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Nationalism, war and emotions
No full textThis themed section explores the intricate relationship between nationalism, war, and emotions, drawing from a 2023 conference in Copenhagen on these themes. The selected articles engage critically with the transformative dynamics of nationalism in the context of military victories and defeats. Ute Frevert's article introduces the concept of ‘emotional economy,’ elucidating how honour, shame, and humiliation are strategically manipulated to shape national identities and narratives. Morten Nordhagen Ottesen examines the rise and fall of political Scandinavianism, highlighting how fear and existential anxieties shaped the 19th-century Scandinavian nationalist movements, while challenging the myths of ‘Nordic exceptionalism.’ Rasmus Glenthøj proposes a realist theory of nationalism, integrating international relations and political agency into the study of nationalist movements, critiquing the limitations of Gellner's and Hobsbawm's theories. Together, these contributions emphasise the importance of emotions, agency, and historical context in understanding nationalism. They reject state-centric and determinist approaches, advocating for nuanced analyses that recognise nationalism's role in both fostering unity and driving conflict. As contemporary geopolitics echo 19th-century multipolar power dynamics, this section underscores the enduring relevance of nationalism studies in interpreting the emotional and political forces shaping our worl
Rethinking entrepreneurship in causally entangled crises:A poly-crisis perspective
No full textOver the last few years, the world has witnessed the emergence of a poly-crisis era in which overlapping, causally entangled crises, such as pandemics, war, inflation, natural disasters, etc. converge to challenge assumptions of societal stability upon which much of the field's knowledge base has been developed over the last few decades. In this editorial, we propose a poly-crisis perspective to entrepreneurship and compare it with entrepreneurship under both normal times and a single crisis. In doing so, we highlight the need to reexamine the boundary conditions of our models and to propose some questions, constructs, and methods that deserve increased attention in a world where institutional uncertainty is the rule rather than the exception.</p
Recommended Use of Non-Steroidal Anti-Inflammatory Drugs for Pain Treatment Following Primary Total Hip and Knee Arthroplasties in Denmark. A National Survey
No full textBackground: Non-steroidal Anti-inflammatory drugs (NSAIDs) are effective in reducing acute postoperative pain. However, it is currently unknown what type, dosage, and duration of NSAID are used following primary total hip and knee arthroplasties. We aimed to investigate the use of NSAID following total hip and knee arthroplasties in Denmark, describe general postoperative analgesic regimens, and assess clinicians' attitudes towards NSAID treatment. Method: We conducted a web-based survey distributed to local clinicians responsible for total hip and knee arthroplasties in all public Departments of Orthopedic Surgery in Denmark. The survey focused on standard perioperative treatment practices, and in particular the use of NSAIDs. Results: Of the 40 surgeons invited, 98% responded. The majority (37 of 39, 95%) reported NSAIDs as part of standard analgesic regimes after primary total hip and knee arthroplasties. Ibuprofen was the most commonly used NSAID postoperatively (26 of 37, 70%), typically administered at 1200 mg/day (20 of 26, 77%). The median duration of treatment was 8 days (interquartile range (IQR) 6–12) for total hip arthroplasties and 14 days (IQR 10–14) for total knee arthroplasties. However, there were significant variations between hospitals and regions. Multimodal analgesic treatment using paracetamol, NSAIDs, and opioids was the most common analgesia following total hip and knee arthroplasties. Nine of 38 (24%) were concerned regarding daily clinical treatment with NSAID. Conclusion: NSAIDs, especially ibuprofen, are routinely recommended as part of multimodal therapy for postoperative pain after primary total hip and knee arthroplasties in Denmark. The standard dose is 1200 mg/day, with a median treatment duration of 8 days for total hip arthroplasties and 14 days for total knee arthroplasties, though practices vary across different hospitals and regions.</p
“So fast on the keys, when do you have time to meet”:Interactionally generated invitations in Danish Tinder chats
