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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Alving, Berit Elisabeth; Haastrup, Mette Fentz;

    Indeholder moduler opdelt i temaer, som indeholder links, videoer og tekstuddrag, samt oplæg til refleksion og diskussion. Anvendes internt for partnere under Et Sundere Syddanmark - Gymnasiepanelet.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Lüchau, Elle Christine;
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Jespersen, Christian;

    Afhandlingen analyserer i hvilket omfang Traktatfrihederne forpligter medlemsstaterne til at yde kompensation for underskud til koncerner og til selskaber med faste driftssteder. Afhandlingen er inddelt i otte kapitler. Afhandlingens kapitel 1 præsenterer emnet, problemformulering samt metode.Afhandlingens kapitel 2 introducerer emnet på medlemsstabsniveau. Dette kapitelintroducerer de udfordringer, som - på den ene side - den asymmetriske behandling af overskud og underskud og - på den anden side - de grundlæggende principper for beskatning skaber i relation til fradrag, som skaber et underskud. Herudover beskriver kapitlet de mest almindelige metoder, som anvendes for at yde underskudskompensation. Endelige beskriver kapitlet de udfordringer, som opstår i relation til underskudskompensation, når selskaber og koncerner udøver grænseoverskridende virksomhed. Afhandlingens kapitel 3-5 introducerer de fire friheder og redegør for, hvordan EU domstolen vurderer, om en national skattelovgivning er i uoverensstemmelse med en traktatfrihed. Kapitel 3 introducerer de fire traktatfriheder og redegør for traktatfrihedernes restriktionsbegreb, som dette fortolkes i relation til nationale regler på området for direkte beskatning. På grundlag af dette indledende kapitel uddyber kapitel 4 restriktionstesten, som består af henholdsvis ulempetesten of sammenlignelighedstesten, mens kapitel 5 uddyber justifikationstesten.Afhandlingens kapitel 6-7 analyserer EU-domstolens praksis vedrørende underskudskompensation. Kapitel 6 analyserer i hvilket omfang en medlemsstat er forpligtet til at yde kompensation for underskud lidt af koncerner i grænseoverskridende situationer. Dette afsnit analyserer således EU-domstolens praksis vedrørende horisontalekompensationsordninger samt underskudsanvendelse i forlængelse af en fusion. Kapitel 7 analyserer i hvilket omfang en medlemsstat er forpligtet til at yder kompensation for underskud lidt af et selskab med et fast driftssted. Dette afsnit analyserer EU-domstolens praksis vedrørende fradrag for underskud i det underskudsgivende indkomstår, fradrag for underskud i medfør af vertikale kompensationsordninger, genbeskatning af underskud som allerede er taget i betragtning og udskydelse af beskatning som følge af underskud. The thesis analyses to what extent the Treaty freedoms require the EU Member State to provide loss compensation to corporate groups and to companies with permanent establishments in the European Union. The thesis is divided into eight chapters. The first part of the thesis presents the subject, the research questions, the motivation for the choice of subject, delimitation and legal philosophy and methods.Chapter 2 introduces the subject on Member State-level. This chapter introduces the challenges that are caused by - on the one hand - the asymmetrical treatment of profits and loss and - on the other hand - the fundamental principles of taxation in respect of losses. This chapter further introduces the most common methods adopted in order to provide loss compensation. Finally, the chapter elaborates on the challenges that arise in relation to loss compensation when corporate groups and companies exercise cross-border activity.Chapter 3-5 introduces the four Treaty freedoms and explain how the European Court of justice examines whether a nation legislation on direct taxation violates a Treaty freedom. Chapter 3 introduces the four Treaty freedoms and explains how the European Court of Justice interprets the concept of restriction in respect of national legislation on direct taxation. On that basis, chapter 4 elaborates on the restriction test, which comprises the disadvantage test and the comparability test, while chapter 5 elaborates on the justification test.Chapters 6-7 analyses the case law of the European Court of Justice on loss compensation. Chapter 6 analyses to what extent the Treaty freedoms require a Member State to provide loss compensation to corporate groups in cross-border situations. This chapter analyses the case law on horizontal loss compensation schemes and national provisions providing for loss compensation in the context of a merger. Chapter 7 analyses to what extent a Member State is required to provide loss compensation to a company with a permanent establishment. This chapter analyses the case law concerning deductions of losses during the loss-making income year, deduction of losses by means of horizontal loss compensation schemes, reincorporation of losses previously deduction and the deferral of taxation as a consequence of losses.Chapter 8 contains the conclusion on the thesis. This chapter concludes to what extent the Treaty freedoms require the Member States to provide loss compensation to corporate groups in cross-border situations and to a company with a permanent establishment.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Thøgersen, Dagfinn Mørkrid;

