Publikationer från Uppsala Universitet
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    Giant transposons promote strain heterogeneity in a major fungal pathogen

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    Fungal infections are difficult to prevent and treat in large part due to strain heterogeneity, which confounds diagnostic predictability. Yet, the genetic mechanisms driving strain-to-strain variation remain poorly understood. Here, we determined the extent to which Starships—giant transposons capable of mobilizing numerous fungal genes—generate genetic and phenotypic variability in the opportunistic human pathogen Aspergillus fumigatus. We analyzed 519 diverse strains, including 11 newly sequenced with long-read technology and multiple isolates of the same reference strain, to reveal 20 distinct Starships that are generating genomic heterogeneity over timescales relevant for experimental reproducibility. Starship-mobilized genes encode diverse functions, including known biofilm-related virulence factors and biosynthetic gene clusters, and many are differentially expressed during infection and antifungal exposure in a strain-specific manner. These findings support a new model of fungal evolution wherein Starships help generate variation in genome structure, gene content, and expression among fungal strains. Together, our results demonstrate that Starships are a previously hidden mechanism generating genotypic and, in turn, phenotypic heterogeneity in a major human fungal pathogen. IMPORTANCE No “one size fits all” option exists for treating fungal infections in large part due to genetic and phenotypic variability among strains. Accounting for strain heterogeneity is thus fundamental for developing efficacious treatments and strategies for safeguarding human health. Here, we report significant progress toward achieving this goal by uncovering a previously hidden mechanism generating heterogeneity in the human fungal pathogen Aspergillus fumigatus: giant transposons, called Starships, that span dozens of kilobases and mobilize fungal genes as cargo. By conducting a systematic investigation of these unusual transposons in a single fungal species, we demonstrate their contributions to population-level variation at the genome, pangenome, and transcriptome levels. The Starship compendium we develop will not only help predict variation introduced by these elements in laboratory experiments but will serve as a foundational resource for determining how Starships impact clinically relevant phenotypes, such as antifungal resistance and pathogenicity

    The Stokes problem with Navier boundary conditions in irregular domains

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    We consider the steady Stokes equations supplemented with Navier boundary conditions including a non-negative friction coefficient. We prove maximal regularity estimates (including the prominent spaces W-1,W- p and W-2,W- p for 1 < p < infinity for the velocity field) in bounded domains of minimal regularity. Interestingly, exactly one derivative more is required for the local boundary charts compared to the case of no-slip boundary conditions. We demonstrate the sharpness of our results by a propos examples

    In the Name of the Nation : The Strategic Use of Catholicism in Vox’s Populist Discourse

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    This thesis examines how Vox, Spain’s far-right populist party, strategically employs Catholic symbols and narratives in its political discourse to shape national belonging and draw moral boundaries. Grounded in a constructivist and interpretive framework, it analyzes how religious rhetoric frames debates on immigration, gender, education, and national identity, portraying Catholicism as a cultural identity under threat from secularism, multiculturalism, and liberal ideologies. Using qualitative case study methods and critical discourse analysis of selected speeches and online materials, the thesis identifies how symbolic references —such as the Reconquista and the Christian family— are deployed to present political opponents as threats and reinforce a nationalist moral order. Findings indicate that Vox mobilizes Catholic themes less as expressions of belief than as emotionally resonant, performative tactics that simplify complex social issues into binaries of good versus evil, and belonging versus exclusion. This case contributes to broader discussions on religion in contemporary populist politics and the evolving nature of religious identity in secular democracies, showing how religion is mobilized to define, divide, and emotionally engage “the people.