No full textThis paper investigates how Tinder users in Denmark interactionally generate invitations to meet through post-match chats. Based on a collection of 194 Tinder chats collected in 2020, from which 19 examples involving invitations were identified and analyzed using methodology inspired by Conversation Analysis focusing on the strategies used to navigate the delicate process of proposing a meeting.The paper analyzed three ways of generating invitations interactionally: 1) interpreting response time as an indicator of interest, where quick replies are taken as signs of engagement and willingness to meet; 2) basing the invitation on contextually favorable conditions, such as weather or proximity, which are framed as low-effort and convenient for the recipient; and 3) utilizing self-disclosure to propose meeting activities that align with the recipient’s preferences or personal information revealed during the chat.These strategies allow users to test the waters before asking for a meeting, thus minimizing the likelihood of rejection. By treating invitations as collaborative actions, where the recipient’s interest is implied rather than directly solicited, users manage the potential social risks involved in proposing face-to-face interactions. The findings highlight the unique affordances of Tinder as a platform, such as timestamps and geolocation features, which shape the way invitations are constructed and understood. This study contributes to existing research on digital communication by showing how invitations in online dating are interactionally achieved through subtle, recipient-designed strategies that exploit the app’s features while preserving face and mitigating social risks
The Influence of Negative Online Social Support on Entrepreneurship
No full textSocial støtte anerkendes bredt som en vigtig ressource i entreprenørskab, som udveksles gennem netværk for at give følelsesmæssig opmuntring, praktisk hjælp og en følelse af tilhørsforhold. Disse ressourcer bidrager til positive resultater, der hjælper entreprenører med at navigere i usikkerhed, opbygge modstandskraft og forfølge muligheder. Traditionelt har sådan støtte været forankret i offline-interaktioner, hvor ansigt-til-ansigt kommunikation og relationel nærhed former, hvordan støtten udvikler sig og fortolkes. Dog har fremkomsten af online-platforme markant ændret landskabet for entreprenørielle netværk. Onlinefunktioner såsom asynkron kommunikation, bredere rækkevidde og reducerede relationelle begrænsninger gør det muligt for entreprenører at engagere sig i forskellige netværk og få adgang til støtte ud over geografiske og sociale grænser. Disse funktioner har udvidet omfanget af social støtte og giver entreprenører mulighed for at signalere behov, modtage uopfordret feedback og opretholde en bred vifte af kontakter, som de kan aktivere i fremtiden. Dette skift har introduceret nye dynamikker i støtteprocessen og ændret, hvordan entreprenører søger, fortolker og reagerer på ressourceinput.Mens meget af litteraturen om entreprenørskab fremhæver fordelene ved social støtte, skifter denne afhandling fokus til dens negative dimensioner, som stadig er underbelyst, især i online sammenhænge. I modsætning til offline kontekster udvisker online platforme ofte sociale grænser og reducerer ansvarlighed, hvilket tillader individer, herunder fremmede eller ikkenære relationer, at deltage i samtaler uden den store investering i relationen og uden omtanke for konsekvenserne. Disse forhold kan give anledning til negative og forstyrrende interaktioner, såsom trolling eller uopfordret kritik, som kan eskalere og påvirke entreprenørers kognitive bearbejdning og adfærdsmæssige reaktioner.Det er vigtigt at understrege, at denne afhandling ikke ser entreprenører som passive modtagere af støtte, men som aktive agenter, der strategisk engagerer sig i deres netværk. Afhandlingen undersøger, hvordan entreprenører aktivt deltager i online miljøer, strategisk tiltrækker social støtte og reagerer på negative sociale interaktioner, og den fremhæver de konsekvenser, som interaktionerne har for entreprenørernes adfærd og trivsel. Dette agentiske perspektiv udfordrer traditionelle antagelser og understreger den dynamiske karakter af entreprenørielle netværk.Ved at betragte entreprenører som netværksagenter frem for passive modtagere, understreger afhandlingen vigtigheden af at forstå både de betingelser, hvorunder støtte mobiliseres, og de resultater, der følger, når støtten opfattes eller udøves som negativ. Dette perspektiv leder til afhandlingens centrale forskningsspørgsmål:“Hvad er de forudgående faktorer for og konsekvenser af online social støtte i entreprenørskab, særligt når støtten er negativ?” Denne afhandling undersøger først forudsætningerne for social støtte i online og offline kontekster og fremhæver entreprenører som aktive agenter, der strategisk engagerer deres netværk. Den viser, hvordan entreprenører tilpasser sig normer og funktioner i hver kontekst for at mobilisere støtte fra ikke-nære relationer.Dernæst undersøger afhandlingen effekterne af negativ social støtte på entreprenørielle handlinger, med fokus på hvordan destruktiv feedback kognitivt bearbejdes og omsættes til handling. Tillid til muligheden identificeres som en central mediator, og effekten af feedback herpå afhænger af, hvordan den leveres. Bemærkelsesværdigt er det, at negativ støtte ikke altid udløser en umiddelbar negativ reaktion online.Afhandlingen undersøger også, hvordan negativ online social støtte påvirker entreprenørers livstilfredshed. Reaktioner fra fremmede kan forstyrre kognitive processer mere end feedback fra nære relationer, og det fremhæver dermed både de følelsesmæssige omkostninger ved online engagement såsom livstilfredshed, samt betydningen af den relationelle kontekst.Forskningsspørgsmålet besvares gennem kvantitative analyser