there is a consensus among acousticians that this method is outdated. In Sweden, it has been decided to transition to the more modern Nord2000 method in 2024. Therefore, it is essential to compare the Nordic calculation method with Nord2000 to determine any potential consequences. The responsibility for this transition has been assigned to Kunskapcentrum om buller which has developed a user manual aimed at ensuring that the calculation comparisons provide results as accurately comparable as possible.

    The aim of this thesis was to identify any shortcomings from an implementation perspective in the developed user manual and to compare the two calculation methods, Nord96 and Nord2000, for road and rail traffic. Twelve scenarios were constructed in the noise modeling program SoundPLAN 9.0 to study potential differences. Furthermore, calculations were made for a real case in an area in Farsta, Stockholm.

    Findings showed differences in the calculated sound levels between the two calculation methods for road and rail traffic. The results suggest that a transition may lead to it being more challenging to meet guideline values at outdoor areas in shielded locations for road traffic and at facades facing the noise source for rail traffic. Furthermore, several points of improvement regarding the developed user manual were identified. It was concluded that values for input parameters such as road surface temperature and traffic flow distribution should be clarified, and more information on the selection of weather parameters is needed.

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  • Mackaay, Marco
    et al.
    Inst Super Tecn, Ctr Math Anal Geometry & Dynam Syst, Dept Matemat, P-1049001 Lisbon, Portugal.;Univ Algarve, Dept Matemat, FCT, Campus Gambelas, P-8005139 Faro, Portugal..
    Mazorchuk, Volodymyr
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Algebra, Logic and Representation Theory.
    Miemietz, Vanessa
    Univ East Anglia, Sch Math, Norwich NR4 7TJ, England..
    Kostant's problem for fully commutative permutations2024In: Revista matemática iberoamericana, ISSN 0213-2230, E-ISSN 2235-0616, Vol. 40, no 2, p. 537-563Article in journal (Refereed)
    Abstract [en]

    We give a complete combinatorial answer to Kostant's problem for simple highest weight modules indexed by fully commutative permutations. We also propose a reformulation of Kostant's problem in the context of fiab bicategories and classify annihilators of simple objects in the principal birepresentations of such bicategories generalizing the Barbasch-Vogan theorem for Lie algebras.

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  • Bergfeldt, Nora
    et al.
    Stockholm Univ, Ctr Palaeogenet, Stockholm, Sweden.;Stockholm Univ, Dept Zool, Stockholm, Sweden.;Swedish Museum Nat Hist, Dept Bioinformat & Genet, Stockholm, Sweden..
    Kirdök, Emrah
    Mersin Univ, Inst Sci, Dept Biotechnol, Mersin, Turkiye..
    Oskolkov, Nikolay
    Lund Univ, Dept Biol, Sci Life Lab, Natl Bioinformat Infrastructure Sweden, Lund, Sweden..
    Mirabello, Claudio
    Linköping Univ, Dept Phys Chem & Biol, Sci Life Lab, Linköping, Sweden..
    Unneberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Malmström, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Human Evolution.
    Fraser, Magdalena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Human Evolution.
    Sanchez-Quinto, Federico
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Human Evolution.
    Jorgensen, Roger
    Univ Tromso, Arctic Univ Norway, Tromso Univ Museum, Tromso, Norway..
    Skar, Birgitte
    NTNU Univ Museum, Dept Archaeol & Cultural Hist, Trondheim, Norway..
    Liden, Kerstin
    Stockholm Univ, Dept Archaeol & Class Studies, Stockholm, Sweden..
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Human Evolution.
    Storå, Jan
    Stockholm Univ, Dept Archaeol & Class Studies, Stockholm, Sweden..
    Götherström, Anders
    Stockholm Univ, Ctr Palaeogenet, Stockholm, Sweden.;Stockholm Univ, Dept Archaeol & Class Studies, Stockholm, Sweden..
    Identification of microbial pathogens in Neolithic Scandinavian humans2024In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 5630Article in journal (Refereed)
    Abstract [en]

    With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts.

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    FULLTEXT01
  • Abbasi, R.
    et al.
    Loyola Univ Chicago, Dept Phys, Chicago, IL 60660 USA.
    Beise, Jakob
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Botner, Olga
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Coleman, Alan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Glaser, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Glüsenkamp, Thorsten
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics. Friedrich Alexander Univ Erlangen Nurnberg, Erlangen Ctr Astroparticle Phys, D-91058 Erlangen, Germany..
    Hallgren, Allan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Heyer, Nils
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    O'Sullivan, Erin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Pérez de los Heros, Carlos
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Pontén, Axel
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Valtonen-Mattila, Nora
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zimmerman, M.
    Univ Wisconsin Madison, Dept Phys, Madison, WI 53706 USA;Univ Wisconsin Madison, Wisconsin IceCube Particle Astrophys, Madison, WI 53706 USA.
    Search for Continuous and Transient Neutrino Emission Associated with IceCube's Highest-energy Tracks: An 11 yr Analysis2024In: Astrophysical Journal, ISSN 0004-637X, E-ISSN 1538-4357, Vol. 964, no 1, article id 40Article in journal (Refereed)
    Abstract [en]

    IceCube alert events are neutrinos with a moderate-to-high probability of having astrophysical origin. In this study, we analyze 11 yr of IceCube data and investigate 122 alert events and a selection of high-energy tracks detected between 2009 and the end of 2021. This high-energy event selection (alert events + high-energy tracks) has an average probability of >= 0.5 of being of astrophysical origin. We search for additional continuous and transient neutrino emission within the high-energy events' error regions. We find no evidence for significant continuous neutrino emission from any of the alert event directions. The only locally significant neutrino emission is the transient emission associated with the blazar TXS 0506+056, with a local significance of 3 sigma, which confirms previous IceCube studies. When correcting for 122 test positions, the global p-value is 0.156 and compatible with the background hypothesis. We constrain the total continuous flux emitted from all 122 test positions at 100 TeV to be below 1.2 x 10-15 (TeV cm2 s)-1 at 90% confidence assuming an E -2 spectrum. This corresponds to 4.5% of IceCube's astrophysical diffuse flux. Overall, we find no indication that alert events in general are linked to lower-energetic continuous or transient neutrino emission.

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  • Lannebo, Elsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Government.
    Redo för demokrati: Att utveckla demokratiska värderingar och förmågor2024Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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  • Gustafsson, Oscar
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Peace and Conflict Research.
    Medias syn på krigsoffer: Det ideala offret2024Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Denna studie har undersökt medias beskrivning av offren i konflikten mellan Israel och Hamas/Palestina och hur beskrivningen skiljer sig åt. Det teoretiska ramverkat utgörs av en ideologisk aspekt där imperialismen ligger till grund för ett ställningstagande inom en vänsterorienterad respektive högerorienterad syn på konflikten. Utgångspunkten för analysen har varit att undersöka medias beskrivningar av offren genom en socialkonstruktivistisk hållning där Nils Christies teori om det ideala brottsoffret varit i fokus. En textanalys av olika artiklar från Aftonbladet och Svenska Dagbladet har studerats och analyserats utifrån studiens teoretiska hållning. Resultatet från den insamlade empirin visar att det finns en skillnad i hur offren framställs i artiklarna utifrån de två olika tidningarna i studien.

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    Kandidatuppsats freds- och konfliktstudier
  • Jacobsson, Tilda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Peace and Conflict Research.
    Left outside or left unattended?: A qualitative case study on the effect of outside spoiling on post-war criminal violence2024Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Some peace processes are tainted by more violence than the actual conflict, sometimes worsened by spoilers. Although spoilers pose a threat to the writing or lasting of peace agreements, they do not always succeed, and instead, peace can flourish. Despite this, the effects of spoiling violence on society have not been thoroughly explored. Research suggests that criminal violence thrives in the post-war period, this paper aims to answer the research question: How do spoilers affect post-war criminal violence? As spoilers instil insecurity, the hypothesis is that post-war criminal violence will increase within a state if the peace agreements have experienced outside spoiling. To investigate this, a Structured Focused Comparison approach is employed, comparing two cases, El Salvador and Sierra Leone. However, this paper was unable to find support for the proposed causal relationship between outside spoiling and post-war criminal violence. Further research is needed to understand how spoilers affect both the peace process and criminal violence.

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  • Wetter, Elsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Peace and Conflict Research.
    Legitimacy during rebel rule: A qualitative study on how rebel governance affect domestic legitimacy2024Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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  • Public defence: 2024-05-03 09:00 Ekmansalen, 15:00024, EBC, Uppsala
    Cediel-Ulloa, Andrea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Physiology and Environmental Toxicology.
    Novel Endpoints To Unravel Developmental Neurotoxicity: From DNA methylation responses to methylmercury to the in vitro identification of endocrine disruptors2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The developing brain is especially sensitive to environmental stressors due to its dependence on the precise spatiotemporal regulation of multiple signals, and the long time period required for its formation. Some chemicals can interfere with molecular and cellular processes driving brain development, including epigenetic processes such as DNA methylation. Hence, identification of DNA methylation changes induced by chemical exposure may serve as early molecular markers for developmental neurotoxicity (DNT). Chemicals known as endocrine disruptors (EDCs) can produce adverse effects due to their capability to alter the endocrine system. Since brain development is highly dependent on endocrine signals, the potential adverse effects of EDCs on brain development needs to be addressed. Detection of DNT in the regulatory context has been based on in vivo testing, however, the financial costs and time intensive characteristics of these methods have resulted in a limited assessment of the DNT hazard of chemicals. In addition, in order to regulate EDCs, it is paramount to demonstrate that their adverse effects are a product of disruption of endocrine signals. Yet, at the moment, there are no approved methods which address both an endocrine mode of action and adverse neurodevelopmental outcomes. This doctoral thesis had two main aims: Firstly, to identify epigenetic changes, at the level of DNA methylation, underlying DNT induced by exposure to methylmercury (MeHg); and secondly, to develop new approach methods (NAMs) for the detection of DNT induced by endocrine disruption. Epigenetic effects were studied both in epidemiological data and experimentally in vitro. Associations between prenatal MeHg exposure and DNA methylation of GRIN2B and NR3C1 were found in children. In vitro validation of DNA methylation changes found in epigenome-wide association studies of populations exposed to MeHg, uncovered the potential involvement of the Mediator Complex Subunit 31 (MED31) in MeHg DNT. To contribute to the endocrine disruption (ED)-induced DNT field, the applicability of an in vitro model composed of murine neural progenitor cells (the C17.2 cell-line) was evaluated. We found that C17.2 neural differentiation and morphology were sensitive to retinoic acid (RAR), retinoic X (RXR), peroxisome proliferator-activated β/δ (PPARβ/δ), and glucocorticoid (GR) agonism. Furthermore, two out of 25 tested EDCs decreased neurite outgrowth and branching in the C17.2 system. These effects were recovered by co-exposure of the chemicals with antagonists of RAR, RXR, or PPARβ/δ, indicating that their DNT effect is mediated by hormonal disruption. Altogether, this thesis contributed to the development of new methodologies and endpoints for the assessment of DNT induced by MeHg and EDCs.  

    List of papers
    1. Prenatal methylmercury exposure and DNA methylation in seven-year-old children in the Seychelles Child Development Study
    Open this publication in new window or tab >>Prenatal methylmercury exposure and DNA methylation in seven-year-old children in the Seychelles Child Development Study
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    2021 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 147, article id 106321Article in journal (Refereed) Published
    Abstract [en]

    Background

    Methylmercury (MeHg) is present in fish and is a neurotoxicant at sufficiently high levels. One potential mechanism of MeHg toxicity early in life is epigenetic dysregulation that may affect long-term neurodevelopment. Altered DNA methylation of nervous system-related genes has been associated with adult mental health outcomes.

    Objective

    To assess associations between prenatal MeHg exposure and DNA methylation (at the cytosine of CG dinucleotides, CpGs) in three nervous system-related genes, encoding brain-derived neurotropic factor (BDNF), glutamate receptor subunit NR2B (GRIN2B), and the glucocorticoid receptor (NR3C1), in children who were exposed to MeHg in utero.

    Methods

    We tested 406 seven-year-old Seychellois children participating in the Seychelles Child Development Study (Nutrition Cohort 2), who were prenatally exposed to MeHg from maternal fish consumption. Total mercury in maternal hair (prenatal MeHg exposure measure) collected during pregnancy was measured using atomic absorption spectroscopy. Methylation in DNA from the children’s saliva was measured by pyrosequencing. To assess associations between prenatal MeHg exposure and CpG methylation at seven years of age, we used multivariable linear regression models adjusted for covariates.

    Results

    We identified associations with prenatal MeHg exposure for DNA methylation of one GRIN2B CpG and two NR3C1 CpGs out of 12 total CpG sites. Higher prenatal MeHg was associated with higher methylation for each CpG site. For example, NR3C1 CpG3 had an expected increase of 0.03-fold for each additional 1 ppm of prenatal MeHg (B = 0.030, 95% CI 0.001, 0.059; p = 0.047). Several CpG sites associated with MeHg are located in transcription factor binding sites and the observed methylation changes are predicted to lead to lower gene expression.

    Conclusions

    In a population of people who consume large amounts of fish, we showed that higher prenatal MeHg exposure was associated with differential DNA methylation at seven years of age at specific CpG sites that may influence neurodevelopment and mental health.