    Operational optimization of hydrogen gas production. : A study based on the Swedish energy system

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    Stabiliteten i Sveriges energisystem utmanas till följd av utbyggnaden av förnybara energikällor.Stora skillnader i elpris tyder på systeminstabilitet, även om dessa skillnader går att utnyttja för eko-nomisk vinst. Vätgasproduktion genom elektrolys med protonbytarmembran (PEM) kan användastillsammans med intermittenta energislag i hybridparker. Den snabba ramptiden hos PEM ger möj-ligheten till snabb respons på förändringar i elpriser och egenproducerad el. Användningen av enoptimeringsmodell för vätgasproduktion med avseende på elpriser och egenproducerad el kan mini-mera elförsäljning till ogynnsamma elpriser, vilket maximera värde. Detta hjälper även till med attstabilisera elnätet och synergerar med stödtjänster. Ett dynamiskt driftsätt gav alltid högre intäkterjämfört med statisk drift men slitaget det har på elektrolysören och kostnaderna det medför är intekonstaterade.The Swedish energy system faces major challenges regarding technical instability in the electricalgrid due to increased development of renewable energy. Large fluctuations in energy prices may onone hand indicate system instability. On the other hand, they can create opportunities to capitalize ontheir volatility. Hydrogen production through proton exchange membrane (PEM) electrolysis can beutilized in tandem with intermittent energy sources in so-called hybrid parks. The short ramp timesof PEM enable quick responses to the fluctuations in both electricity prices and energy production.Using a Receding Horizon Control (RHC) model, the production of hydrogen in regard to electri-city prices and on-site power production can be optimized in order to minimize selling electricityat low unfavorable prices; thus, maximizing value. This also helps stabilize the power grid and sy-nergizes with ancillary services. Dynamic operation always resulted in increased revenue comparedto steady-state operation. However, the rate of degradation in the elecrolyser caused by changingproduction-level remains unknow

    The Coordinator as a Boundary Worker : A Study of Coordinators’ Perspectives on Collaboration within Social Intervention Teams

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    Sociala insatsgrupper (SIG) är en samverkansmodell i Sverige som syftar till att förebygga kriminalitet bland ungdomar i riskzon samt att stödja ungdomar som redan befinner sig i kriminella livsstilar att lämna dessa. Syftet med denna studie är att undersöka SIG-samordnares erfarenheter av att ingå i operativa grupper, med fokus på  att identifiera utvecklingsområden och fungerande metoder för samverkan. Detta är särskilt relevant i ett läge där det brottsförebyggande arbetet är omfattande och därav står högt på den politiska agendan. Empiriskt material består av sex semistrukturerade intervjuer med samordnare från olika kommuner i Sverige. Materialet har analyserats med tematisk analys och tolkats genom nyinstitutionell teori och teorin om gränsarbete. Resultatet visar att samordnare har en övergripande positiv bild av samverkan inom SIG, men att rollen ofta präglas av ett omfattande och ibland ensamt ansvar. Tillit mellan professionerna och en nära relation till ungdomarna framstår som centrala framgångsfaktorer. Samverkan underlättas när professionerna verkar under samma organisatoriska tak och har etablerade relationer sinsemellan. I de operativa grupperna, där det praktiska arbetet kring ungdomarna sker, blir denna närhet särskilt viktig för att skapa samsyn och effektivitet. Samtidigt pekar samordnarna på utmaningar relaterade till organisatoriska skillnader, resursbrist och varierande engagemang.

    GLIM consensus approach to diagnosis of malnutrition : A 5-year update

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    Background The Global Leadership Initiative on Malnutrition (GLIM) introduced an approach for malnutrition diagnosis in 2019 that comprised screening followed by assessment of three phenotypic criteria (weight loss, low body mass index [BMI], and low muscle mass) and two etiologic criteria (reduced food intake/assimilation and inflammation/disease burden). This planned update reconsiders the GLIM framework based on published knowledge and experience over the past 5 years. Methods A working group (n = 43 members) conducted a literature search spanning 2019–2024 using the keywords “Global Leadership Initiative on Malnutrition or GLIM.” Prior GLIM guidance activities for using the criteria on muscle mass and inflammation were reviewed. Successive rounds of revision and review were used to achieve consensus. Results More than 400 scientific reports were published in peer-reviewed journals, forming the basis of 10 systematic reviews, some including meta-analyses of GLIM validity that indicate strong construct and predictive validity. Limitations and future priorities are discussed. Working group findings suggest that assessment of low muscle mass should be guided by experience and available technological resources. Clinical judgment may suffice to evaluate the inflammation/disease burden etiologic criterion. No revisions of the weight loss, low BMI, or reduced food intake/assimilation criteria are suggested. After two rounds of review and revision, the working group secured 100% agreement with the conclusions reported in the 5-year update. Conclusion Ongoing initiatives target priorities that include malnutrition risk screening procedures, GLIM adaptation to the intensive care setting, assessment in support of the reduced food intake/assimilation criterion, and determination of malnutrition in obesity.De två första författarna delar förstaförfattarskapet</p