i tre separate studier, hver baseret på et selvstændigt datasæt. Alle tre artikler i afhandlingen er struktureret omkring testbare hypoteser og anvender statistiske metoder til at undersøge relationer mellem centrale variable. Analyserne inkluderer blandt andet multiple regressionsmodeller og OLS-regression, anvendt til at vurdere både forudsætninger for og konsekvenser af online social støtte i entreprenørielle sammenhænge.Ved at integrere tre dimensioner – netværksmæssige forudsætninger, adfærdsmæssige reaktioner og trivselsmæssige konsekvenser – bidrager denne afhandling til en mere nuanceret forståelse af social støtte i entreprenørskab. Den understreger den kontekstafhængige karakter af social støtte og viser, at social støtte ikke kun formes af relationelle dynamikker, men også af de særlige funktioner i de miljøer, hvori den leveres. Resultaterne giver teoretiske og praktiske indsigter i, hvordan entreprenører navigerer i online miljøer, fortolker negativ social støtte, og hvordan disse fortolkninger former deres efterfølgende entreprenørielle adfærd og trivsel.Denne afhandling bidrager med tre centrale indsigter. For det første defineres entreprenøriel social støtte som en kontekstafhængig og agentisk proces. Entreprenører tilpasser aktivt deres strategier til online og offline kontekster ved at anvende sociale færdigheder og mægleradfærd for at mobilisere støtte baseret på hver konteksts funktioner.For det andet udfordrer afhandlingen antagelsen om, at social støtte er overvejende positiv ved at undersøge dens negative dimensioner online. Destruktiv feedback fra fremmede kan føre til, at idéer revideres frem for at blive opgivet, men en sådan feedback kan også reducere livstilfredsheden på grund af opadgående social sammenligning. Feedback fra nære relationer viser sig at være mindre forstyrrende på grund af tillid og fortrolighed.For det tredje tydeliggør afhandlingen, hvordan entreprenører kognitivt bearbejder negativ online støtte. Tillid til muligheden og opadgående social sammenligning identificeres som centrale mekanismer, der former adfærdsmæssige og følelsesmæssige reaktioner. Selvom feedback i første omgang kan reducere tilliden til muligheden, kan refleksiv bearbejdning føre til konstruktiv omfortolkning og øget selvtillid efter idéen er revideret.Social support is widely recognized as a vital resource in entrepreneurship, where it is exchanged through networks to provide emotional encouragement, practical assistance, and a sense of belonging. These resources contribute to positive outcomes that help entrepreneurs navigate uncertainty, build resilience, and pursue opportunities. Traditionally, such support has been rooted in offline interactions, where face-to-face communication and relational closeness shape the nature and interpretation of support. However, the rise of online platforms has significantly transformed the landscape of entrepreneurial networking. Online affordances, such as asynchronous communication, broader reach, and reduced relational constraints, enable entrepreneurs to engage with diverse networks and access support beyond geographic and social boundaries. These affordances have expanded the scope of social support, allowing entrepreneurs to broadcast their needs, receive unsolicited feedback, and maintain a wide range of contacts for future engagement. This shift has introduced new dynamics into the support process, altering how entrepreneurs seek, interpret, and respond to resource inputs.While much of the entrepreneurship literature emphasizes the benefits of social support, this dissertation shifts focus to its negative dimensions, which remain underexplored, particularly in online settings. Unlike offline contexts, online platforms often blur social boundaries and reduce accountability, allowing individuals—including strangers or non-close relations—to participate in conversations with minimal relational investment or consequences. These conditions can give rise to negative, disruptive interactions such as trolling or unsolicited criticism, which may escalate and influence entrepreneurs’ cognitive processing and behavioral responses.Crucially, this study does not view entrepreneurs as passive recipients of support, but rather as active agents who strategically engage with their networks. It explores how entrepreneurs proactively participate in online environments, strategically elicit social support, and respond to negative social interactions, highlighting their consequences on entrepreneurial behavior and well-being. This agentic perspective challenges traditional assumptions and emphasizes the dynamic nature of entrepreneurial networking.By viewing entrepreneurs as network agents rather than passive recipients, the study emphasizes the importance of understanding both the conditions under which support is mobilized and the outcomes that follow when the support is perceived as negative. This perspective leads to the central research question of the dissertation:“What are the antecedents and outcomes of online social support in entrepreneurship, particularly when the support is negative?” This dissertation first examines the antecedents of social support in both online and offline settings, with