    Place, publisher, year, edition, pages
    Elsevier, 2021
    Keywords
    Methylmercury, MeHg, Epigenetic, DNA methylation, Neurodevelopment, Fish consumption, Early life
    National Category
    Medical Genetics Occupational Health and Environmental Health
    Identifiers
    urn:nbn:se:uu:diva-435974 (URN)10.1016/j.envint.2020.106321 (DOI)000613512700006 ()33340986 (PubMedID)
    Funder
    Swedish Research Council FormasNIH (National Institute of Health), R01-ES010219NIH (National Institute of Health), P30-ES01247
    Available from: 2021-06-30 Created: 2021-06-30 Last updated: 2024-03-14Bibliographically approved
    2. Methylmercury-induced DNA methylation-From epidemiological observations to experimental evidence
    Open this publication in new window or tab >>Methylmercury-induced DNA methylation-From epidemiological observations to experimental evidence
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    2022 (English)In: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 13, article id 993387Article in journal (Refereed) Published
    Abstract [en]

    Methylmercury (MeHg) is a developmental neurotoxicant, and one potential mechanism of MeHg toxicity is epigenetic dysregulation. In a recent meta-analysis of epigenome-wide association studies (EWAS), associations between prenatal MeHg exposure and DNA methylation at several genomic sites were identified in blood from newborns and children. While EWASs reveal human-relevant associations, experimental studies are required to validate the relationship between exposure and DNA methylation changes, and to assess if such changes have implications for gene expression. Herein, we studied DNA methylation and gene expression of five of the top genes identified in the EWAS meta-analysis, MED31, MRPL19, GGH, GRK1, and LYSMD3, upon MeHg exposure in human SH-SY5Y cells exposed to 8 or 40 nM of MeHg during differentiation, using bisulfite-pyrosequencing and qPCR, respectively. The concentrations were selected to cover the range of MeHg concentrations in cord blood (2-8.5 mu g/L) observed in the cohorts included in the EWAS. Exposure to MeHg increased DNA methylation at MED31, a transcriptional regulator essential for fetal development. The results were in concordance with the epidemiological findings where more MED31 methylation was associated with higher concentrations of MeHg. Additionally, we found a non-significant decrease in DNA methylation at GGH, which corresponds to the direction of change observed in the EWAS, and a significant correlation of GGH methylation with its expression. In conclusion, this study corroborates some of the EWAS findings and puts forward candidate genes involved in MeHg's effects on the developing brain, thus highlighting the value of experimental validation of epidemiological association studies.

    Place, publisher, year, edition, pages
    Frontiers Media S.A., 2022
    Keywords
    methyl mercury (MeHg), neurodevelopment, epigenome wide association study, DNA methylation, SH-SY5Y cell line
    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:uu:diva-486701 (URN)10.3389/fgene.2022.993387 (DOI)000861603100001 ()36176303 (PubMedID)
    Funder
    Swedish Research Council, 2016-02387Swedish Fund for Research Without Animal Experiments, F2019-0009Swedish Fund for Research Without Animal Experiments, F2020-0006EU, Horizon 2020, 825759
    Available from: 2022-10-14 Created: 2022-10-14 Last updated: 2024-03-14Bibliographically approved
    3. The C17.2 cell line as testing system for endocrine disruption-induced developmental neurotoxicity
    Open this publication in new window or tab >>The C17.2 cell line as testing system for endocrine disruption-induced developmental neurotoxicity
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Hormone signaling plays an essential role during fetal life and is vital for brain development. Endocrine-disrupting chemicals (EDCs) can interfere with the hormonal milieu in this critical time period, disrupting key neurodevelopmental processes. Hence, there is a need for the development of assays that evaluate developmental neurotoxicity (DNT) induced by an endocrine mode of action. Herein, we evaluated the applicability of the neural progenitor C17. 2 cell-line, as an in vitro test method to aid in the detection of endocrine disruption induced DNT. For this, C17.2 cells were exposed during 10 days of differentiation to (ant)agonists of the thyroid hormone (Thr), glucocorticoid (Gr), retinoic acid (Rar), retinoic x (Rxr), oxysterols (Lxr), estrogen (Er), androgen (Ar), and peroxisome proliferator activated delta (Ppard) receptors, as well as to the agonist of the vitamin D (Vdr) receptor. Upon exposure and differentiation, the cells were incubated with Hoechst (nuclear staining) and subsequently stained for βIII-tubulin (neuronal marker) by immunofluorescence. Automated imaging was carried out with a 10X objective lens using an ImageXpress micro xls system (Molecular Devices) and image analysis was performed with MetaXpress® software (Molecular Devices). The C17.2 cells were responsive to the Rar and Rxr agonists which decreased neurite outgrowth, branching and neuronal differentiation as well as to the Rar antagonist which increased neurite outgrowth and branching. With this approach, we have identified that the C17.2 cells are responsive to Gr, Rar, Rxr, and Pparβ/δ, hence contributing to the development of reliable and transferable test methods for hazard assessment of EDCs.

    Keywords
    Endocrine disruptors, neurodevelopment, in vitro assay development, retinoic acid, Peroxisome proliferator-activated receptor
    National Category
    Biochemistry and Molecular Biology Cell and Molecular Biology
    Research subject
    Biology with specialization in Environmental Toxicology
    Identifiers
    urn:nbn:se:uu:diva-524945 (URN)
    Funder
    EU, Horizon 2020, 825759
    Available from: 2024-03-14 Created: 2024-03-14 Last updated: 2024-03-14Bibliographically approved
    4. The pesticides endosulfan and cypermethrin affect neuronal differentiation via retinoic and peroxisome proliferator receptor activity
    Open this publication in new window or tab >>The pesticides endosulfan and cypermethrin affect neuronal differentiation via retinoic and peroxisome proliferator receptor activity
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Brain development is highly dependent on hormonal homeostasis, hence developmental exposure to endocrine disrupting chemicals (EDCs) is of high concern. In fact, epidemiological and in vivo studies support associations between exposure to EDCs and impaired neurodevelopment. However, the existing hazard assessment of EDCs does not consider developmental neurotoxicity (DNT) prompting an urgent requirement for innovative testing and screening tools addressing endocrine disruption (ED)-induced DNT. We have previously shown the applicability of the immortalized murine neural progenitor cells, C17.2 cells, for addressing ED-DNT. We evidenced decreased neurite outgrowth and branching when the cells were exposed to the Rar, Rxr or Pparβ/δ agonists, and concluded that this is a suitable model for the evaluation of ED-induced DNT for chemicals disrupting Rar, Rxr or Pparβ/δ signalling. In this study we further validated the C17.2 method by testing the effects of 25 EDCs on the same neuronal morphology endpoints as reported in the previous paper. Out of the tested chemicals, endosulfan and cypermethrin decreased, while benzyl butyl phthalate (BBzP) increased neurite outgrowth and branching. We proceeded to evaluate whether these effects were mediated by Rar, Rxr or Ppar β/δ agonism. The neuronal morphology effects of endosulfan and cypermethrin were rescued by co-exposures Rar and Rxr antagonists, and partially rescued by the Ppar β/δ antagonist indicating a common mechanism. With this approach, we have identified that the C17.2 cells can be used as an in vitro model to address ED-induced DNT.

    Keywords
    Endocrine disruptors, Developmental neurotoxicity, Retinoids, Peroxisome proliferator-activated receptor, in vitro testing
    National Category
    Biochemistry and Molecular Biology
    Research subject
    Biology; Biology with specialization in Environmental Toxicology
    Identifiers
    urn:nbn:se:uu:diva-524946 (URN)
    Available from: 2024-03-14 Created: 2024-03-14 Last updated: 2024-03-14Bibliographically approved
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  • Public defence: 2024-05-07 13:15 A1:111a, Uppsala
    Tofiq, Maryam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Tableting performance of dry granulated particles: Significance and assessment of compression mechanical properties2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dry granulation (DG) is often utilized as an intermediate process during tablet manufacturing, for improving flow characteristics of the powder blend and/or reducing segregation issues related to the active pharmaceutical ingredient (API). The resulting granules exhibit typically irregular shapes with rough surfaces and their mechanical properties are related to the feeding powder and the process parameters used during the DG. Most frequently, a reduced tabletability of the dry granulated particles is reported compared to the feed powder, referred as loss of tabletability (LoT). A sufficient mechanical strength of the tablet is required to survive further handling, processing and packing. In this thesis the LoT has been addressed by structure-property-performance interrelationships. To achieve this, dry granulated particles were prepared with controlled physical properties, utilizing systematically variated starting powders of a typical brittle (crystalline α-lactose monohydrate) and a typical plastic material (microcrystalline cellulose). Consequently, the granule mechanical properties ranged from an extensive brittle character to a plastic character. In addition, analytical powder compression was employed to understand the overall compression mechanisms of dry granulated particles during tableting and to determine descriptors (parameters) that reflects the granule mechanical property which controls the LoT. 

    The compression mechanisms of dry granulated particles were found to occur in a series of phases in sequence. In the first phase, at very low compression pressure, rearrangement of the granules occurred until a jamming point was reached. The second phase was dominated by granule fragmentation which occurred at relatively low pressure with a high compression rate. The third phase was dominated by plastic deformation and occurred at high pressure with a decreased compression rate. Finally, the compression mechanisms ceased at the highest tableting pressure (300 MPa) which involved an elastic deformation of the formed tablet. Among the compression parameters studied, the Adams parameters were found to be the most valuable descriptors of granule fragmentation and deformation. Thus, it was concluded that both granule fragmentation and deformation affect the LoT depending on the tablet pressure. At low tablet pressure (up to 100 MPa) the degree of granule fragmentation was found to be the critical mechanism controlling LoT, which depended on the brittleness of the granules. Conversely, at higher pressure (above 100 MPa) the degree of granule deformation was the critical mechanism controlling LoT, which depended on the plasticity of the granules. In conclusion, the LoT was dependent on granule structure and granule mechanical property. 

    List of papers
    1. Effect of excipient properties and blend ratio on the compression properties of dry granulated particles prepared from microcrystalline cellulose and lactose
    Open this publication in new window or tab >>Effect of excipient properties and blend ratio on the compression properties of dry granulated particles prepared from microcrystalline cellulose and lactose
    2022 (English)In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 399, article id 117207Article in journal (Refereed) Published
    Abstract [en]

    In this study, the effect of a systematically varied excipient ratio of a plastic and a brittle material, i.e., microcrystalline cellulose (MCC) and crystalline a-lactose monohydrate (LAC), on the compression properties of dry granulated particles was investigated. Five powders with different MCC:LAC ratios were prepared by dry mixing; subsequently, they were formed into slugs that were milled and sieved, giving granules of two size fractions. Two slugging pressures were used, giving granules of different porosity for each powder. Original powders and granules were compressed, and strain-pressure profiles determined. From these profiles, a series of compression parameters were derived using the Heckel, Kawakita, and Adams compression equations. The initial part of the compression profiles of all granulated powders were similar up to a jamming point, after which the compression profiles diverged depending on the granule composition and the slugging pressure. Parameters derived from the Adams and Kawakita equations reflected the differences in compression behavior, while the Heckel parameter did not. The macroscopic compression stiffening was assessed by the Adams friction parameter which seemed to be controlled by the inner friction of the granules, i.e., their plastic deformation due to inter-particulate flow. The total compressibility, assessed by the Kawakita parameter, was dependent on the initial bulk porosity of the granulations. It is concluded that the composition, microstructure, and packing density of the granules dictated their compression properties, while the granule size and work hardening of primary particles were insignificant.

    Place, publisher, year, edition, pages
    ElsevierElsevier BV, 2022
    Keywords
    Dry granulation, Granule composition, Granule strength, Powder compression, Compression parameters, Granule deformation
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:uu:diva-474328 (URN)10.1016/j.powtec.2022.117207 (DOI)000788074900008 ()
    Funder
    Vinnova, Dnr 2017-02690Vinnova, Dnr 2019-00048
    Available from: 2022-05-18 Created: 2022-05-18 Last updated: 2024-03-12Bibliographically approved
    2. Deciphering the role of granule deformation and fragmentation for the tableting performance of some dry granulated powders
    Open this publication in new window or tab >>Deciphering the role of granule deformation and fragmentation for the tableting performance of some dry granulated powders
    2022 (English)In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 409, article id 117794Article in journal (Refereed) Published
    Abstract [en]

    In this study, the question of how fragmentation and deformation of granules during compression can be linked to the tableting performance of dry granulated powders is addressed. Granulated powders of a systematically varied composition of a plastic and a brittle material were prepared by slugging and thereafter compacted into tablets. The tablet's micro-structure, porosity, and tensile strength were assessed; moreover, the relationships between the Adams compression parameters tau(0) and alpha and the tableting performance were studied. The composition and the slugging pressure had a limited effect on the tablet porosity. However, they had a marked effect on the tablet micro-structure, which varied from tablets composed of deformed but otherwise preserved granules to tablets composed of small granule fragments. The tablet tensile strength, the loss of tab-letability, and the lubricant sensitivity varied with the Adams compression parameters, indicating a complex effect of granule fragmentation and deformation on the tableting performance. The effect of the granule compression properties on the tableting performance is mediated by the number and average force of the intergranular bonds of the tablet.

    Place, publisher, year, edition, pages
    ElsevierElsevier BV, 2022
    Keywords
    Granule composition, Dry granulation, Adams compression parameters, Tablet tensile strength, Loss of tabletability, Lubricant sensitivity
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:uu:diva-483758 (URN)10.1016/j.powtec.2022.117794 (DOI)000843005800004 ()
    Funder
    Vinnova, Dnr 2017-02690Vinnova, Dnr 2019-00048Swedish Research Council, 2019-00207
    Available from: 2022-09-02 Created: 2022-09-02 Last updated: 2024-03-12Bibliographically approved
    3. The interplay between compression mechanisms and compaction pressure in relation to the loss of tabletability of dry granulated particles
    Open this publication in new window or tab >>The interplay between compression mechanisms and compaction pressure in relation to the loss of tabletability of dry granulated particles
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:uu:diva-524585 (URN)
    Available from: 2024-03-07 Created: 2024-03-07 Last updated: 2024-03-12
    4. Relationships between mechanical properties, compression properties, and tabletability of dry granulated particles of different composition
    Open this publication in new window or tab >>Relationships between mechanical properties, compression properties, and tabletability of dry granulated particles of different composition
    (English)Manuscript (preprint) (Other academic)
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:uu:diva-524586 (URN)
    Available from: 2024-03-07 Created: 2024-03-07 Last updated: 2024-03-12
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    UUThesis_M-Tofiq-2024
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  • Dubois, Kévin
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    On compound coastal flooding2024Licentiate thesis, comprehensive summary (Other academic)
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  • Public defence: 2024-05-07 09:15 Rudbecksalen, Uppsala
    Nyström, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Inflammation, Metabolism and Child Health Research. Uppsala University Children's Hospital, Gastroenterology and nutrition.
    Metabolomic features and viral infections in paediatric inflammatory bowel disease2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Up to 25% of patients with inflammatory bowel disease have a paediatric onset (PIBD). The pathophysiological processes underlying PIBD are complex and largely unknown.  

    Aims: To investigate a hypothesized role for human enterovirus B (HEV-B) in Crohn’s disease (CD) (I). To map and compare the mucosal and plasma metabolomes in new-onset PIBD patients and controls (II). To search for a new blood-based diagnostic biomarker for PIBD (III). To investigate the effect of exclusive enteral nutrition (EEN) treatment on the mucosal and plasma metabolomes in CD patients (IV). 