    Pharmaceutical residues in sludge-fertilized farmland – occurrence and risks

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    Rapporten sammanfattar resultaten från ett projekt med tre delstudier som undersökte 1) om spridning av kommunalt avloppsslam orsakar förhöjda halter av läkemedelsrester i odlingsjordar samt hur höga miljöriskerna är, 2) om det sker någon nedbrytning av läkemedelsrester i jorden, samt 3) om slamgödslad åkermark läcker läkemedelsrester vid regn och därmed innebär en miljörisk för omgivande vatten.  Studien genomfördes på, och med jord från, försöksfälten i Lanna (Lidköping), Igelösa (Lund) och Ultuna (Uppsala) där avloppsslam spridits under lång tid (23, 40 respektive 65 år). Analyser gjordes på slam, jordprover samt lakvatten. Analyser gjordes först för ett brett spektrum av läkemedel som används i Sverige (148 substanser) och därefter för läkemedels­rester som oftast påvisas i avloppsvatten och slam i Sverige (upp till 34 substanser). Jord och slam analyserades även för metaller med ambitionen att hitta en korrelation mellan metaller och läkemedelsrester. Ingen korrelation kunde dock upprättas på grund av låga detektionsnivåer gällande läkemedelsrester.   Delstudie 1: Resultaten visar att majoriteten av läkemedelsrester i jordarna var under detektionsnivå. Detta trots att försöksfälten fått slamgivor upp till fem gånger högre än medelgivor för svenska förhållanden. Spårkoncentrationer om 1–48 ng/g TS för citalopram, oxazepam, propanolol, sertralin och venlafaxin uppmättes några år efter senaste slamspridningen. Triklokarban var den substans som återfanns i högst koncentration (160 ng/g TS). För majoriteten av ämnen går det inte att påvisa ackumulering, men det går heller inte att utesluta den. För samma fem ämnen som nämns ovan (citalopram, sertralin, oxazepam, propanolol och venlafaxin) sker det sannolikt en ackumulering enligt den här studiens teoretiska ansats. För att kunna utesluta eller bekräfta ackumulering behövs känsligare analyser som kan mäta de koncentrationer som förväntas finnas i jorden.  På Igelösafältet, för de delar som slamgödslats med i snitt 1 ton TS/ha och år sedan 1981, kunde inga läkemedelsrester detekteras. Dock hittades triklokarban som är ett antibakteriellt ämne som tidigare användes i hygienprodukter som tvål och duschkräm. Eftersom inga läkemedelsrester av terapeutiska mål detekterades i jorden från den här delen av Igelösafältet så gick det inte att bekräfta någon läkemedelsresters ackumulering på detta fält.   Delstudie 2: Det var svårt att dra slutsatser kring nedbrytning av läkemedelsrester i jord då inblandningen av slam i jorden ledde till så stor utspädning att samtliga läkemedelsrester hamnade under detektionsgränsen, med undantag för sertralin och citalopram. Citalopram detekterades i jorden både före och efter sl­amspridning, vilket kan tyda på ackumulering och gör slutsatser kring nedbrytning svåra. En teoretisk beräkning med första ordningens nedbrytningskinetik tyder på att ciprofloxacin, ketoconazol och sertralin bryts ned i jorden efter inblandning.   Delstudie 3: Vid bevattning av slamgödslade sand- och lerlysimetrar (jordkolonner) detekterades följande substanser i lakvattnet: karbamazepin, citalopram, diklofenak, ibuprofen, metoprolol och paracetamol. En kort tidsperiod mellan slamtillförsel och regn (1–3 dagar) orsakade betydande urlakning av läkemedelsrester från både sand- och lerlysimetrar, medan längre tidsintervall mellan slamgödsling och regn (1 månad) inte ledde till mätbar urlakning, med undantag för paracetamol. Rörligheten av paracetamol och diklofenak var högre i sand än i lera, vilket skulle kunna bero på högre adsorption och nedbrytning i leran än i sanden. Ingen korrelation mellan gödslingsmängd och läkemedelsrester sågs. Både diklofenak och paracetamol återfanns i relativt höga koncentrationer (14–370 ng/l respektive 7–370 ng/l) i lakvattnet, vilket därför skulle kunna utgöra en miljörisk för närliggande yt- och grundvatten.  