a focus on entrepreneurs as active agents who strategically engage with their networks. It highlights how entrepreneurs adapt to the norms and affordances—or allowing functions— of each context to mobilize support from non-close relations.Second, the dissertation explores the effects of negative social support on entrepreneurial behavior, focusing on how destructive feedback is cognitively processed and subsequently acted upon. Opportunity confidence is identified as a key mediator, and the impact of feedback depends on how it is delivered. Notably, negative support does not always trigger an immediate adverse response in online settings.Third, the dissertation investigates how negative online social support affects entrepreneurs’ life satisfaction. It shows that reactions from strangers can disrupt cognitive processes more than those from strong ties, highlighting the costs of online engagement and the importance of relational context.The research question is addressed through quantitative analyses across three distinct studies, each based on a separate dataset. All three papers in the dissertation are structured around testable hypotheses and employ statistical techniques to examine relationships between key variables. Specifically, the analyses include multiple regression models such as ordinary least squares (OLS) regressions and hierarchical regression, ANOVA analysis with LSD post hoc and PROCESS Model 4 which are applied to assess both the antecedents and outcomes of online social support in entrepreneurial contexts.By integrating the three dimensions of networking antecedents, behavioral responses, and wellbeing outcomes, this dissertation contributes a more nuanced understanding of social support in entrepreneurship. It emphasizes the context-sensitive nature of support, showing that its effects are shaped not only by relational dynamics but also by the distinct affordances of the settings in which it is delivered. The findings offer theoretical and practical insights into how entrepreneurs navigate online environments, interpret negative social support, and how these interpretations shape their subsequent entrepreneurial behavior and well-being.This dissertation makes three key contributions. First, it conceptualizes entrepreneurial social support as a context-sensitive and agentic process. Entrepreneurs actively adapt their strategies to online and offline settings, using social skills and brokerage behaviors to mobilize support based on each context’s affordances. Second, it challenges the assumption that social support is inherently positive by examining its negative dimensions in online settings. Destructive feedback from strangers can prompt idea revision rather than abandonment, but upward social comparison in response to such feedback reduces life satisfaction. Notably, negative feedback from strong ties is less disruptive due to trust and familiarity. Third, the dissertation clarifies how entrepreneurs cognitively process negative online support. Opportunity confidence and upward social comparison are identified as key mechanisms shaping behavioral and emotional responses. While feedback may initially lower confidence, reflective processing can lead to constructive reframing and an increase in confidence following subsequent revisions
Impact of tracer uptake rate on quantification accuracy of myocardial blood flow in PET:A simulation study
No full textBackground: Cardiac perfusion PET is commonly used to assess ischemia and cardiovascular risk, which enables quantitative measurements of myocardial blood flow (MBF) through kinetic modeling. However, the estimation of kinetic parameters is challenging due to the noisy nature of short dynamic frames and limited sample data points. Purpose: This work aimed to investigate the errors in MBF estimation in PET through a simulation study and to evaluate different parameter estimation approaches, including a deep learning (DL) method. Materials and Methods: Simulated studies were generated using digital phantoms based on cardiac segmentations from 55 clinical CT images. We employed the irreversible 2-tissue compartmental model and simulated dynamic 13N-ammonia PET scans under both rest and stress conditions (220 cases each). The simulations covered a rest K1 range of 0.6 to 1.2 and a stress K1 range of 1.2 to 3.6 (unit: mL/min/g) in the myocardium. A transformer-based DL model was trained on the simulated dataset to predict parametric images (PIMs) from noisy PET image frames and was validated using 5-fold cross-validation. We compared the DL method with the voxel-wise nonlinear least squares (NLS) fitting applied to the dynamic images, using either Gaussian filter (GF) smoothing (GF-NLS) or a dynamic nonlocal means (DNLM) algorithm for denoising (DNLM-NLS). Two patients with coronary CT angiography (CTA) and fractional flow reserve (FFR) were enrolled to test the feasibility of applying DL models on clinical PET data. Results: The DL method showed clearer image structures with reduced noise compared to the traditional NLS-based methods. In terms of mean absolute relative error (MARE), as the rest K1 values increased from 0.6 to 1.2 mL/min/g, the overall bias in myocardium K1 estimates