    Methods: Immunohistochemistry and chromogen in situ hybridisation were used to search for HEV-B in surgical specimens from patients who had undergone surgery for stricturing ileocecal CD, and from volvulus patients as controls. Ultra-high-performance liquid chromatography mass spectrometry were used on biopsies and plasma from patients in the Uppsala PIBD inception cohort for metabolomic (II and IV) and lipidomic analyses (III). Patients were stratified by phenotypic subtypes and treatment responses. Symptomatic patients without PIBD were used as non-IBD controls. In Study III, two other independent PIBD inception cohorts were used for validation and confirmation. 

    Results: I: HEV-B was detected in epithelial cells and neuronal ganglia of the enteric nervous system, and the specific cellular Coxsackie and adenovirus receptor (CAR) was expressed in both the intestinal epithelium and the enteric nervous system. II: Alterations in two metabolic compound classes were seen: decreased levels of lysophospholipids in inflamed ileum of CD patients and altered levels of sphingolipids in inflamed ileum and colon in both CD and ulcerative colitis, as compared with non-IBD controls. III: Discovery, validation and confirmation in three independent PIBD inception cohorts of a blood-based diagnostic two-lipid signature of PIBD. IV: A generalised downregulation of the non-inflamed ileal lipid metabolism after successful remission induction with EEN, as compared with baseline, and also as compared with non-IBD controls. Reduction of several lysophospholipids was a characteristic feature of the post-EEN ileal metabolome.

    Conclusions: The demonstrated presence of HEV-B supports, but does not confirm, its hypothesised role in CD. The CD-associated downregulation of mucosal metabolism both at disease onset and after successful EEN-induced inflammation resolution indicates a central role for the ileal mucosal lipid metabolism in CD, including lysophospholipids. The blood-based two-lipid signature has the potential of becoming a diagnostic tool in the clinical work-up of suspected PIBD.

    List of papers
    1. Human enterovirus species B in ileocecal Crohn's disease
    Open this publication in new window or tab >>Human enterovirus species B in ileocecal Crohn's disease
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    2013 (English)In: Clinical and Translational Gastroenterology, E-ISSN 2155-384X, Vol. 4, article id e38Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES:

    Advanced ileocecal Crohn's disease (ICD) is characterized by strictures, inflammation in the enteric nervous system (myenteric plexitis), and a high frequency of NOD2 mutations. Recent findings implicate a role of NOD2 and another CD susceptibility gene, ATG16L1, in the host response against single-stranded RNA (ssRNA) viruses. However, the role of viruses in CD is unknown. We hypothesized that human enterovirus species B (HEV-B), which are ssRNA viruses with dual tropism both for the intestinal epithelium and the nervous system, could play a role in ICD.

    METHODS:

    We used immunohistochemistry and in situ hybridization to study the general presence of HEV-B and the presence of the two HEV-B subspecies, Coxsackie B virus (CBV) and Echovirus, in ileocecal resections from 9 children with advanced, stricturing ICD and 6 patients with volvulus, and in intestinal biopsies from 15 CD patients at the time of diagnosis.

    RESULTS:

    All patients with ICD had disease-associated polymorphisms in NOD2 or ATG16L1. Positive staining for HEV-B was detected both in the mucosa and in myenteric nerve ganglia in all ICD patients, but in none of the volvulus patients. Expression of the cellular receptor for CBV, CAR, was detected in nerve cell ganglia.

    CONCLUSIONS:

    The common presence of HEV-B in the mucosa and enteric nervous system of ICD patients in this small cohort is a novel finding that warrants further investigation to analyze whether HEV-B has a role in disease onset or progress. The presence of CAR in myenteric nerve cell ganglia provides a possible route of entry for CBV into the enteric nervous system.

    National Category
    Basic Medicine Gastroenterology and Hepatology
    Research subject
    Pathology
    Identifiers
    urn:nbn:se:uu:diva-224046 (URN)10.1038/ctg.2013.7 (DOI)23804031 (PubMedID)
    Funder
    Swedish Research CouncilSwedish Cancer SocietySwedish Childhood Cancer Foundation
    Note

    De två sista författarna delar sistaförfattarskapet.

    Available from: 2014-04-30 Created: 2014-04-30 Last updated: 2024-03-20Bibliographically approved
    2. Mucosal and Plasma Metabolomes in New-onset Paediatric Inflammatory Bowel Disease: Correlations with Disease Characteristics and Plasma Inflammation Protein Markers
    Open this publication in new window or tab >>Mucosal and Plasma Metabolomes in New-onset Paediatric Inflammatory Bowel Disease: Correlations with Disease Characteristics and Plasma Inflammation Protein Markers
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    2023 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no 3, p. 418-432Article in journal (Refereed) Published
    Abstract [en]

    Background and Aims

    To advance the understanding of inflammatory bowel disease [IBD] pathophysiology, we compared the mucosal and plasma metabolomes between new-onset paediatric IBD patients and symptomatic non-IBD controls, and correlated plasma inflammation markers and disease characteristics with the altered metabolites.

    Methods

    Paired colonic and ileal biopsies and plasma from 67 treatment-naïve children with incident Crohn’s disease [CD; n = 47], ulcerative colitis [UC; n = 9], and non-IBD controls [n = 11] were analysed using ultra-performance liquid chromatography-mass spectrometry [UPLC-MS/MS]. Inflammatory plasma proteins [n = 92] were assessed.

    Results

    The metabolomes in inflamed mucosal biopsies differed between IBD patients and controls. In CD, mucosal levels of several lysophospholipids [lysophosphatidylcholines, lysophosphatidyletanolamines, lysophosphatidylinositols, and lysophosphatidylserines] were decreased, correlating with various plasma metabolites including amino acid analogues and N-acetylated compounds. In both CD and UC, mucosal sphingolipids, including ceramide [d18:2/24:1, d18:1/24:2], lactosyl-N-palmitoyl-sphingosine [d18:1/16:0], behenoyl sphingomyelin [d18:1/22:0], lignoceroyl sphingomyelin [d18:1/24:0], and/or sphingomyelin [d18:1/24:1, d18:2/24:0] were increased, correlating with sphingolipids, bile acids, and/or N-acetylated metabolites in plasma. Among proteins associated with CD, interleukin-24 correlated with plasma metabolites, including lactosyl-N-palmitoyl sphingosine [d18:1/16:0] and phosphatidyletanolamine [18:1/18:1], haemoglobin, and faecal calprotectin. In UC, interleukin-24, interleukin-17A, and C-C motif chemokine 11 correlated with several plasma metabolites, including N-acetyltryptophan, tryptophan, glycerate, and threonate, and with the Paediatric Ulcerative Colitis Activity Index, C-reactive protein, and faecal calprotectin.

    Conclusions

    Mucosal perturbations of lysophospholipids and sphingolipids characterised the metabolome in new-onset paediatric IBD and correlated with plasma metabolites. By integrating plasma metabolomics data with inflammatory proteins and clinical data, we identified clinical and inflammatory markers associated with metabolomic signatures for IBD.

    Place, publisher, year, edition, pages
    Oxford University Press, 2023
    Keywords
    Inflammatory bowel disease, metabolome, paediatric
    National Category
    Gastroenterology and Hepatology Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-524107 (URN)10.1093/ecco-jcc/jjac149 (DOI)36219554 (PubMedID)
    Funder
    Swedish Foundation for Strategic Research, RB13-0160NordForsk, 90 569Vinnova, 2019-01185Swedish Research Council, 2020-02021Swedish Research Council, 2020-04707Gillbergska stiftelsen
    Available from: 2024-02-28 Created: 2024-02-28 Last updated: 2024-03-20Bibliographically approved
    3. Identification and validation of a blood-based diagnostic lipidomic signature of paediatric inflammatory bowel disease
    Open this publication in new window or tab >>Identification and validation of a blood-based diagnostic lipidomic signature of paediatric inflammatory bowel disease
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    2024 (English)Manuscript (preprint) (Other academic)
    Keywords
    Inflammatory Bowel Disease, Ulcerative colitis, Crohn's disease, pediatric, lipidomics, metabolomics, biomarkers
    National Category
    Gastroenterology and Hepatology
    Research subject
    Pediatrics; Pediatrics; Pediatrics; Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-524423 (URN)
    Available from: 2024-03-18 Created: 2024-03-18 Last updated: 2024-03-20
    4. Mucosal and plasma responses reflect the outcome of exclusive enteral nutrition treatment in new-onset paediatric Crohn's disease
    Open this publication in new window or tab >>Mucosal and plasma responses reflect the outcome of exclusive enteral nutrition treatment in new-onset paediatric Crohn's disease
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    (English)Manuscript (preprint) (Other academic)
    Keywords
    Inflammatory bowel disease, Crohn's disease, EEN, exclusive enteral nutrition, lipidomics, metabolomics
    National Category
    Gastroenterology and Hepatology
    Research subject
    Pediatrics; Internal Medicine
    Identifiers
    urn:nbn:se:uu:diva-525198 (URN)
    Available from: 2024-03-18 Created: 2024-03-18 Last updated: 2024-03-20
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    UUThesis_N-Nyström-2024
  • Nechaeva, T.
    et al.
    Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany..
    Verra, L.
    CERN, CH-1211 Geneva 23, Switzerland..
    Pucek, J.
    Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany..
    Ranc, L.
    Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany..
    Bergamaschi, M.
    Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany..
    Della Porta, G. Zevi
    Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany.;CERN, CH-1211 Geneva 23, Switzerland..
    Muggli, P.
    Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany..
    Agnello, R.
    Ecole Polytech Fed Lausanne EPFL, Swiss Plasma Ctr SPC, CH-1015 Lausanne, Switzerland..
    Ahdida, C. C.
    CERN, CH-1211 Geneva 23, Switzerland..
    Amoedo, C.
    CERN, CH-1211 Geneva 23, Switzerland..
    Andrebe, Y.
    Ecole Polytech Fed Lausanne EPFL, Swiss Plasma Ctr SPC, CH-1015 Lausanne, Switzerland..
    Apsimon, O.
    Univ Manchester, Manchester M13 9PL, England.;Cockcroft Inst, Warrington WA4 4AD, England..
    Apsimon, R.
    Cockcroft Inst, Warrington WA4 4AD, England.;Univ Lancaster, Lancaster LA1 4YB, England..
    Arnesano, J. M.
    CERN, CH-1211 Geneva 23, Switzerland..
    Bencini, V.
    CERN, CH-1211 Geneva 23, Switzerland.;Univ Oxford, John Adams Inst, Oxford OX1 3RH, England..
    Blanchard, P.
    Ecole Polytech Fed Lausanne EPFL, Swiss Plasma Ctr SPC, CH-1015 Lausanne, Switzerland..
    Burrows, P. N.
    Univ Oxford, John Adams Inst, Oxford OX1 3RH, England..
    Buttenschoen, B.
    Max Planck Inst Plasma Phys, D-17491 Greifswald, Germany..
    Caldwell, A.
    Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany..
    Chung, M.
    UNIST, Dept Phys, Ulsan 44919, South Korea..
    Cooke, D. A.
    UCL, London WC1 6BT, England..
    Davut, C.
    Univ Manchester, Manchester M13 9PL, England..
    Demeter, G.
    Wigner Res Ctr Phys, H-1121 Budapest, Hungary..
    Dexter, A. C.
    Cockcroft Inst, Warrington WA4 4AD, England.;Univ Lancaster, Lancaster LA1 4YB, England..
    Doebert, S.
    CERN, CH-1211 Geneva 23, Switzerland..
    Farmer, J.
    Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany..
    Fasoli, A.
    Ecole Polytech Fed Lausanne EPFL, Swiss Plasma Ctr SPC, CH-1015 Lausanne, Switzerland..
    Fonseca, R.
    ISCTE Inst Universiteario Lisboa, P-1049001 Lisbon, Portugal.;GoLP Inst Plasmas & Fusao Nucl, Inst Super Tecn, Univ Lisboa, P-1049001 Lisbon, Portugal..
    Furno, I.
    Ecole Polytech Fed Lausanne EPFL, Swiss Plasma Ctr SPC, CH-1015 Lausanne, Switzerland..
    Granados, E.
    CERN, CH-1211 Geneva 23, Switzerland..
    Granetzny, M.
    Univ Wisconsin, Madison, WI 53706 USA..
    Graubner, T.
    Philipps Univ Marburg, D-35032 Marburg, Germany..
    Grulke, O.
    Tech Univ Denmark, DK-2800 Lyngby, Denmark..
    Gschwendtner, E.
    CERN, CH-1211 Geneva 23, Switzerland..
    Guran, E.
    CERN, CH-1211 Geneva 23, Switzerland..
    Henderson, J.
    Cockcroft Inst, Warrington WA4 4AD, England.;Daresbury Lab, STFC ASTeC, Warrington WA4 4AD, England..
    Kedves, M. A.
    Wigner Res Ctr Phys, H-1121 Budapest, Hungary..
    Kim, S. -Y
    Kraus, F.
    Philipps Univ Marburg, D-35032 Marburg, Germany..
    Krupa, M.
    CERN, CH-1211 Geneva 23, Switzerland..
    Lefevre, T.
    CERN, CH-1211 Geneva 23, Switzerland..
    Liang, L.
    Univ Manchester, Manchester M13 9PL, England.;Cockcroft Inst, Warrington WA4 4AD, England..
    Liu, S.
    TRIUMF, Vancouver, BC V6T 2A3, Canada..
    Lopes, N.
    GoLP Inst Plasmas & Fusao Nucl, Inst Super Tecn, Univ Lisboa, P-1049001 Lisbon, Portugal..
    Lotov, K.
    RAS, SB RAS, SB, Novosibirsk 630090, Russia.;Novosibirsk State Univ, Novosibirsk 630090, Russia..
    Calderon, M. Martinez
    CERN, CH-1211 Geneva 23, Switzerland..
    Mazzoni, S.
    CERN, CH-1211 Geneva 23, Switzerland..
    Moon, K.
    UNIST, Dept Phys, Ulsan 44919, South Korea..
    Guzman, P. I. Morales
    Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany..
    Moreira, M.
    GoLP Inst Plasmas & Fusao Nucl, Inst Super Tecn, Univ Lisboa, P-1049001 Lisbon, Portugal..
    Okhotnikov, N.
    RAS, SB RAS, SB, Novosibirsk 630090, Russia.;Novosibirsk State Univ, Novosibirsk 630090, Russia..
    Pakuza, C.
    Univ Oxford, John Adams Inst, Oxford OX1 3RH, England..
    Pannell, F.
    UCL, London WC1 6BT, England..
    Pardons, A.
    CERN, CH-1211 Geneva 23, Switzerland..
    Pepitone, Kevin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, FREIA.
    Poimenidou, E.
    CERN, CH-1211 Geneva 23, Switzerland..
    Pukhov, A.
    Heinrich Heine Univ Dusseldorf, D-40225 Dusseldorf, Germany..
    Rey, S.
    CERN, CH-1211 Geneva 23, Switzerland..
    Rossel, R.
    CERN, CH-1211 Geneva 23, Switzerland..
    Saberi, H.
    Univ Manchester, Manchester M13 9PL, England.;Cockcroft Inst, Warrington WA4 4AD, England..
    Schmitz, O.
    Univ Wisconsin, Madison, WI 53706 USA..
    Senes, E.
    CERN, CH-1211 Geneva 23, Switzerland..
    Silva, F.
    Univ Lisbon, INESC ID, Inst Super Tecn, P-1049001 Lisbon, Portugal..
    Silva, L.
    GoLP Inst Plasmas & Fusao Nucl, Inst Super Tecn, Univ Lisboa, P-1049001 Lisbon, Portugal..
    Spear, B.
    Univ Oxford, John Adams Inst, Oxford OX1 3RH, England..
    Stollberg, C.
    Ecole Polytech Fed Lausanne EPFL, Swiss Plasma Ctr SPC, CH-1015 Lausanne, Switzerland..
    Sublet, A.
    CERN, CH-1211 Geneva 23, Switzerland..
    Swain, C.
    Univ Liverpool, Liverpool L69 7ZE, England..
    Topaloudis, A.
    CERN, CH-1211 Geneva 23, Switzerland..
    Torrado, N.
    CERN, CH-1211 Geneva 23, Switzerland.;GoLP Inst Plasmas & Fusao Nucl, Inst Super Tecn, Univ Lisboa, P-1049001 Lisbon, Portugal..
    Turner, M.
    CERN, CH-1211 Geneva 23, Switzerland..
    Velotti, F.
    CERN, CH-1211 Geneva 23, Switzerland..
    Verzilov, V.
    TRIUMF, Vancouver, BC V6T 2A3, Canada..
    Vieira, J.
    GoLP Inst Plasmas & Fusao Nucl, Inst Super Tecn, Univ Lisboa, P-1049001 Lisbon, Portugal..
    Welsch, C.
    Cockcroft Inst, Warrington WA4 4AD, England.;Univ Liverpool, Liverpool L69 7ZE, England..
    Wendt, M.
    CERN, CH-1211 Geneva 23, Switzerland..
    Wing, M.
    UCL, London WC1 6BT, England..
    Wolfenden, J.
    Cockcroft Inst, Warrington WA4 4AD, England.;Univ Liverpool, Liverpool L69 7ZE, England..
    Woolley, B.
    CERN, CH-1211 Geneva 23, Switzerland..
    Xia, G.
    Univ Manchester, Manchester M13 9PL, England.;Cockcroft Inst, Warrington WA4 4AD, England..
    Yarygova, V.
    RAS, SB RAS, SB, Novosibirsk 630090, Russia.;Novosibirsk State Univ, Novosibirsk 630090, Russia..
    Zepp, M.
    Univ Wisconsin, Madison, WI 53706 USA..
    Hosing of a Long Relativistic Particle Bunch in Plasma2024In: Physical Review Letters, ISSN 0031-9007, E-ISSN 1079-7114, Vol. 132, no 7, article id 075001Article in journal (Refereed)
    Abstract [en]

    Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, selfmodulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma -based accelerators and represent the first characterization of hosing.

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    FULLTEXT01
  • Lööf, Villiam
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Mervärdesskatt på NFT:s och liknande virtuella tillgångar: Hinner mervärdesskattesystemet med i samhällsutvecklingen?2024Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    It is a truism that the legal system lags behind societal and technological developments. The common system of VAT is no exception. The objective of this thesis is to examine how the existing VAT rules applies to virtual assets, in particular NFTs and purchasable collectibles in computer games. The aim is to study how transactions with these assets are classified from a VAT perspective and to evaluate whether this classification is compatible with the VAT neutrality principle and the function of VAT as a general tax on final consumption. 

    One finding related to the classification part of this thesis is that these transactions, which often involve a token and an underlying asset, are treated as a composite supply of services and not a supply of goods for VAT purposes. This implies that the special scheme for second-hand goods cannot be applied. Other classification aspects to assess whether the supply falls within the scope of VAT and whether the supply is taxed or exempt, are also analyzed. There is no ground for NFTs or other virtual assets to be exempt generally. Though, certain types or functions for NFTs may be exempt as financial transactions. The evaluation concludes that the existing rules are partly adapted to handle transactions with these types of virtual assets conducted in a virtual environment. However, the existing rules could lead to an unmotivated double taxation, which may preclude the pursuit of economic activities.

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  • Dorri, Samira
    et al.
    Linköping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys Div, SE-58183 Linköping, Sweden..
    Ghafoor, Naureen
    Linköping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys Div, SE-58183 Linköping, Sweden..
    Palisaitis, Justinas
    Linköping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys Div, SE-58183 Linköping, Sweden..
    Stendahl, Sjoerd
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Devishvili, Anton
    Inst Laue Langevin ILL, 71 Ave Martyrs CS 20156, Grenoble, France..
    Vorobiev, Alexei
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics. Inst Laue Langevin ILL, 71 Ave Martyrs CS 20156, Grenoble, France..
    Eriksson, Fredrik
    Linköping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys Div, SE-58183 Linköping, Sweden..
    Persson, Per O. Å.
    Linköping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys Div, SE-58183 Linköping, Sweden..
    Birch, Jens
    Linköping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys Div, SE-58183 Linköping, Sweden..
    Enhanced quality of single crystal CrBx/TiBy diboride superlattices by controlling boron stoichiometry during sputter deposition2024In: Applied Surface Science, ISSN 0169-4332, E-ISSN 1873-5584, Vol. 655, article id 159606Article in journal (Refereed)
    Abstract [en]

    Single-crystal CrB2/TiB2 diboride superlattices with well-defined layers are promising candidates for neutron optics. However, excess B in sputter-deposited TiBy using a single TiB2 target deteriorates the structural quality of CrBx/TiBy (0001) superlattices. We study the influence of co-sputtering of TiB2 + Ti on the stoichiometry and crystalline quality of 300-nm-thick TiBy single layers and CrBx/TiBy (0001) superlattices on Al2O3(0001) substrates grown by DC magnetron sputter epitaxy at growth-temperatures TS ranging from 600 to 900 °C. By controlling the relative applied powers to the TiB2 and Ti magnetrons, y could be reduced from 3.3 to 0.9. TiB2.3 grown at 750 °C exhibited epitaxial domains about 10x larger than non-co-sputtered films. Close-to-stoichiometry CrB1.7/TiB2.3 superlattices with modulation periods Λ = 6 nm grown at 750 °C showed the highest single crystal quality and best layer definition. TiB2.3 layers display rough top interfaces indicating kinetically limited growth while CrB1.7 forms flat and abrupt top interfaces indicating epitaxial growth with high adatom mobility.

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    fulltext
  • Swain, Ranjula Bali
    et al.
    Södertörn Univ, Dept Econ, S-14189 Huddinge, Stockholm, Sweden.;Stockholm Sch Econ, Ctr Sustainabil Res SIR, Box 6501, SE-11383 Stockholm, Sweden..
    Lin, Xiang
    Södertörn Univ, Dept Econ, S-14189 Huddinge, Stockholm, Sweden..
    Yang-Wallentin, Fan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    COVID-19 pandemic waves: Identification and interpretation of global data2024In: Heliyon, E-ISSN 2405-8440, Vol. 10, no 3, article id e25090Article in journal (Refereed)
    Abstract [en]

    The mention of the COVID-19 waves is as prevalent as the pandemic itself. Identifying the beginning and end of the wave is critical to evaluating the impact of various COVID-19 variants and the different pharmaceutical and non -pharmaceutical (including economic, health and social, etc.) interventions. We demonstrate a scientifically robust method to identify COVID-19 waves and the breaking points at which they begin and end from January 2020 to June 2021. Employing the Break Least Square method, we determine the significance of COVID-19 waves for global-, regional-, and country -level data. The results show that the method works efficiently in detecting different breaking points. Identifying these breaking points is critical for evaluating the impact of the economic, health, social and other welfare interventions implemented during the pandemic crisis. Employing our method with high frequency data effectively determines the start and end points of the COVID-19 wave(s). Identifying waves at the country level is more relevant than at the global or regional levels. Our research results evidenced that the COVID-19 wave takes about 48 days on average to subside once it begins, irrespective of the circumstances.

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    fulltext
  • Petch, Jeremy
    et al.
    Hamilton Hlth Sci, Ctr Data Sci & Digital Hlth, Hamilton, ON, Canada.;Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Dept Med, Div Cardiol, Hamilton, ON, Canada.;Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada..
    Nelson, Walter
    Hamilton Hlth Sci, Ctr Data Sci & Digital Hlth, Hamilton, ON, Canada.;Univ Toronto, Dept Stat Sci, Toronto, ON, Canada..
    Wu, Mary
    Univ Toronto, Dept Comp Sci, Toronto, ON, Canada..
    Ghassemi, Marzyeh
    MIT, Dept Elect Engn & Comp Sci, Cambridge, MA USA.;MIT, Inst Med & Evaluat Sci, Cambridge, MA USA.;Vector Inst, Toronto, ON, Canada..
    Benz, Alexander
    Populat Hlth Res Inst, Hamilton, ON, Canada.;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Cardiol, Mainz, Germany..
    Fatemi, Mehdi
    Microsoft Res, Montreal, PQ, Canada..
    Di, Shuang
    Hamilton Hlth Sci, Ctr Data Sci & Digital Hlth, Hamilton, ON, Canada.;Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada..
    Carnicelli, Anthony
    Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Granger, Christopher
    Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Giugliano, Robert
    Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA USA..
    Hong, Hwanhee
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA..
    Patel, Manesh
    Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Eikelboom, John
    Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Dept Med, Div Hematol & Thromboembolism, Hamilton, ON, Canada..
    Connolly, Stuart J.
    Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Dept Med, Div Cardiol, Hamilton, ON, Canada..
    Optimizing warfarin dosing for patients with atrial fibrillation using machine learning2024In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, article id 4516Article in journal (Refereed)
    Abstract [en]

    While novel oral anticoagulants are increasingly used to reduce risk of stroke in patients with atrial fibrillation, vitamin K antagonists such as warfarin continue to be used extensively for stroke prevention across the world. While effective in reducing the risk of strokes, the complex pharmacodynamics of warfarin make it difficult to use clinically, with many patients experiencing under- and/or over- anticoagulation. In this study we employed a novel implementation of deep reinforcement learning to provide clinical decision support to optimize time in therapeutic International Normalized Ratio (INR) range. We used a novel semi-Markov decision process formulation of the Batch-Constrained deep Q-learning algorithm to develop a reinforcement learning model to dynamically recommend optimal warfarin dosing to achieve INR of 2.0-3.0 for patients with atrial fibrillation. The model was developed using data from 22,502 patients in the warfarin treated groups of the pivotal randomized clinical trials of edoxaban (ENGAGE AF-TIMI 48), apixaban (ARISTOTLE) and rivaroxaban (ROCKET AF). The model was externally validated on data from 5730 warfarin-treated patients in a fourth trial of dabigatran (RE-LY) using multilevel regression models to estimate the relationship between center-level algorithm consistent dosing, time in therapeutic INR range (TTR), and a composite clinical outcome of stroke, systemic embolism or major hemorrhage. External validation showed a positive association between center-level algorithm-consistent dosing and TTR (R-2 = 0.56). Each 10% increase in algorithm-consistent dosing at the center level independently predicted a 6.78% improvement in TTR (95% CI 6.29, 7.28; p < 0.001) and a 11% decrease in the composite clinical outcome (HR 0.89; 95% CI 0.81, 1.00; p = 0.015). These results were comparable to those of a rules-based clinical algorithm used for benchmarking, for which each 10% increase in algorithm-consistent dosing independently predicted a 6.10% increase in TTR (95% CI 5.67, 6.54, p < 0.001) and a 10% decrease in the composite outcome (HR 0.90; 95% CI 0.83, 0.98, p = 0.018). Our findings suggest that a deep reinforcement learning algorithm can optimize time in therapeutic range for patients taking warfarin. A digital clinical decision support system to promote algorithm-consistent warfarin dosing could optimize time in therapeutic range and improve clinical outcomes in atrial fibrillation globally.

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  • Andersson, Claes
    et al.
    Malmö Univ, Dept Criminol, Malmö, Sweden.;Malmö Univ, Dept Criminol, S-20506 Malmö, Sweden..
    Berman, Anne H.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lindfors, Petra
    Stockholm Univ, Dept Psychol, Stockholm, Sweden..
    Bendtsen, Marcus
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Trust in academic management during the COVID-19 pandemic: longitudinal effects on mental health and academic self-efficacy2024In: Cogent Education, E-ISSN 2331-186X, Vol. 11, no 1, article id 2327779Article in journal (Refereed)
    Abstract [en]

    In higher education, students' trust in the university management may affect both mental health and academic self-efficacy. This longitudinal study, conducted during the most challenging course of the COVID-19 pandemic, uses multinomial regression and causal inference to estimate the effects of students' trust in their universities' strategies for managing the pandemic, on students' self-reported changes in mental health and academic self-efficacy. The analyzed sample (N = 2796) was recruited through online advertising and responded to a baseline online survey in the late spring of 2020, with two follow-up surveys five and ten months later. Results show that positive trust in university management of the pandemic protected against experiencing one's mental health and academic self-efficacy as worse rather than unchanged, both five and ten months after the baseline assessment. The findings emphasize the importance of developing and maintaining trust-building measures between academia and students to support students' mental health and academic self-efficacy in times of uncertainty.