This report summarises the results from a project involving three sub-studies investigating:  1) whether the spreading of municipal sewage sludge causes elevated levels of pharmaceutical residues in cultivation soils and the associated environmental risks, 2) whether pharmaceutical residues are degraded in the soil, and 3) whether sludge-fertilized arable land leaks pharmaceutical residues during rainfall, thereby posing an environmental risk to surrounding water bodies. The study was conducted on fields in Lanna (Lidköping), Igelösa (Lund), and Ultuna (Uppsala), where sewage sludge has been spread for a long period (23, 40, and 65 years respectively). Analyses were performed on sludge, soil samples, and leachate. Initially, a broad spectrum of pharmaceuticals used in Sweden (148 substances) was analysed, followed by those pharmaceutical residues commonly detected in wastewater and sludge in Sweden (up to 35 substances). Soil and sludge were also analysed for metals to identify any correlation between metals and pharmaceutical residues. However, no correlation could be established due to low detection levels of pharmaceutical residues.   Sub-study 1: The results indicate that most pharmaceutical residues in the soils were below detection levels, even though the test fields received sludge quantities up to five times higher than average for Swedish conditions. Trace concentrations of citalopram, oxazepam, propranolol, sertraline, and venlafaxine (1–48 ng/g dry weight) were measured several years after the last sludge application. Triclocarban was found in the highest concentration (160 ng/g dry weight). For most substances, possible accumulation cannot be demonstrated, but it cannot be excluded either. For the same five substances mentioned above (citalopram, sertraline, oxazepam, propranolol, and venlafaxine), accumulation is expected according to the study's theoretical approach. To confirm or exclude accumulation, more sensitive analyses are needed that can measure the expected concentrations in the soil. At the Igelösa field that have been fertilized with sludge at 1ton TS/ha/year since 1981, none of the analyzed pharmaceutical substances could be detected. Yet, triclocarban, an antibacterial chemical that was once common in personal care products and soap, was detected. Thus, it was not possible to confirm accumulation of pharmaceutical residues of therapeutic uses in this field.   Sub-study 2: It was difficult to draw any conclusions regarding the degradation of pharmaceutical residues in the soil, as the mixing of sludge with soil resulted in such significant dilution that all pharmaceutical residues were below detection limits, except for sertraline and citalopram. Citalopram was detected in the soil both before and after sludge application, which may indicate accumulation and makes conclusions regarding degradation challenging. A theoretical calculation using first-order degradation kinetics suggests that ciprofloxacin, ketoconazole, and sertraline degrade in the soil after mixing.   Sub-study 3: During irrigation of sludge-fertilised sand and clay lysimeters, the following substances were detected in the leachate: carbamazepine, citalopram, diclofenac, ibuprofen, metoprolol, and paracetamol. A short period between sludge application and rainfall (1–3 days) caused significant leaching of pharmaceutical residues from both sand and clay lysimeters, while a longer interval between sludge application and rainfall (1 month) did not lead to measurable leaching, except for paracetamol. The mobility of paracetamol and diclofenac was higher in sand than in clay, which could be due to higher adsorption and degradation in clay than in sand. No correlation was observed between the quantity of sludge applied and pharmaceutical residues. Both diclofenac and paracetamol were found in relatively high concentrations in leachate, which may pose an environmental risk to nearby surface and groundwater.Svenskt Vatten Utvecklings anslag till VA-kluster Mälardalen 2019–2022. Projektnummer SVU 18-13