decreased from approximately 58% to 45% for the NLS-based methods while the DL method showed a reduction in MARE from 42% to 18%. For stress data, as the stress K1 decreased from 3.6 to 1.2 mL/min/g, the MARE increased from 30% to 70% for the GF-NLS method. In contrast, both the DNLM-NLS (average: 42%) and the DL methods (average: 20%) demonstrated significantly smaller MARE changes as stress K1 varied. Regarding the regional mean bias (±standard deviation), the GF-NLS method had a bias of 6.30% (±8.35%) of rest K1, compared to 1.10% (±8.21%) for DNLM-NLS and 6.28% (±14.05%) for the DL method. For the stress K1, the GF-NLS showed a mean bias of 10.72% (±9.34%) compared to 1.69% (±8.82%) for DNLM-NLS and −10.55% (±9.81%) for the DL method. Significance: This study showed that an increase in the tracer uptake rate (K1) corresponded to improved accuracy and precision in MBF quantification, whereas lower tracer uptake resulted in higher noise in dynamic PET and poorer parameter estimates. Utilizing denoising techniques or DL approaches can mitigate noise-induced bias in PET parametric imaging.</p
Forms of theorising in entrepreneurship – The case of effectuation as a theory
No full textAs of today, the research field of entrepreneurship has developed into its own research community and needs to further develop its specific theorising to account for the distinctiveness of entrepreneurship. This becomes particularly evident with the emergence of effectuation, which is promoted as the first “homegrown” theory of entrepreneurship. The discourse on effectuation as a theory presents an interesting example which shows the challenges of discussing theory due to the different understandings of theory in entrepreneurship research. In this essay, we propose instead to examine the forms of theorising that entrepreneurship scholars engage in. Analysing 42 articles from the discourse on effectuation as a case of entrepreneurship theory, we show which forms of theorising are more prevalent than others, and which forms might be underexplored and could offer potential for future research. While we can and should continue to build on the knowledge about theory from other fields, this essay is an invitation to entrepreneurship scholars to take a step back and reflect on our own theorising in the field. With the three recommendations presented, we aim to provide a starting point for scholars to embrace the plurality of possible forms of theorising in entrepreneurship.</p
Serverless Computing in Cloud-Edge Scenarios
No full textDenne afhandling undersøger udvidelser til serverless computing, med fokus på Function-as a-Service (FaaS), ved at udvide anvendelsesområdet ud over rent offentlige, cloudbaserede arkitekturer til edge-systemer og hybride cloud-edge-implementeringer. Inkluderingen af disse miljøer medfører flere fordele, såsom reduktion af behovet for datatransmission og oprettelsen af et cloud-edge-continuum, således at arbejdsbelastninger kan flyttes på en transparent måde. Understøttelse af disse miljøer skaber også mulighed, for at integrere Internet of Things (IoT)-enheder på en sikker og transparent måde.Inkorporering af edge-systemer medfører imidlertid nye udfordringer, der stammer fra heterogene netværkstopologier og enheder med begrænsede ressourcer. For at imødegå disse udfordringer introducerer dette arbejde flere nye planlægningsmetoder, der udtrykkes gennem udvidelser af APP (Application Priority Policies), et konfigurationssprog for FaaS-schedulers. Disse udvidelser, dvs. topology-aware APP (tAPP), affinity-aware APP (aAPP) og cost-aware APP (cAPP), forbedrer henholdsvis schedulers ved at fokusere på den geografiske fordeling af senheder, affiniteten mellem funktioner og minimering af den forventede ventetid ved kommunikation med eksterne tjenester.Med samme formål præsenterer afhandlingen også FunLess, en open-source serverless platform, der er rettet mod edge- og cloud-edge-implementeringer. Platformen bruger WebAssemblytil at eksekvere funktioner og udnytter dens cross-platform natur og de små binære filestørelser til bedre at målrette enheder med begrænsede ressourcer.Endelig undersøger arbejdet et anvendelsesscenarie, hvor droner fungerer som mobile beregningsenheder inden for platformen. Dette system demonstrerer udførelse og aflastning af opgaver i realtid under upålidelige og mobile netværksforhold, valideret gennem en simuleret katastrofesituation.This thesis investigates extensions to serverless computing, and specifically Function-as-a-Service (FaaS), by broadening its scope beyond purely public, cloud-based architectures, towards edge systems and hybrid cloud-edge deployments. The inclusion of such environments brings several benefits, such as the reduction of data transmission needs and the creation of a cloud-edge continuum across which workloads can be transparently moved. Supporting these environments also creates the possibility to integrate Internet of Things(IoT) devices in a secure, transparent way.Incorporating edge systems, however, brings new challenges stemming from heterogeneous network topologies and resource-constrained devices. To address these, this work introduces several novel scheduling approaches, expressed through