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  • Mopoung, Kunpot
    et al.
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Ning, Weihua
    Soochow Univ, Inst Funct Nano & Soft Mat FUNSOM, Suzhou 215123, Peoples R China..
    Zhang, Muyi
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Ji, Fuxiang
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Mukhuti, Kingshuk
    Radboud Univ Nijmegen, High Field Magnet Lab HFML EMFL, NL-6525 ED Nijmegen, Netherlands..
    Engelkamp, Hans
    Radboud Univ Nijmegen, High Field Magnet Lab HFML EMFL, NL-6525 ED Nijmegen, Netherlands..
    Christianen, Peter C. M.
    Radboud Univ Nijmegen, High Field Magnet Lab HFML EMFL, NL-6525 ED Nijmegen, Netherlands..
    Singh, Utkarsh
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Klarbring, Johan
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Simak, Sergei I.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Abrikosov, Igor A.
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Gao, Feng
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Buyanova, Irina A.
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Chen, Weimin M.
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Puttisong, Yuttapoom
    Linköping Univ, Dept Phys IFM, S-58330 Linköping, Sweden..
    Understanding Antiferromagnetic Coupling in Lead-Free Halide Double Perovskite Semiconductors2024In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 128, no 12, p. 5313-5320Article in journal (Refereed)
    Abstract [en]

    Solution-processable semiconductors with antiferromagnetic (AFM) order are attractive for future spintronics and information storage technology. Halide perovskites containing magnetic ions have emerged as multifunctional materials, demonstrating a cross-link between structural, optical, electrical, and magnetic properties. However, stable optoelectronic halide perovskites that are antiferromagnetic remain sparse, and the critical design rules to optimize magnetic coupling still must be developed. Here, we combine the complementary magnetometry and electron-spin-resonance experiments, together with first-principles calculations to study the antiferromagnetic coupling in stable Cs2(Ag:Na)FeCl6 bulk semiconductor alloys grown by the hydrothermal method. We show the importance of nonmagnetic monovalence ions at the BI site (Na/Ag) in facilitating the superexchange interaction via orbital hybridization, offering the tunability of the Curie-Weiss parameters between -27 and -210 K, with a potential to promote magnetic frustration via alloying the nonmagnetic BI site (Ag:Na ratio). Combining our experimental evidence with first-principles calculations, we draw a cohesive picture of the material design for B-site-ordered antiferromagnetic halide double perovskites.

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  • Ablikim, M.
    et al.
    Inst High Energy Phys, Beijing 100049, Peoples R China.
    Adlarson, Patrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Johansson, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Kupsc, Andrzej
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics. Natl Ctr Nucl Res, PL-02093 Warsaw, Poland..
    Schönning, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Thoren, V.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Wolke, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Zu, J.
    State Key Lab Particle Detect & Elect, Beijing 100049, Peoples R China;Univ Sci & Technol China, Hefei 230026, Peoples R China.
    Measurements of Σ electromagnetic form factors in the timelike region using the untagged initial-state radiation technique2024In: Physical Review D: covering particles, fields, gravitation, and cosmology, ISSN 2470-0010, E-ISSN 2470-0029, Vol. 109, no 3, article id 034029Article in journal (Refereed)
    Abstract [en]

    The process e thorn e- -> sigma thorn sigma over bar - is studied from threshold up to 3.04 GeV=c2 via the initial -state radiation technique using data with an integrated luminosity of 12.0 fb-1, collected at center-of-mass energies between 3.773 and 4.258 GeV with the BESIII detector at the BEPCII collider. The pair production cross sections and the effective form factors of sigma are measured in eleven sigma thorn sigma over bar - invariant mass intervals from threshold to 3.04 GeV=c2. The results are consistent with the previous results from Belle and BESIII. Furthermore, the branching fractions of the decays J=psi ->sigma thorn sigma over bar - and psi o3686 thorn -> sigma thorn sigma over bar - are determined and the obtained results are consistent with the previous results of BESIII.

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  • Abbasi, Rasha
    et al.
    Loyola Univ Chicago, Dept Phys, Chicago, IL 60660 USA.
    Beise, Jakob
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Botner, Olga
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Glaser, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Hallgren, Allan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    O'Sullivan, Erin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Pérez de los Heros, Carlos
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Sharma, Ankur
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Valtonen-Mattila, Nora
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zhelnin, Pavel
    Harvard Univ, Dept Phys, Cambridge, MA 02138 USA;Harvard Univ, Lab Particle Phys & Cosmol, Cambridge, MA 02138 USA.
    In situ estimation of ice crystal properties at the South Pole using LED calibration data from the IceCube Neutrino Observatory2024In: The Cryosphere, ISSN 1994-0416, E-ISSN 1994-0424, Vol. 18, no 1, p. 75-102Article in journal (Refereed)
    Abstract [en]

    The IceCube Neutrino Observatory instruments about 1 km 3 of deep, glacial ice at the geographic South Pole. It uses 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. An unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. We examine birefringent light propagation through the polycrystalline ice microstructure as a possible explanation for this effect. The predictions of a first-principles model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties include not only the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube light-emitting diode (LED) calibration data, the theory and parameterization of the birefringence effect, the fitting procedures of these parameterizations to experimental data, and the inferred crystal properties.

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  • Koutsilieri, Stefania
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Mickols, Evgeniya
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Vegvari, Akos
    Karolinska Inst, Dept Med Biochem & Biophys, Div Chem 1, Stockholm, Sweden..
    Lauschke, Volker M.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.;Univ Tubingen, Tubingen, Germany..
    Proteomic workflows for deep phenotypic profiling of 3D organotypic liver models2024In: Biotechnology Journal, ISSN 1860-6768, E-ISSN 1860-7314, Vol. 19, no 3, article id e2300684Article in journal (Refereed)
    Abstract [en]

    Organotypic human tissue models constitute promising systems to facilitate drug discovery and development. They allow to maintain native cellular phenotypes and functions, which enables long-term pharmacokinetic and toxicity studies, as well as phenotypic screening. To trace relevant phenotypic changes back to specific targets or signaling pathways, comprehensive proteomic profiling is the gold-standard. A multitude of proteomic workflows have been applied on 3D tissue models to quantify their molecular phenotypes; however, their impact on analytical results and biological conclusions in this context has not been evaluated. The performance of twelve mass spectrometry-based global proteomic workflows that differed in the amount of cellular input, lysis protocols and quantification methods was compared for the analysis of primary human liver spheroids. Results differed majorly between protocols in the total number and subcellular compartment bias of identified proteins, which is particularly relevant for the reliable quantification of transporters and drug metabolizing enzymes. Using a model of metabolic dysfunction-associated steatotic liver disease, we furthermore show that critical disease pathways are robustly identified using a standardized high throughput-compatible workflow based on thermal lysis, even using only individual spheroids (1500 cells) as input. The results increase the applicability of proteomic profiling to phenotypic screens in organotypic microtissues and provide a scalable platform for deep phenotyping from limited biological material.

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  • Laurin, Emma
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Bengtsson, Felix
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of History of Science and Ideas.
    Genomströmning utan att tumma på kvalitén?: Studenters och utbildningsansvarigas erfarenheter av förskollärar- och grundlärarutbildningar vid Uppsala universitet2024Report (Other academic)
    Abstract [sv]

    I likhet med andra lärarutbildningar i Sverige och internationellt tampas förskollärar- och grundlärarutbildningarna vid Uppsala universitet med bristfällig genomströmning av studenter. Det vill säga att en relativt hög andel av de studenter som börjar på utbildningarna tar aldrig ut någon examen. För att få bättre kunskap om genomströmningen på förskollärar- och grundlärarutbildningarna vid Uppsala universitet gav fakultetsnämnden för utbildningsvetenskaper vid Uppsala universitet Centrum för högre utbildning och forskning som studieobjekt (HERO) i uppdrag att genomföra en kvantitativ och en kvalitativ studie. I denna rapport redogörs för den kvalitativa studien. 

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    Genomströmning utan att tumma på kvalitén?
  • Huuhtanen, Jani
    et al.
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;Aalto Univ, Dept Comp Sci, Espoo, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Adnan-Awad, Shady
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.;Fdn Finnish Canc Inst, Helsinki, Finland..
    Theodoropoulos, Jason
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Forsten, Sofia
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Warfvinge, Rebecca
    Lund Univ, Lund Stem Cell Ctr, Div Mol Hematol, Lund, Sweden..
    Dufva, Olli
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Bouhlal, Jonas
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Dhapola, Parashar
    Lund Univ, Lund Stem Cell Ctr, Div Mol Hematol, Lund, Sweden..
    Duan, Hanna
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Laajala, Essi
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Kasanen, Tiina
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Klievink, Jay
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Ilander, Mette
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland..
    Jaatinen, Taina
    Finnish Red Cross Blood Serv, Histocompatibil Testing Lab, Helsinki, Finland. Uppsala Univ, Dept Med Sci, Uppsala, Sweden. Uppsala Univ Hosp, Hematol Sect, Uppsala, Sweden..
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Finnish Red Cross Blood Serv, Histocompatibil Testing Lab, Helsinki, Finland. Uppsala Univ Hosp, Hematol Sect, Uppsala, Sweden..
    Hjorth-Hansen, Henrik
    St Olavs Hosp, Dept Hematol, Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Trondheim, Norway..
    Burchert, Andreas
    Philipps Univ Marburg, Dept Hematol Oncol & Immunol, Marburg, Germany.;Univ Med Ctr Giessen & Marburg, Marburg, Germany..
    Karlsson, Göran
    Fdn Finnish Canc Inst, Helsinki, Finland..
    Kreutzman, Anna
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland..
    Lähdesmäki, Harri
    Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland..
    Mustjoki, Satu
    Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland..
    Single-cell analysis of immune recognition in chronic myeloid leukemia patients following tyrosine kinase inhibitor discontinuation2024In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 38, p. 109-125Article in journal (Refereed)
    Abstract [en]

    Immunological control of residual leukemia cells is thought to occur in patients with chronic myeloid leukemia (CML) that maintain treatment-free remission (TFR) following tyrosine kinase inhibitor (TKI) discontinuation. To study this, we analyzed 55 single-cell RNA and T cell receptor (TCR) sequenced samples (scRNA+TCRαβ-seq) from patients with CML (n = 13, N = 25), other cancers (n = 28), and healthy (n = 7). The high number and active phenotype of natural killer (NK) cells in CML separated them from healthy and other cancers. Most NK cells in CML belonged to the active CD56dim cluster with high expression of GZMA/B, PRF1, CCL3/4, and IFNG, with interactions with leukemic cells via inhibitory LGALS9-TIM3 and PVR-TIGIT interactions. Accordingly, upregulation of LGALS9 was observed in CML target cells and TIM3 in NK cells when co-cultured together. Additionally, we created a classifier to identify TCRs targeting leukemia-associated antigen PR1 and quantified anti-PR1 T cells in 90 CML and 786 healthy TCRβ-sequenced samples. Anti-PR1 T cells were more prevalent in CML, enriched in bone marrow samples, and enriched in the mature, cytotoxic CD8+TEMRA cluster, especially in a patient maintaining TFR. Our results highlight the role of NK cells and anti-PR1 T cells in anti-leukemic immune responses in CML.

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  • Löfdahl Grelsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Civil and Industrial Engineering, Industrial Engineering and Management.
    Mekanism för återmontering av cykelkedja: Ett arbete om tillverkningsanpassning2023Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    There are many people in the world who use bikes in todays society. The problem with derailing of the drivechain has no standardized solution as of yet. This thesis is based on a prototype which would solve the problem for the cyclist without the need for stoping to remount the drivechain.The purpose of the thesis is to make new designs of the unique parts of the product and adapt them for suitable materials and manufacturing methods. Two manufacturing methods were also chosen in the thesis to calculate which of the methods were the most profitable at different sizes of the series. The last part was to remake the models of all parts so that they could be both easily applied and manufactured in a simple and profitable way. A simplified method of DFM (Design for Manufacturing) was used for the development of the product in writing this thesis along with consultations of professionals in their field.The result was not only a mechanism with better functionality but also a product adapted to two different manufacturing methods, machining and injection molding. The cost of the series studied in this thesis was large and big series are required for profitable manufacturing.

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  • Kishita, Naoko
    et al.
    Univ East Anglia, Sch Hlth Sci, Norwich, England..
    Czyznikowska, Barbara
    Univ Leicester, Ctr Ethn Hlth Res, Leicester, England..
    Riggey, Megan
    Univ East Anglia, Sch Hlth Sci, Norwich, England..
    Van Hout, Elien
    Univ East Anglia, Sch Hlth Sci, Norwich, England..
    Richmond, Erica
    Norfolk & Suffolk NHS Fdn Trust, Older Peoples Community Team, Norwich, England..
    Gould, Rebecca L.
    UCL, Div Psychiat, London, England..
    McCracken, Lance
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Farquhar, Morag
    Univ East Anglia, Sch Hlth Sci, Norwich, England..
    Carers' and therapists' views of internet-delivered guided self-help acceptance and commitment therapy for family carers of people with dementia (iACT4CARERS): a qualitative study in the context of ethnic minority families2024In: The Cognitive Behaviour Therapist, E-ISSN 1754-470X, Vol. 17, article id e11Article in journal (Refereed)
    Abstract [en]

    This study aimed to explore the views of family carers of people living with dementia from ethnic minority groups and their therapists on internet-delivered, self-help acceptance and commitment therapy for family carers (iACT4CARERS), enhanced with additional therapist guidance. To achieve this, a qualitative approach with semi-structured interviews was employed with ethnic minority carers who completed Enhanced iACT4CARERS (n=9) and therapists who supported them throughout the programme (n=5). The interviews were audio-recorded, transcribed and analysed using framework analysis. Four over-arching themes were identified: (1) Value of the programme to ethnic minority carers, (2) Barriers for ethnic minority carers, (3) Sense of connectedness through written feedback, and (4) Sense of connectedness through one-to-one sessions. Theme 1 reflected that ethnic minority carers valued ACT techniques, highlighting their usefulness and simplicity, leading to perceived benefits. Theme 2 revealed the irrelevance of examples provided of carer experiences throughout the programme due to differences in family carers' experiences of providing care within ethnic minority communities. Theme 3 highlighted that carers' engagement with the programme was facilitated by feelings of validation and encouragement received from their therapist via weekly written feedback. Finally, Theme 4 highlighted that additional one-to-one support sessions allowed both carers and therapists to develop strong therapeutic relationships. This enhanced subsequent text-based online interactions, allowing carers to be more open and engaged. Also, therapists reported that a strong sense of connectedness helped them to tailor their feedback. Enhanced iACT4CARERS that uses carers' experiences more relevant to ethnic minority communities may be more acceptable.