    Modifying the Influence Method for Scintillators using Time-of-Flight tagged Neutrons

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    The Influence Method [1] provides a novel and simple approach to determine detection efficiencies without prior knowledge of the particle flux, but has been shown to produce wrong predictions for scintillators [2]. In this work, the Influence Method is applied to plastic scintillators using fast neutrons with energies between 1.5 MeV and 6.5 MeV from an Am-Be source. The neutrons are time-of-flight tagged so that an energy-dependent efficiency prediction canbe performed. It is investigated if setting a lower detection threshold to simulate neutron removal can improvethe Influence Method predictions. Additionally, an alternative method (the No Influence Method) is developed where the efficiency estimator uses assumptions more appropriate for the interactions of fast neutrons with scintillators. The obtained results for the total detection efficiency, both from the unaltered Influence Method, as well as the new No Influence Method are close to the prediction derived from the hydrogen scattering cross section. The energy-dependent efficiency prediction of the No Influence Method decreases with higher neutron energies, as expected for hydrogen scattering. The experimental part is accompanied by a theoretical model which tries to recreate the Influence Method predictions as closely as possible so that the predictions can be corrected for effects that are not accounted for in the original Influence Method. The model predicts an optimal lower detection threshold of 40% of the incident neutron energy to correct for systematic errors of the Influence Method prediction for plastic scintillators over the Am-Be energy range. This threshold could not yet be verified experimentally because the detectors used are not equivalent enough in detection efficiency and gain. [1] I.J. Rios and R.E. Mayer. Absolute particle flux determination in absence of known detector efficiency. The “Influence Method”. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 775:99–104, 2015. [2] A. Sperduti and M. Cecconello. On the limits of the Influence Method in the determination of the intrinsic efficiency of liquid scintillators. Journal of Instrumentation, 14(06):P06004, jun 2019

    Invited perspective on Research Ethics in Response to “The Right to Read Without Being Read : Research Ethics in the Study of Digital Reading Behaviour”

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    This invited perspective is a response to the position paper “The Right to Read Without Being Read: Research Ethics in the Study of Digital Reading Behaviour”. From the point of view of the researcher behind one of the case studies discussed in the position paper, this paper highlights three perspectives on research ethics: 1) the potential negative effects for individuals of studying book streaming data as in the project design are minimal, and ethics have been discussed continuously in the project; 2) the question whether this kind of data is to be considered sensitive data or not is not simple, and it is important to restrict this label to data that is indeed sensitive; and 3) questions concerning privacy evoked by this kind of reader data are recurrently addressed in the research by the author

    Adapted Support to Families Headed by Parents With Intellectual Disability Through Support to Practitioners : SUF Resource Centre and Examples From Uppsala, Sweden

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    Background Parents with intellectual disability and their children are entitled to adapted support, but practitioners lack knowledge, have scarce access to adapted methods, and work in siloed organisations with limited resources. SUF resource centre was therefore formed, in Region Uppsala, Sweden, to support families headed by parents with intellectual disability through support to the practitioners who support the families. Method SUF has now existed for 20 years and, in this brief report, we describe SUF's organisation and methods: knowledge dissemination, consultations, development and implementation of adapted methods, research, and support of inter-agency cooperation. Results We describe selected results, including research, development projects, and an external review of SUFs' work.Conclusions We reflect on factors that have been important in developing and maintaining adapted support. We emphasise working together with practitioners—grounded in their needs, opportunities and constraints—and to simultaneously address both parents' and children's rights and needs

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