extensions of APP(Application Priority Policies), a configuration language for FaaS schedulers. These extensions, i.e., topology-aware APP (tAPP), affinity-aware APP (aAPP), and cost-aware APP(cAPP), respectively improve schedulers by focusing on the geographical distribution ofworkers, the affinity between functions, and the minimisation of the expected latency when communicating with external services.To the same end, the thesis also presents FunLess, an open-source serverless platform geared towards edge and cloud-edge deployments. The platform makes use of WebAssembly for function execution, leveraging its cross-architecture nature and the small size of its binaries to better target resource-constrained devices.Finally, the work explores an application scenario where drones act as mobile computational nodes within the platform. This system demonstrates real-time task execution and offloading in unreliable and mobile network conditions, validated through a simulated emergency response use case
Biomarkers of connective tissue turnover in inflammatory bowel disease - diagnostic and predictive capacity
No full textKronisk inflammatorisk sygdom (CID), inklusiv inflammatorisk tarmsygdom (IBD), består af idiopatiske, prævalente og potentielt invaliderende sygdomme. Omend heterogene, udtrykker de ligheder i symptomatologi herunder fluktuerende sygdomsmønster og overlappende komorbiditet. I behandlingen af disse sygdomme ordineres der overvejende biologisk medicin rettet mod den pro-inflammatoriske tumornekrosefaktor (TNF). Med den nuværende medicinske tilgang opnår en betydelig del af patienterne (op til 60%) intet eller et utilstrækkeligt klinisk behandlingsrespons, hvilket understreger manglen på adækvat behandling. Med et livslangt perspektiv og en forventet stigende sygdomsbyrde udgør CID uundgåeligt en betydelig socio-økonomisk byrde. Fokuseres der på nuværende presserende kliniske udfordringer i behandlingen af IBD, skiller følgende sig ud: tidlig diagnose og rettidig og adækvat medicinsk behandling. At stille en tidlig diagnose kan være en klinisk udfordring på grund af fraværet af en guldstandard (ideal reference) og grundet en forholdsvis stor afhængighed af endoskopiske procedurer. Forsinket diagnose og suboptimal behandling kan have negativ indvirkning på sygdomsprogression (irreversibel organskade), rettidig terapeutisk behandling og i sidste ende livskvaliteten for patienter og pårørende.Kronisk inflammation er bl.a. kendetegnet ved overdreven ekstracellulær matrix (ECM) remodellering og forstyrret bindevævsomsætning. ECM biomarkører som afspejler inflammation, bindevævsomsætning og fibrose/fibrogenese har tidligere udvist diagnostisk og prædiktiv værdi. Således var det sandsynligt, at disse ECM biomarkører, som afspejler patologiske processer, havde potentiale som kliniske værktøjer i IBD diagnose, prognose og prædiktion af behandlingsrespons. Denne afhandling var baseret på planlægning, koordinering og gennemførelse af det observationelle NORDTREAT kohorte studie (bestående af et tværsnitsstudie og et longitudinelt studie) i et nordisk samarbejde med prospektiv inklusion af patienter i Danmark, Sverige, Norge og Island. En protokolartikel, der præsenterer studiedesign, metodologi, statistik, samt primære- og sekundære udfaldsmål, blev offentliggjort som en del af denne afhandling. Tværsnitsstudiet i NORDTREAT og BELIEVE kohortestudiet udgjorde grundlaget for de serologiske målinger og studier af ECM biomarkører i de præsenterede kliniske udfordringer indenfor IBD behandling. NORDTREAT tværsnitsstudiet omfattede 241 voksne patienter, som blev henvist til en gastroenterologisk afdeling på mistanke om IBD (symptomatiske og behandlingsnaive, dvs. en klinisk relevante situation). Patienterne fik taget blodprøver ved baseline og blev efterfølgende diagnosticeret med Crohns sygdom (CD), colitis ulcerosa (UC), IBD-uklassificeret (IBD-U) eller inkluderet som symptomatiske kontroller. ELISA-målinger blev udført for at vurdere niveauerne af ECM biomarkører for vævsfibrose: henholdsvis CTX-III, PRO-C4, PROC5 og PRO-C16, inflammation (VICM) og slimhindeskader (C3M, C4M, C6M). Det primære formål med NORDTREAT tværsnitsstudiet var at udforske den kliniske værdi af et panel af ECM biomarkører til diagnosticering af IBD (CD, UC, IBD-U) versus symptomatiske kontroller i forbindelse med første kliniske besøg af patienter henvist på mistanke om IBD. Den logistiske prædiktionsmodel, som opnåede den bedste sondring mellem patienter med IBD versus symptomatiske kontroller omfattede CTXIII og C6M (AUC 0,64, 95 % CI 0,56 - 0,70). En efterfølgende post-hoc analyse af modellens anvendelighed i forhold til differentiering af patienter med kolon CD fra patienter diagnosticeret med UC inkluderede biomarkørerne VICM, C4M, PRO-C5 og PRO-C16. Denne prædiktive regressionsmodel gav en AUC på 0,80 (95 % CI 0,69 - 0,98).Det prospektive kohortestudie BELIEVE (afsluttet i 2020) inkluderede 233 patienter diagnosticeret med CID inklusiv CD, UC, reumatoid arthritis (RA), aksial spondyloarthritis (axSpA), psoriasisarthritis (PsA) og psoriasis (PsO). Voksne patienter med CID, som påbegyndte eller skiftede (efter fejlslagen antiTNF behandling) biologisk behandling, var