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  • Ho, Vanessa C.
    et al.
    Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA..
    Berman, Anne H.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Andrade, Jackie
    Univ Plymouth, Sch Psychol, Plymouth, England..
    Kavanagh, David J.
    Queensland Univ Technol, Sch Psychol & Counselling, Brisbane, Qld, Australia..
    Branche, Stephane La
    Int Panel Behav Change, Grenoble, France..
    May, Jon
    Univ Plymouth, Sch Psychol, Plymouth, England..
    Philson, Conner S.
    Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA..
    Blumstein, Daniel T.
    Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA..
    Assessing immediate emotions in the theory of planned behavior can substantially contribute to increases in pro-environmental behavior2024In: FRONTIERS IN CLIMATE, ISSN 2624-9553, Vol. 6, article id 1344899Article in journal (Refereed)
    Abstract [en]

    The Theory of Planned Behavior (TPB) is a highly influential and powerful behavior change model that offers promising guidance on promoting urgently needed, pro-environmental action. Recent pro-environmental research has successfully augmented TPB using anticipated emotions-the emotions an individual consciously predicts they will experience in relation to possible outcomes of their decision. However, immediate emotions-the emotions an individual actually experiences during decision-making-have received far less attention. Given that immediate emotions are relevant to pro-environmental decision-making and can address the theoretical and empirical limitations of TPB, we contend that pro-environmental studies should explicitly examine immediate emotions within the TPB framework. This article aims to stimulate rigorous research that enhances pro-environmental communication and policymaking by providing integrative insights into immediate emotions along with recommendations for evaluating immediate emotions in a pro-environmental TPB context.

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  • Arnadottir, Solrun Dogg
    et al.
    Univ Akureyri, Sch Hlth Sci, Akureyri, Iceland.;Landspitali Univ Hosp, Vasc Surg Unit, Reykjavik, Iceland..
    Palsdottir, Gudbjorg
    Landspitali Univ Hosp, Wound Care Unit, Reykjavik, Iceland..
    Logason, Karl
    Landspitali Univ Hosp, Vasc Surg Unit, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Arnardottir, Harpa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Univ Akureyri, Sch Hlth Sci, Akureyri, Iceland.;Akureyri Hosp, Rehabil Unit, Akureyri, Iceland..
    Aflimanir ofan ökkla 2010-2019 vegna útæðasjúkdóms og/eða sykursýki: Aðdragandi og áhættuþættir2024In: Laeknabladid: The icelandic medical journal, ISSN 0023-7213, E-ISSN 1670-4959, Vol. 110, no 1, p. 20-27Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: No recent studies exist on lower extremity amputations (LLAs) in Iceland. The aim of this study was to investigate LLA incidence in Iceland 2010-2019 and preceding procedures in amputations induced by peripheral arterial disease (PAD) and diabetes mellitus (DM).

    MATERIAL AND METHODS: Retrospective study on clinical records of all patients (>18 years) who underwent LLA in Iceland's two main hospitals during 2010-2019. Patients were excluded if LLA was performed for reasons other than DM and/or PAD. Symptoms, medication and circulation assessment were recorded from first hospital visit due to symptoms, and prior to the last LLA, respectively. Previous arterial surgeries and amputations were also recorded.

    RESULTS: A total of 167 patients underwent LLA. Thereof, 134 (77 ± 11 years, 93 men and 41 woman) due to DM and/or PAD. The LLA-rate due to those diseases increased from 4.1/100,000 inhabitants in 2010-2013 to 6.7/100,000 in 2016-2019 (p=0,04). Risk factors were mainly hypertension, 84%, and smoking, 69%. Chronic limb -threatening ischemia induced 71% of first hospital visits. Revascularisations were performed (66% endovascular) in 101 patients. Non -diabetic patients were 52% and had statins less frequently prescribed than DM patients (26:45, p<0.001).

    CONCLUSION: DM and/or PAD are the leading causes of LLA in Iceland. Amputation rate increased during the period but is low in an international context. Amputation is most often preceded by arterial surgery. DM is present in almost half of cases, similar or less than in most other countries. Opportunities for improved prevention should aim on earlier diagnosis and preventive treatment of non -diabetic individuals with PAD.

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  • Ishengoma, Deus S.
    et al.
    Natl Inst Med Res, Dar Es Salaam, Tanzania.;Monash Univ, Fac Pharmaceut Sci, Melbourne, Australia.;Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02138 USA..
    Mandara, Celine I.
    Natl Inst Med Res, Dar Es Salaam, Tanzania..
    Madebe, Rashid A.
    Natl Inst Med Res, Dar Es Salaam, Tanzania..
    Warsame, Marian
    Gothenburg Univ, Gothenburg, Sweden..
    Ngasala, Billy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Child Health and Nutrition. Muhimbili Univ Hlth & Allied Sci, Sch Publ Hlth, Dept Parasitol, Dar Es Salaam, Tanzania..
    Kabanywanyi, Abdunoor M.
    Ifakara Hlth Inst, Dar Es Salaam, Tanzania..
    Mahende, Muhidin K.
    Ifakara Hlth Inst, Dar Es Salaam, Tanzania..
    Kamugisha, Erasmus
    Catholic Univ Hlth & Allied Sci, Bugando Med Ctr, Oncol Dept, Mwanza, Tanzania..
    Kavishe, Reginald A.
    Kilimanjaro Christian Med Univ Coll, Kilimanjaro Christian Med Ctr, Moshi, Tanzania..
    Muro, Florida
    Kilimanjaro Christian Med Univ Coll, Kilimanjaro Christian Med Ctr, Moshi, Tanzania..
    Mandike, Renata
    Minist Hlth, Natl Malaria Control Programme, Dodoma, Tanzania..
    Mkude, Sigsbert
    Minist Hlth, Natl Malaria Control Programme, Dodoma, Tanzania..
    Chacky, Frank
    Minist Hlth, Natl Malaria Control Programme, Dodoma, Tanzania..
    Njau, Ritha
    Fred Hutch Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA USA..
    Martin, Troy
    Fred Hutch Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA USA..
    Mohamed, Ally
    Minist Hlth, Natl Malaria Control Programme, Dodoma, Tanzania..
    Bailey, Jeffrey A.
    Brown Univ, Warren Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI USA..
    Fola, Abebe A.
    Brown Univ, Warren Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI USA..
    Microsatellites reveal high polymorphism and high potential for use in anti-malarial efficacy studies in areas with different transmission intensities in mainland Tanzania2024In: Malaria Journal, E-ISSN 1475-2875, Vol. 23, no 1, article id 79Article in journal (Refereed)
    Abstract [en]

    Background: Tanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of anti-malarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes, merozoite surface proteins 1 and 2 (msp1 and msp2), and replacing the glutamate-rich protein (glurp) gene with one of the highly polymorphic microsatellites in Plasmodium falciparum to adjust the efficacy of antimalarials in TES. This study assessed the polymorphisms of six neutral microsatellite markers and their potential use in TES, which is routinely performed in Tanzania.

    Methods: Plasmodium falciparum samples were obtained from four TES sentinel sites, Kibaha (Pwani), Mkuzi (Tanga), Mlimba (Morogoro) and Ujiji (Kigoma), between April and September 2016. Parasite genomic DNA was extracted from dried blood spots on filter papers using commercial kits. Genotyping was done using six microsatellites (Poly-alpha, PfPK2, TA1, C3M69, C2M34 and M2490) by capillary method, and the data were analysed to determine the extent of their polymorphisms and genetic diversity at the four sites.

    Results: Overall, 83 (88.3%) of the 94 samples were successfully genotyped (with positive results for >= 50.0% of the markers), and > 50.0% of the samples (range = 47.6-59.1%) were polyclonal, with a mean multiplicity of infection (MOI) ranging from 1.68 to 1.88 among the four sites. There was high genetic diversity but limited variability among the four sites based on mean allelic richness (R-S = 7.48, range = 7.27-8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (H-e = 0.83, range = 0.80-0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (F-ST) did not reveal population structure or clustering of parasites according to geographic origin. Of the six markers, Poly-alpha was the most polymorphic, followed by C2M34, TA1 and C3M69, while M2490 was the least polymorphic.

    Conclusion: Microsatellite genotyping revealed high polyclonality and genetic diversity but no significant population structure. Poly-alpha, C2M34, TA1 and C3M69 were the most polymorphic markers, and Poly-alpha alone or with any of the other three markers could be adopted for use in TES in Tanzania.

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  • Procopio, Noemi
    et al.
    Univ Cent Lancashire, Res Ctr Field Archaeol & Forens Taphon, Sch Law & Policing, Preston PR1 2HE, England..
    Sguazzi, Giulia
    Univ Piemonte Orientale, CRIMEDIM Ctr Res & Training Disaster Med Humanitar, Via Lanino 1, I-28100 Novara, Italy.;Univ Piemonte Orientale, Dept Hlth Sci, Via Solaroli 17, I-28100 Novara, Italy..
    Eriksson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer Immunotherapy.
    Ogbanga, Nengi
    Northumbria Univ, Fac Hlth & Life Sci Appl Sci, Forens Sci Res Grp, Newcastle Upon Tyne NE1 8ST, England..
    Mckell, Frazer C.
    Murdoch Univ, Sch Med Mol & Forens Sci, 90 South St, Murdoch, WA 6150, Australia..
    Newton, Eleanor P.
    Murdoch Univ, Sch Med Mol & Forens Sci, 90 South St, Murdoch, WA 6150, Australia..
    Magni, Paola A.
    Murdoch Univ, Sch Med Mol & Forens Sci, 90 South St, Murdoch, WA 6150, Australia..
    Bonicelli, Andrea
    Univ Cent Lancashire, Res Ctr Field Archaeol & Forens Taphon, Sch Law & Policing, Preston PR1 2HE, England..
    Gino, Sarah
    Univ Piemonte Orientale, Dept Hlth Sci, Via Solaroli 17, I-28100 Novara, Italy..
    Transferability of Human and Environmental Microbiome on Clothes as a Tool for Forensic Investigations2024In: Genes, ISSN 2073-4425, E-ISSN 2073-4425, Vol. 15, no 3, article id 375Article in journal (Refereed)
    Abstract [en]

    Considering the growing importance of microbiome analyses in forensics for identifying individuals, this study explores the transfer of the skin microbiome onto clothing, its persistence on fabrics over time, and its transferability from the environment and between different garments. Furthermore, this project compares three specific QIAGEN microbiome extraction kits to test their extraction efficiency on fabric samples. Additionally, this study aims to check if these extracts contain human DNA, providing a chance to obtain more information from the same evidence for personal identification. The results obtained show: (1) variations in the skin microbiome between the volunteers, potentially due to their different sex; (2) differences in microbial composition between worn and unworn clothing; (3) the influence of the environment on the microbial signature of unworn clothing; (4) the potential use of certain phyla as biomarkers to differentiate between worn and unworn garments, even over extended periods; (5) a tendency towards extraction biases in the QIAampMP (R) DNA microbiome kit among the three tested ones; and (6) none of the extraction kits allow for the typing of human genetic profiles suitable for comparison. In conclusion, our study offers supplementary insights into the potential utility of time-transferred microbiome analysis on garments for forensic applications.

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  • Public defence: 2024-05-03 13:15 101195, Ångströmlaboratoriet, Uppsala
    Suazo, Matías
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Observational Astronomy.
    Searching for Dyson spheres in the Milky Way2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The quest to find intelligent extraterrestrial life has captivated humanity for a long time, motivating the development of various strategies to search for signs of advanced civilizations. These strategies comprise multiple techniques and span different regions of the electromagnetic spectrum. One approach considers the existence of  Dyson spheres, one specific type of megastructure theorized by Freeman Dyson over sixty years ago. Dyson hypothesized that advanced civilizations would eventually outgrow their planetary resources and aim to collect the energy of their central star by building colossal structures to harness the star's energy. The potential existence of these structures represents a potential technosignature that might be hiding in large astronomical surveys, and this thesis revolves around exploring such a premise. First, we devote our search to assessing upper limits on the prevalence of Dyson spheres in the Milky Way by analyzing combined optical and mid-infrared photometric data. These upper limits are presented on the fraction of stars that may potentially host Dyson spheres and are model-dependent. We find robust limits of 1 over 100,000 stars for 300 K Dyson spheres at a 90% completion level within 100 pc. After that, we develop a pipeline especially tailored to identify potential Dyson sphere candidates in a sample of five million objects with available optical, near, and mid-infrared photometric data. This pipeline yields seven M dwarfs exhibiting anomalous infrared excess that deserve further analysis. Finally, we present an analysis of photometric and, in some cases, spectroscopic data on these seven objects, plus three additional sources sharing similar properties. The stellar parameters, derived from calibrated empirical relationships for M dwarfs, reveal no irregularities compared to the typical M dwarf population. While the infrared properties of our targets resemble, in some cases, those of young stars, spectroscopic data show no signs of youth usually observed for such objects. We still lack a clear explanation for the infrared excess of these stars, but we acknowledge that future follow-up observations could probe scenarios in which the infrared excess is due to circumstellar dust emission.

    List of papers
    1. Project Hephaistos - I. Upper limits on partial Dyson spheres in the Milky Way
    Open this publication in new window or tab >>Project Hephaistos - I. Upper limits on partial Dyson spheres in the Milky Way
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    2022 (English)In: Monthly notices of the Royal Astronomical Society, ISSN 0035-8711, E-ISSN 1365-2966, Vol. 512, no 2, p. 2988-3000Article in journal (Refereed) Published
    Abstract [en]

    Dyson spheres are hypothetical megastructures built by advanced extraterrestrial civilizations to harvest radiation energy from stars. Here, we combine optical data from Gaia DR2 with mid-infrared data from AllWISE to set the strongest upper limits to date on the prevalence of partial Dyson spheres within the Milky Way, based on their expected waste-heat signatures. Conservative upper limits are presented on the fraction of stars at G <= 21 that may potentially host non-reflective Dyson spheres that absorb 1-90 per cent of the bolometric luminosity of their host stars and emit thermal waste-heat in the 100-1000 K range. Based on a sample of approximate to 2.7 x 10(5) stars within 100 pc, we find that a fraction less than approximate to 2 x 10(-5) could potentially host similar to 300 K Dyson spheres at 90 per cent completion. These limits become progressively weaker for less complete Dyson spheres due to increased confusion with naturally occurring sources of strong mid-infrared radiation, and also at larger distances, due to the detection limits of WISE. For the similar to 2.9 x 10(8) stars within 5 kpc in our Milky Way sample, the corresponding upper limit on the fraction of stars that could potentially be similar to 300 K Dyson spheres at 90 per cent completion is less than or similar to 8 x 10(-4).