studieberettigede. Der blev indsamlet blodprøver ved baseline samt efter 14-16 ugers biologisk behandling, og niveauerne af atten ECM biomarkører blev målt i ELISA-undersøgelser. Det primære formål med BELIEVE studiet var at udforske den kliniske værdi af ECM biomarkører som prædiktorer for biologisk behandlingsrespons i en population af patienter med CID. Sygdomsspecifik biologisk behandlingsrespons blev opnået hos 54% af studiepopulationen med CID (fra 44% til 65% i subgrupperne af CID). Anvendeligheden af de enkelte ECM biomarkører til prædiktion af sygdomsspecifik behandlingsrespons blev vurderet ved måling af AUC (værdier fra 0,47 til 0,59). En eksplorativ analyse (PCA) afslørede en gruppering af ECM biomarkørerne i fem undergrupper/komponenter. Vi fandt imidlertid ikke signifikant sammenhæng mellem nogen af de fem komponenter og klinisk behandlingsrespons i den efterfølgende logistiske regressionsanalyse. Konklusionen i denne Ph.d.-afhandling er, at NORDTREAT tværsnitsstudiet dokumenterede, at hverken de enkelte kandidatbiomarkører eller en profil af biomarkører havde tilstrækkelig diagnostisk værdi (foruddefineret nedre grænse for AUC på 0,80). Dette på trods af anvendelsen af et panel af tidligere og grundigt undersøgte ECM biomarkører. Imidlertid afslørede en posthoc analyse en prædiktionsmodel, som med succes kunne skelne patienter med kolon CD fra patienter med UC. BELIEVE studiet dokumenterede, at selvom patienter med CID har adskillige fællestræk, og det anvendte ECM biomarkørpanel var grundigt evalueret, lykkedes det ikke, at påvise nogen enkelt ECM biomarkør eller biomarkørprofil, som kunne prædiktere biologisk behandlingsrespons.Med udsigt til kraftigt stigende CID prævalens er efterspørgslen på valide kliniske værktøjer, som muliggør tidlig diagnose, prognose og pålidelig prædiktion af klinisk behandlingsrespons, så relevant som nogensinde. For at afbøde de uundgåelige konsekvenser af kronisk inflammation, øge livskvaliteten for patienter og minimere forbruget af sundhedsressourcer (f.eks. anvendt på hospitalsindlæggelser, endoskopiske procedurer og overdreven medicinering), er omkostningseffektive og minimalt invasive kliniske værktøjer til differentiering af umiddelbart ens, men væsentligt forskellige sygdomme, og iværksættelse af hurtig og effektiv terapeutisk intervention af enorm stor betydning.Chronic inflammatory disease (CID) including inflammatory bowel disease (IBD) constitute idiopathic, prevalent and potentially debilitating diseases. Albeit heterogeneity, they express similarities in symptomatology e.g., fluctuating disease pattern and overlapping co-morbidity. Biological medications targeting the proinflammatory tumor necrosis factor (TNF) are predominantly prescribed. Currently, a significant part of patients (up to 60%) has no or insufficient clinical treatment response, pinpointing the lack of adequate management. With a lifelong perspective and an overall increasing disease burden, CID inevitably constitutes a significant socio-economic burden. If focusing on present clinical challenges in IBD management, early diagnosis and timely and adequate therapeutic treatment stand out. Early diagnosis may pose a clinical challenge, due to the absence of a golden standard, and relative dependency on endoscopic procedures. Delayed diagnosis and suboptimal treatment may negatively affect disease progression (irreversible organ damage), timely therapeutic management and ultimately quality of life for patients and relatives.A hallmark of chronic inflammation is excessive extracellular matrix (ECM) remodeling and disturbed connective tissue turnover. Biomarkers of the ECM mirroring inflammation, connective tissue turnover, and fibrosis/fibrogenesis have previously demonstrated diagnostic and predictive utility. Therefore, it was plausible that these biomarkers of ECM reflecting pathological processes had potential as clinical tools for aiding IBD diagnosis, prognosis, and prediction of treatment response. This thesis was based upon the planning, coordination and conduction of the observational NORDTREAT cohort study (consisting of a cross-sectional study and a longitudinal study) partnering in a Nordic collaboration with prospective enrolment of patients in Denmark, Sweden, Norway and Iceland. A protocol article highlighting details of study design, methodology, statistics, primary and secondary outcomes was published, as part of this thesis. The NORDTREAT cross-sectional study and the BELIEVE cohort study constituted the foundation of the serological investigations of ECM biomarkers in the two clinical challenges within IBD management presented above. The NORDTREAT cross-sectional study enrolled 241 adult patients referred on suspicion of IBD (symptomatic and treatment naïve i.e., clinical relevant setting). Patients had blood samples taken at baseline, and were subsequently diagnosed with either Crohn’s disease (CD), ulcerative colitis (UC), IBDunclassified (IBD-U) or symptomatic controls. ELISA was conducted to assess levels of biomarkers of tissue fibrosis: CTX-III, PRO-C4, PRO-C5, and PRO-C16, immune cell activity (VICM), and mucosal damage (C3M, C4M, C6M), respectively. The primary aim of the NORDTREAT cross-sectional study