    Place, publisher, year, edition, pages
    Oxford University Press (OUP), 2022
    Keywords
    Extraterrestrial intelligence, infrared: stars
    National Category
    Astronomy, Astrophysics and Cosmology
    Identifiers
    urn:nbn:se:uu:diva-473193 (URN)10.1093/mnras/stac280 (DOI)000776894900003 ()
    Funder
    Swedish National Space Board
    Available from: 2022-04-27 Created: 2022-04-27 Last updated: 2024-03-13Bibliographically approved
    2. Project Hephaistos – II. Dyson sphere candidates from Gaia DR3, 2MASS, and WISE
    Open this publication in new window or tab >>Project Hephaistos – II. Dyson sphere candidates from Gaia DR3, 2MASS, and WISE
    (English)Manuscript (preprint) (Other academic)
    Keywords
    Extraterrestrial intelligence, infrared:stars, stars:low-mass
    National Category
    Astronomy, Astrophysics and Cosmology
    Research subject
    Astronomy and Astrophysics; Astronomy
    Identifiers
    urn:nbn:se:uu:diva-525985 (URN)
    Note

    Paper submitted to Monthly Notices of the Royal Astronomical Society

    Available from: 2024-04-02 Created: 2024-04-02 Last updated: 2024-04-11
    3. Project Hephaistos – III. Characterizing anomalous infrared sources identified as Dyson Sphere candidates
    Open this publication in new window or tab >>Project Hephaistos – III. Characterizing anomalous infrared sources identified as Dyson Sphere candidates
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

      

    Keywords
    Extraterrestrial intelligence, infrared:stars, stars:low-mass
    National Category
    Astronomy, Astrophysics and Cosmology
    Research subject
    Astronomy and Astrophysics; Astronomy
    Identifiers
    urn:nbn:se:uu:diva-525986 (URN)
    Available from: 2024-04-02 Created: 2024-04-02 Last updated: 2024-04-11
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  • Public defence: 2024-05-08 13:15 Lecture Hall IV, University Main Building, Uppsala
    Kåks, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, SWEDESD - Sustainability Learning and Research Centre.
    Contextualising a South African social innovation for maternal and child health to mothers with experiences of migration in Sweden2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Despite a universally accessible and high-quality welfare system, disparities in health and wellbeing persist between families who have migrated to Sweden and the native population. The South African Mentor Mother programme, a social innovation for maternal and child health among socially disadvantaged communities, was transferred and adapted to benefit mothers and pregnant women with experiences of migrating to Sweden.

    This thesis aims to explore the adaptation, implementation and further development of the South African Mentor Mother programme in two locations in Sweden, based on professional and lived experience among various groups of stakeholders.

    In Study I, three workshops and eleven interviews were held with stakeholders to explore central aspects of the adaptation process. These aspects entailed prioritising social determinants of health over health behaviour change, using indirect mechanisms and social ripples to achieve change, prioritising referring clients over intervening directly, recruiting peer supporters with competencies responding to a heterogeneous socio-cultural context, and allowing flexibility in programme content and methods.

    In Study II, nineteen interviews with different stakeholders and digital field logs of peer support meetings (n=1,294) were used to evaluate the implementations of the programme. Contextual factors of importance included institutional mistrust, gender norms, unpredictable funding, and the organisation's third sector affiliation. Peer supporters prioritised linking clients to welfare services over educational intervention components, and sometimes experienced blurring between professional and personal roles. Practical support and trustful relationships emerged as important entry points to support more sensitive issues. 

    In Study III, the photovoice method was used to conduct a focus group discussion and six interviews with Mentor Mothers and their coordinator in Gothenburg, exploring how they developed empowerment strategies perceived to be relevant, feasible and effective. These strategies consisted of various aspects of using both informative, practical, psychosocial and motivational support to meet community health and social needs.

    In Study IV, twenty-one interviews with Mentor Mothers, client mothers and other stakeholders were conducted to explore the emergence and management of mistrust in welfare services in Gothenburg. Mistrust was described to arise through rumours, unclear interactions with services, and lack of familiarity with the welfare system. Mentor Mothers used various strategies to build trusting relations with clients, which enabled them to promote institutional trust through information and humanisation of service providers.

    This thesis illustrates how innovative community-based solutions to complex societal problems can be transferred between contexts, implemented and further developed to ensure their relevance to the target group.

    List of papers
    1. Adapting a South African social innovation for maternal peer support to migrant communities in Sweden: a qualitative study
    Open this publication in new window or tab >>Adapting a South African social innovation for maternal peer support to migrant communities in Sweden: a qualitative study
    2022 (English)In: International Journal for Equity in Health, E-ISSN 1475-9276, Vol. 21, no 1, article id 88Article in journal (Refereed) Published
    Abstract [en]

    Introduction and aim Social and health disparities persist in Sweden despite a high quality and universally accessible welfare system. One way of bridging social gaps is through social innovations targeting the most vulnerable groups. The South African Philani model, a social innovation for peer support aimed at pregnant women and mothers of young children, was adapted to the local context in southern Sweden. This study aimed to document and analyze the process of adapting the Philani model to the Swedish context. Methods Eight semi-structured interviews and three workshops were held with eleven stakeholders and peer supporters in the implementing organization and its steering committee. The data were analyzed using thematic analysis. Results The analysis resulted in five main themes and fifteen sub-themes representing different aspects of how the peer support model was contextualized. The main themes described rationalizations for focusing on social determinants rather than health behaviors, using indirect mechanisms and social ripple effects to achieve change, focusing on referring clients to established public and civil society services, responding to a heterogeneous sociocultural context by recruiting peer supporters with diverse competencies, and having a high degree of flexibility in how contact was made with clients and how their needs were met. Conclusion The South African Philani model was contextualized to support socially disadvantaged mothers and expectant mothers among migrant communities in Sweden. In the process, adaptations of the intervention's overall focus, working methods, and recruitment and outreach strategies were motivated by the existing range of services, the composition of the target group and the conditions of the delivering organization. This study highlights various considerations that arise when a social innovation developed in a low- or middle-income context is implemented in a high-income context.

    Place, publisher, year, edition, pages
    Springer NatureSpringer Nature, 2022
    Keywords
    Health inequity, Paraprofessionals, Home visiting, Social determinants of health, Migration, Segregation, Social integration, Early childhood development, Social innovation
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-479897 (URN)10.1186/s12939-022-01687-4 (DOI)000814630700001 ()35733169 (PubMedID)
    Funder
    EU, Horizon 2020
    Available from: 2022-07-05 Created: 2022-07-05 Last updated: 2024-03-15Bibliographically approved
    2. Implementing a social innovation for community-based peer support for immigrant mothers in Sweden: a mixed-methods process evaluation
    Open this publication in new window or tab >>Implementing a social innovation for community-based peer support for immigrant mothers in Sweden: a mixed-methods process evaluation
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    2024 (English)In: Frontiers In Public Health, ISSN 2296-2565, Vol. 11, article id 1332738Article in journal (Refereed) Published
    Abstract [en]

    Introduction: A South African social innovation based on peer support for mothers was contextualized in southern Sweden. The objective of the project was to support expectant women and mothers of young children in immigrant communities to access public services that would benefit maternal and child health. This study aimed to assess how the intervention was implemented, what the contextual barriers and facilitators were, and how the implementation was perceived by those who delivered and received it.

    Methods: The study used mixed methods with a convergent parallel design and followed the Medical Research Council guidance on process evaluations of complex interventions. Semi-structured interviews (n = 19) were conducted with peer supporters, client mothers, and key stakeholders involved in the intervention. The qualitative data were analyzed using content analysis. Quantitative data on peer supporters' activities were collected during contacts with client mothers and were presented descriptively.

    Results: The five peer supporters had 1,294 contacts with client mothers, of which 507 were first-time contacts. The reach was perceived as wide, and the dose of the intervention was tailored to individual needs. Barriers to implementation included community mistrust of social services, norms on gender roles and parenting, and funding challenges. The implementation was facilitated by the organization's reputation, network, experience, and third-sector affiliation. Peer supporters tended to prioritize linking clients to other services over the educational components of the intervention, sometimes doing more than what was originally planned. Implementation strategies used included building trust, using multiple outreach venues, using internal support structures, and providing practical assistance as an entry point to comprehensive psychosocial support. The personal connection between peer supporters and clients was highly valued, and the building of relationships enabled them to address sensitive topics. Peer supporters sometimes experienced a blurred line between professional and personal roles.

    Conclusions: Peer supporters used a variety of strategies to navigate identified barriers and facilitators. Trust was central both as a contextual factor and a strategy for implementation. It is valuable to maintain a balance between flexibility and adherence to the function of peer supporters. Further research is needed to evaluate the effects of the intervention.

    Place, publisher, year, edition, pages
    Frontiers Media S.A., 2024
    Keywords
    social innovation, peer support, process evaluation, mixed-methods, parents, children, maternal and child health
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology Social Work
    Identifiers
    urn:nbn:se:uu:diva-522456 (URN)10.3389/fpubh.2023.1332738 (DOI)001148794600001 ()38283291 (PubMedID)
    Funder
    Uppsala University
    Available from: 2024-02-07 Created: 2024-02-07 Last updated: 2024-03-15Bibliographically approved
    3. Empowerment strategies of the Mentor Mother peer support program among immigrant mothers in Sweden: a Photovoice study
    Open this publication in new window or tab >>Empowerment strategies of the Mentor Mother peer support program among immigrant mothers in Sweden: a Photovoice study
    (English)Manuscript (preprint) (Other academic)
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-524183 (URN)
    Available from: 2024-02-29 Created: 2024-02-29 Last updated: 2024-03-15
    4. Mentor Mothers as trust brokers between immigrant communities and the Swedish welfare system: A qualitative study
    Open this publication in new window or tab >>Mentor Mothers as trust brokers between immigrant communities and the Swedish welfare system: A qualitative study
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-524184 (URN)
    Available from: 2024-02-29 Created: 2024-02-29 Last updated: 2024-03-15
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  • Rystedt, Einar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical geriatrics.
    Moren, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Tedim Cruz, Vitor
    Serv Neurol, Unidade Local Saude Matosinhos, Matosinhos, Portugal.;Univ Porto, EPIUnit, Inst Saude Publ, Porto, Portugal.;Lab Invest Integrat & Translac Saude Populac ITR, Porto, Portugal..
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Molecular Geriatrics. Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada.;Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Dept Med & Lab Med, Toronto, ON, Canada.;Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Dept Pathobiol, Toronto, ON, Canada..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical geriatrics.
    Lunet, Nuno
    Univ Porto, EPIUnit, Inst Saude Publ, Porto, Portugal.;Lab Invest Integrat & Translac Saude Populac ITR, Porto, Portugal.;Univ Porto, Dept Ciencias Saude Publ & Forenses & Educ Med, Fac Med, Porto, Portugal..
    Pais, Joana
    Univ Porto, EPIUnit, Inst Saude Publ, Porto, Portugal.;Lab Invest Integrat & Translac Saude Populac ITR, Porto, Portugal..
    Ruano, Luis
    Univ Porto, EPIUnit, Inst Saude Publ, Porto, Portugal.;Lab Invest Integrat & Translac Saude Populac ITR, Porto, Portugal.;Univ Porto, Dept Ciencias Saude Publ & Forenses & Educ Med, Fac Med, Porto, Portugal.;Ctr Hosp Entre Douro & Vouga, Serv Neurol, Santa Maria Feira, Portugal..
    Westman, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Validation of a web-based self-administered test for cognitive assessment in a Swedish geriatric setting2024In: PLOS ONE, E-ISSN 1932-6203, Vol. 19, no 2, article id e0297575Article in journal (Refereed)
    Abstract [en]

    Computerized cognitive tests have the potential to cost-effectively detect and monitor cognitive impairments and thereby facilitate treatment for these conditions. However, relatively few of these tests have been validated in a variety of populations. Brain on Track, a self-administered web-based test, has previously been shown to have a good ability to differentiate between healthy individuals and patients with cognitive impairment in Portuguese populations. The objective of this study was to validate the differential ability and evaluate the usability of Brain on Track in a Swedish memory clinic setting. Brain on Track was administered to 30 patients with mild cognitive impairment/mild dementia and 30 healthy controls, all scheduled to perform the test from home after one week and after three months. To evaluate the usability, the patient group was interviewed after completion of the testing phase. Patients scored lower than healthy controls at both the first (median score 42.4 vs 54.1, p<0.001) and the second test (median score 42.3 vs 55.0, p<0.001). The test-retest intra-class correlation was 0.87. A multiple logistic regression model accounting for effects of age, gender and education rendered an ability of Brain on Track to differentiate between the groups with an area under the receiver operation characteristics curve of 0.90 for the first and 0.88 for the second test. In the subjective evaluation, nine patients left positive comments, nine were negative whereas five left mixed comments regarding the test experience. Sixty percent of patients had received help from relatives to log on to the platform. In conclusion, Brain on Track performed well in differentiating healthy controls from patients with cognitive impairment and showed a high test-retest reliability, on par with results from previous studies. However, the substantial proportion of patients needing help to log in could to some extent limit an independent use of the platform.

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  • Lappalainen, Johanna
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Civil and Industrial Engineering.
    The opportunities intangible assets generate for forest management: A case study of a service company from a disruptive innovation perspective2024Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Intangible assets are gaining market share in forest management and the economy. These solutions can be related to achieving carbon neutrality and creating services that incumbent forest companies do not provide.Incumbent companies may see the market changes and react to those. However, to avoid losing the market-leading position, incumbent companies can use disruptive innovation theory as a framework to evaluate the possible disruption. Moreover, the interviews and document analyses supported the framework usage in service innovation.Industry 4.0 has changed forest management with BigData and artificial intelligence technology and changed service management. Forests can be scanned with machines; for example, carbon sequestration can be calculated based on data and create a service for less-demand customers and niche markets. Intangible innovations have a field to serve these low-end consumers, and there is a potential for these markets to grow exceedingly and attract the main customers.

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  • Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Child Health and Nutrition. Karolinska Institutet and Uppsala University, Stockholm, Sweden;Makerere University, Kampala, Uganda.
    Embedded implementation research in programming at scale: the new normal to be!2024In: BMC Pediatrics, E-ISSN 1471-2431, Vol. 23, no SUPPL 1, article id 650Article in journal (Other academic)
    Abstract [en]

    If you want to run faster, don't just buy a new pair of shoes; also consider your training methods and where you run.This supplement examines six countries that have run faster than others in reducing under-five mortality, taking an implementation research approach, with country case studies done with local researchers and local institutions. Key generalizable learnings are to choose and adapt implementation strategies to context, design strategies to target the most vulnerable, systematically learn from implementation experience, and to leverage non-health-sector contributions.Embedding implementation research in programming has the potential to greatly improve and accelerate the contextualization and implementation of evidence-based child survival interventions to improve equity in coverage and overall effectiveness in reducing under-five mortality. It is now time to build such capacity in local institutions at scale, and incentives for concerned stakeholders to make this the new normal. Regional institutions should now take the lead in making this happen, not just in individual institutions and countries, but across entire regions, supported by global partners.Trial registration N/A.

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  • Ablikim, M.
    et al.
    Inst High Energy Phys, Beijing 100049, Peoples R China.
    Adlarson, Patrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Johansson, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Kupse, A.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy. Natl Ctr Nucl Res, PL-02093 Warsaw, Poland..
    Schönning, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Thoren, V.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Wolke, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Zu, J.
    State Key Lab Particle Detect & Elect, Beijing 100049, Peoples R China;Univ Sci & Technol China, Hefei 230026, Peoples R China.
    First observation of Λ+ c → ΛK+ π0 and evidence of Λ+ c → ΛK+ π + π -2024In: Physical Review D: covering particles, fields, gravitation, and cosmology, ISSN 2470-0010, E-ISSN 2470-0029, Vol. 109, no 3, article id 032003Article in journal (Refereed)
    Abstract [en]

    We present the first observation of the singly Cabibbo-suppressed decay Lambda thorn c ->Lambda K thorn pi 0with asignificance of5.7 sigma and the first evidence of Lambda thorn c ->Lambda K thorn pi thorn pi-decay with a significance of3.1 sigma,basedone thorn e-annihilation data recorded by the BESIII detector at the BEPCII collider. The data correspond to anintegrated luminosity of6.4fb-1, in the center-of-mass energy range from 4.600 to 4.950 GeV. Wedetermine the branching fractions of Lambda thorn c ->Lambda K thorn pi 0and Lambda thorn c ->Lambda K thorn pi thorn pi-relative to their Cabibbo-favored counterparts to beBo Lambda thorn c ->Lambda K thorn pi 0 thorn Bo Lambda thorn c ->Lambda pi thorn pi 0 thorn 1/4o2.090.39stat0.07syst thorn x10-2andBo Lambda thorn c ->Lambda K thorn pi thorn pi- thorn Bo Lambda thorn c ->Lambda pi thorn pi thorn pi- thorn 1/4o1.130.41stat0.06syst thorn x10-2, respectively. Moreover, by combining our measured result with theworld average ofBo Lambda thorn c ->Lambda pi thorn pi 0 thorn , we obtain the branching fractionBo Lambda thorn c ->Lambda K thorn pi 0 thorn 1/4o1.490.27stat0.05syst0.08ref thorn x10-3. This result significantly departs from theoretical predictionsbased on quarkSUo3 thorn flavor symmetry, which is underpinned by the presumption of meson pairS-waveamplitude dominance

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  • Mossberg, Rasmus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Cent Sjukhuset Karlstad, Reg Varmland, Centralsjukhuset Karlstad, Rosenborgsgatan 9, S-65230 Karlstad, Sweden..
    Ahlström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Falu Lasarett, Healthcare Reg Dalarna, Nissers Vag 3, S-79182 Falun, Sweden..
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    A nationwide cohort study on the association between intensive care treatments and mental distress linked psychiatric disorders2024In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 4519Article in journal (Refereed)
    Abstract [en]

    Given the psychic strain patients experience in the intensive care unit (ICU), a potential risk of mental disorders has been suggested. However, the effects of intensive care treatment per se are unknown. We investigated whether the level of intensive care treatments is an independent risk factor for developing long-term mental disorders after intensive care. In a national cohort of adult ICU patients we combined data on diagnoses, treatment, and causes of death. We defined extensive ICU treatment as being treated with invasive ventilation for > 24 h, continuous renal replacement therapy, or both. The primary outcome was incident mental disorder 1 year after ICU admission. Extensive ICU treatment was found to be associated with a decreased risk of developing a mental disorder >= 1 year after ICU admission (HR 0.90, 95% CI 0.82-0.99, p = 0.04), and increasing severity of acute illness (HR 1.18, 95% CI 1.06-1.32, p < 0.001) were associated with an increased risk of mental disorders. Because death acted as a competing risk for mental illness, mortality might help explain the apparent protective effect of extensive ICU care. Trial registration Clinical Trials Registry (Identification number NCT05137977). Registered 16 November 2021. As a registry trial the patients were already included at the trial registration i.e. it was retrospectively registered.

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  • Ablikim, M.
    et al.
    Inst High Energy Phys, Beijing 100049, Peoples R China.
    Adlarson, Patrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Johansson, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Kupsc, Andrzej
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics. Natl Ctr Nucl Res, PL-02093 Warsaw, Poland..
    Schönning, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Thoren, V.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Wolke, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Zu, J.
    State Key Lab Particle Detect & Elect, Beijing 100049, Peoples R China;Univ Sci & Technol China, Hefei 230026, Peoples R China.
    Search for the light hadron decay χc1(3872) → π+π-η2024In: Physical Review D: covering particles, fields, gravitation, and cosmology, ISSN 2470-0010, E-ISSN 2470-0029, Vol. 109, no 1, article id L011102Article in journal (Refereed)
    Abstract [en]

    With a data sample corresponding to an integrated luminosity of 11.5 fb(-1) collected with the BESIII detector operating at the BEPCII storage ring, for the first time the light hadron decay chi(c1()3872)->pi(+)pi(-)eta is searched for. While no significant signal is observed, the upper limits at the 90% confidence level for sigma[e(+)e(-)->gamma chi(c1)(3872)]B[chi(c1)(3872)->pi(+)pi(-)eta] at center of mass energies from 4.13 GeV to 4.34 GeV are determined. By normalizing to the chi(c1)(3872)->pi(+)pi(-)J/psi decay channel, a 90% confidence level upper limit for the branching fraction ratio R=B[chi(c1)(3872)->pi(+)pi(-)eta]/B[chi(c1)(3872)->pi(+)pi(-)J/psi]<0.12 is given. These measurements provide important inputs for understanding the internal structure of the chi(c1)(3872) resonance

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  • Höglund, Andrey
    et al.
    Stockholm Univ, Dept Environm Sci, Sci Life Lab, Stockholm, Sweden..
    Henriksen, Rie
    Linköping Univ, AVIAN Behav Genom & Physiol Grp, Linköping, Sweden..
    Churcher, Allison M.
    Umeå Univ, Dept Mol Biol, NBIS, Umeå, Sweden..
    Guerrero-Bosagna, Carlos M.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Physiology and Environmental Toxicology.
    Martínez Barrio, Álvaro
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johnsson, Martin
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Jensen, Per
    Linköping Univ, AVIAN Behav Genom & Physiol Grp, Linköping, Sweden..
    Wright, Dominic
    Linköping Univ, AVIAN Behav Genom & Physiol Grp, Linköping, Sweden..
    The regulation of methylation on the Z chromosome and the identification of multiple novel Male Hyper-Methylated regions in the chicken2024In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 20, no 3, article id e1010719Article in journal (Refereed)
    Abstract [en]

    DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. To investigate how variation in DNA methylation is regulated on the Z chromosome we utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals. The relatively large numbers of individuals allowed us to identify additional genomic MHM regions on the Z chromosome that were significantly differentially methylated between the sexes. These regions appear to down-regulate local gene expression in males, but not remove it entirely (unlike the lncRNAs identified in the initial MHM regions). These MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes. In addition, trans effect hotspots were also identified that were based on the autosomes but affected the Z, and also that were based on the Z chromosome but that affected autosomal DNA methylation regulation. In addition, quantitative trait loci (QTL) that regulate variation in methylation on the Z chromosome, and those loci that regulate methylation on the autosomes that derive from the Z chromosome were mapped. Trans-effect hotspots were also identified that were based on the autosomes but affected the Z, and also one that was based on the Z chromosome but that affected both autosomal and sex chromosome DNA methylation regulation. We show that both cis and trans loci that originate from the Z chromosome never exhibit an interaction with sex, whereas trans loci originating from the autosomes but affecting the Z chromosome always display such an interaction. Our results highlight how additional MHM regions are actually present on the Z chromosome, and they appear to have smaller-scale effects on gene expression in males. Quantitative variation in methylation is also regulated both from the autosomes to the Z chromosome, and from the Z chromosome to the autosomes. DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. We utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals, to investigate the role that methylation plays in regulating gene expression on the Z chromosome. Our results highlight how additional MHM regions are actually present on the Z chromosome, and they appear to have smaller-scale effects on gene expression in males. Quantitative variation in methylation is also regulated both from the autosomes to the Z chromosome, and from the Z chromosome to the autosomes. In addition, these MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes.

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  • Borisov, Vladislav
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Salehi, Nastaran
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Pereiro, Manuel
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Delin, Anna
    AlbaNova Univ Ctr, KTH Royal Inst Technol, Sch Engn Sci, Dept Appl Phys, SE-10691 Stockholm, Sweden.;KTH Royal Inst Technol, Swedish E Sci Res Ctr, SeRC, SE-10044 Stockholm, Sweden.;KTH Royal Inst Technol, Wallenberg Initiat Mat Sci Sustainabil WISE, SE-10044 Stockholm, Sweden..
    Eriksson, Olle
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Dzyaloshinskii-Moriya interactions, Néel skyrmions and V4 magnetic clusters in multiferroic lacunar spinel GaV4S82024In: npj Computational Materials, E-ISSN 2057-3960, Vol. 10, no 1, article id 53Article in journal (Refereed)
    Abstract [en]

    Using ab initio density functional theory with static mean-field correlations, we calculate the Heisenberg and Dzyaloshinskii-Moriya interactions (DMI) for an atomistic spin Hamiltonian for the lacunar spinel, GaV4S8. The parameters describing these interactions are used in atomistic spin dynamics and micromagnetic simulations. The magnetic properties of the lacunar spinel GaV4S8, a material well-known from experiment to host magnetic skyrmions of Neel character, are simulated with these ab initio calculated parameters. The Dzyaloshinskii-Moriya contribution to the micromagnetic energy is a sum of two Lifshitz invariants, supporting the formation of Neel skyrmions and its symmetry agrees with what is usually expected for C-3 nu-symmetric systems. There are several conclusions one may draw from this work. One concerns the quantum nature of the magnetism, where we show that the precise magnetic state of the V-4 cluster is crucial for understanding quantitatively the magnetic phase diagram. In particular, we demonstrate that a distributed-moment state of each V4 cluster explains well a variety of properties of GaV4S8, such as the band gap, observed Curie temperature and especially the stability of Neel skyrmions in the experimentally relevant temperature and magnetic-field range. In addition, we find that electronic correlations change visibly the calculated value of the DMI.

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  • Aad, G.
    et al.
    Aix Marseille Univ, CNRS, IN2P3, CPPM, Marseille, France.
    Asimakopoulou, E. M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Bergeås Kuutmann, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Dimitriadi, Christina
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics. Univ Bonn, Phys Inst, Bonn, Germany..
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellajosyula, Venugopal
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Gonzalez Suarez, Rebeca
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Mathisen, T.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Oerdek, S.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Steentoft, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Sunneborn Gudnadottir, Olga
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    CERN, Geneva, Switzerland.
    Searches for new phenomena in events with two leptons, jets, and missing transverse momentum in 139 fb-1 of √s=13 TeV pp collisions with the ATLAS detector2023In: European Physical Journal C, ISSN 1434-6044, E-ISSN 1434-6052, Vol. 83, no 6, article id 515Article in journal (Refereed)
    Abstract [en]

    Searches for new phenomena inspired by super-symmetry in final states containing an e(+) e(-) or mu(+) mu(-) pair, jets, and missing transverse momentum are presented. These searches make use of proton-proton collision data with an integrated luminosity of 139 fb(-1), collected during 2015-2018 at a centre-of-mass energy root s = 13 TeVby the ATLAS detector at the Large Hadron Collider. Two searches target the pair production of charginos and neutralinos. One uses the recursive-jigsaw reconstruction technique to follow up on excesses observed in 36.1 fb(-1) of data, and the other uses conventional event variables. The third search targets pair production of coloured supersymmetric particles (squarks or gluinos) decaying through the next-to-lightest neutralino ((chi) over tilde (0)(2)) via a slepton ((l) over tilde) or Z boson into l(+) l(-) (chi) over tilde (0)(1), resulting in a kinematic endpoint or peak in the dilepton invariant mass spectrum. The data are found to be consistent with the Standard Model expectations. Results are interpreted using simplified models and exclude masses up to 900 GeV for electroweakinos, 1550 GeV for squarks, and 2250 GeV for gluinos.

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  • von Beek, Christopher
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fahlgren, Anna
    Umeå Univ, Umeå Ctr Microbial Res UCMR, Dept Mol Biol, Lab Mol Infect Med Sweden MIMS, Umeå, Sweden..
    Geiser, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Di Martino, Maria Letizia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lindahl, Otto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Prensa, Grisna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mendez-Enriquez, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Eriksson, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hallgren, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fällman, Maria
    Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sellin, Mikael E.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    A two-step activation mechanism enables mast cells to differentiate their response between extracellular and invasive enterobacterial infection2024In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 904Article in journal (Refereed)
    Abstract [en]

    Mast cells localize to mucosal tissues and contribute to innate immune defense against infection. How mast cells sense, differentiate between, and respond to bacterial pathogens remains a topic of ongoing debate. Using the prototype enteropathogen Salmonella Typhimurium (S.Tm) and other related enterobacteria, here we show that mast cells can regulate their cytokine secretion response to distinguish between extracellular and invasive bacterial infection. Tissue-invasive S.Tm and mast cells colocalize in the mouse gut during acute Salmonella infection. Toll-like Receptor 4 (TLR4) sensing of extracellular S.Tm, or pure lipopolysaccharide, causes a modest induction of cytokine transcripts and proteins, including IL-6, IL-13, and TNF. By contrast, type-III-secretion-system-1 (TTSS-1)-dependent S.Tm invasion of both mouse and human mast cells triggers rapid and potent inflammatory gene expression and >100-fold elevated cytokine secretion. The S.Tm TTSS-1 effectors SopB, SopE, and SopE2 here elicit a second activation signal, including Akt phosphorylation downstream of effector translocation, which combines with TLR activation to drive the full-blown mast cell response. Supernatants from S.Tm-infected mast cells boost macrophage survival and maturation from bone-marrow progenitors. Taken together, this study shows that mast cells can differentiate between extracellular and host-cell invasive enterobacteria via a two-step activation mechanism and tune their inflammatory output accordingly.

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