was to explore the utility of a panel of ECM biomarkers on diagnosis of IBD (CD, UC, IBD-U) versus symptomatic controls at first clinical visit in patients referred to a gastroenterology department with suspected IBD. The logistic prediction model achieving the best distinction of patients with IBD versus symptomatic controls included CTXIII and C6M (AUC 0.64, 95% CI 0.56 - 0.70). Subsequent post-hoc analysis of the discriminative utility of the model to separate patients with colonic CD from patients diagnosed with UC included the biomarkers VICM, C4M, PRO-C5, and PRO-C16. This predictive model provided an AUC of 0.80 (95% CI 0.69 - 0.98).The BELIEVE cohort study (finalized in 2020) prospectively enrolled 233 patients with CID including CD, UC, rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and psoriasis (PsO). Adult patients initiating or switching (after anti-TNF failure) biological therapy were eligible for participation. Blood samples were collected at baseline and 14-16 weeks after initiating biological therapy, and levels of eighteen ECM biomarkers were measured by ELISA. The primary aim of the BELIEVE study was to explore the clinical utility of ECM biomarkers as predictors of biological treatment response in a population of patients with CID. Disease-specific biological treatment response was achieved in 54% of the study population with CID (ranging from 44% to 65% in the subgroups of CID). The utility of the single ECM biomarkers for prediction of disease specific treatment response was addressed by measuring the AUC (values ranging from 0.47 to 0.59). An explorative principal component analysis was conducted and revealed a clustering of the ECM biomarkers in five groups/components. However, the logistic regression analysis did not demonstrate any significant association between the five components retrieved and clinical treatment response. In conclusion, the NORDTREAT study documented, that even though exploring previously applied and thoroughly investigated ECM biomarkers, neither of the single candidate biomarkers nor profile of biomarkers had sufficient diagnostic utility (predefined lower limit of AUC of 0.80). However, post hoc analysis revealed a prediction model successfully discriminating patients with colonic CD from patients with UC. The BELIEVE study documented, that despite of multiple common features in patients with CID and application of an intensively assessed ECM biomarker panel, we did not succeed retrieving any single ECM biomarker nor biomarker profile predictive of biological treatment response.With future prospects of sharply increasing prevalence of CIDs the search for valid clinical tools enabling early diagnosis, prognosis of disease course and reliable prediction of treatment response is as relevant as ever. To mitigate the inevitable consequences of chronic inflammation, increase the quality of live for patients, and minimize scarce health care resources (e.g., spent on hospitalizations, endoscopic procedures and excessive medication), cost-efficient and minimally invasive clinical measures to distinguish similar but essentially different diseases, and enabling prompt and efficient therapeutic intervention is of immense importance.<br/
Psychological predictors of mental well-being in Judo athletes: Exploring the impacts of the coach-athlete relationship, social support, and psychological safety
No full textPsychological predictors of mental well-being are crucial for improving athletes' mental health. Identifying and supporting the mental health of athletes is essential for a well-functional elite sports system. Previous research suggested that the quality of the coach-athlete relationship and a psychologically safe interpersonal environment can positively influence mental health. However, the interplay between these components and the role of social support has yet to be tested empirically. Therefore, the present study explored the impact of coach-athlete relationship quality and psychological safety on mental well-being through perceived social support within and outside sports. A sample of 323 national and international Turkish Judo athletes completed online questionnaires. Structural equation modelling revealed significant positive effects of the coach-athlete relationship on Judo athletes' mental well-being, mediated by social support and psychological safety. These findings demonstrate that the quality of the coach-athlete relationship can enhance perceived support in and outside sport, and perceived social support can contribute to experiencing a psychologically safe environment within which mental health issues are discussed, leading to an elevated well-being. The coach-athlete relationship alone was not a key factor for enhancing a psychologically safe environment related to athletes' mental health. However, the relationship athletes develop with their coach positively influences mental well-being via the perception of received social support and an enhanced psychologically safe environment specifically designed to allow athletes to discuss mental health issues. These results offer practical recommendations for coaches and professionals working in sports to improve athletes’ mental well-being