    Conduct problems in adolescence is a well-known phenomenon where a range of negative behaviors can have multiple detrimental effects on the youth themselves, their family members and surroundings. Callous-unemotional (CU) traits have been linked to more severe and persistent antisocial behaviors and are characterized by a lack of empathy, a lack of remorse and guilt, a lack of concern in performance and shallow affect (Frick et al., 2014). Research suggests that there might be a distinct developmental pathway for conduct problems in children with CU traits, evidenced by both neurobiological and -psychological indicators (Frick et al., 2014). This has warranted the addition of the CU-specifier “with limited prosocial emotions” to the conduct disorder. CU traits might thereby provide a more nuanced assessment of risk factors associated with conduct problems and could assist in providing more optimal treatments for youth with these characteristics.This PhD-dissertation had three aims related to CU traits in adolescents. The first aim was to assess the construct validity of a commonly used measure of CU traits, the Inventory of CallousUnemotional traits (ICU), in a Norwegian sample of at-risk adolescents. The second aim was to assess the degree to which CU traits are linked to treatment outcomes among adolescents with behavior problems who receive Functional Family Therapy (FFT). The third aim was to assess the degree of change in CU traits for adolescents participating in FFT. The analyses were based on data from a single group pre-post evaluation of FFT in Denmark (N=407), and a randomized controlled trial of FFT in Norway (N=159-160). Aim 1: The construct validity of the Norwegian translation of the ICU. Previous research is somewhat inconsistent regarding the factorial structure of the ICU and the items on the Unemotional subscale have been particularly scrutinized. The first paper included in this thesis (Paper 1) thus studied the construct validity of the Norwegian translation of the ICU. A multi-informant sample of 160 adolescents and their parents and teachers provided the data for this study. The results from Paper 1 showed that a two-factor solution of a Callousness factor and an Uncaring factor provided the best fit to the model across respondent groups. The Callousness factor was most strongly related to anti-social behavior, while the Uncaring factor was most strongly related to the lack of fear. Despite these distinct correlational patterns, the two-factor structure could be the result of a common method-variance effects related to whether items were standard- or reverse-scored. It is therefore likely that CU traits are best operationalized as a unidimensional measure. Aim 2: The relationship between CU traits and treatment outcomes. The degree to which CU traits impact treatment outcomes for adolescents with behavior problems was the focus of the remaining papers of this thesis (Paper 2 and Paper 3). In both of these there was little evidence to suggest that CU traits were linked to diminished treatment outcomes. On the contrary, CU traits were linked to steeper decreases in anti-social behavior and steeper increases in prosocial behavior in Paper 2. In Paper 3, the relationships between CU traits and treatment outcomes became non-significant when controlling for baseline levels of behavior problems. One possible explanation for these findings is that adolescents with CU traits have more problems at baseline and thereby a greater potential range of improvement. Importantly, the results in Paper 3 showed that although CU traits were either neutrally or positively related to treatment outcomes, baseline CU traits were still predictive of problematic behavior at the end of treatment. This suggests that adolescents with elevated levels of CU traits could be in need of more tailored and long-term services to sustain behavioral improvements over time. The impact of CU traits on treatment outcomes was not different when comparing FFT treatment to an active control condition, when only looking at those with clinical levels of externalizing problems at the start of treatment or when comparing primary to secondary CU subtypologies.Aim 3: The malleability of CU traits. With respect to whether CU traits change over the course of treatment, the results from Paper 2 and Paper 3 were somewhat mixed. In both papers the overall change in CU traits across treatment was small, and a reliable decline in CU traits was observed in relatively few adolescents. At the same time, both papers found more pronounced reductions in CU with respect to both magnitude and the proportion of participants with reliable decreases in CU traits among the subset of adolescents with increased CU traits at baseline. This suggests that CU traits could act as a moderator of the malleability of CU traits. There were no differences in the malleability of CU traits when comparing FFT treatment to an active control condition and when comparing primary to secondary CU sub-typologies.Conclusion: The results from this PhD-dissertation point to the need for continued development of measures of CU traits in both research and clinical settings. Furthermore, the results suggest that adolescents with behavior problems and CU traits do benefit from evidence-based and high-quality treatment, through observed declines in aggressive and rule breaking behavior as well as increases in social skills. Such behavioral improvements seem obtainable without a reduction in the CU traits themselves, as the results indicate that CU traits seem to be relatively stable across time even in the context of treatment. Future work should study the possible benefits of prolonged interventions that specifically target CU-associated risk factors in adolescents, to see if behavioral improvements beyond those obtainable in evidence-based programs and high-quality treatments can be reached. The way in which a reduction in CU traits can be achieved and lead to long-term positive outcomes is also of great importance.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Stærk, Kristian;

    Blærebetændelse er en hyppig infektionssygdom i Danmark og rammer personer i alle aldersgrupper. Selvom blærebetændelse let kan behandles med antibiotika vil sygdommen ofte vende tilbage og vi ved ikke meget om hvorfor nogle personer, som er ellers sunde og raske, bliver ramt og ikke andre. På hospitalerne er blærebetændelse også den hyppigste hospitals-erhvervet infektionssygdom som i høj grad kan tilskrives det store forbrug af urinvejskatetre. Blærebetændelse udgør således et stort problem både i samfundet og på hospitalerne.Målet med dette ph.d.-projekt var at udvikle og optimere en blærebetændelse-model i grise og karakterisere infektionsforløbet og patogenesen i dette dyr mhp. at afdække grisens muligheder som translationel dyremodel inden for denne sygdom.I modellen anvendtes konventionelle hun-grise (Landrace x Yorkshire) på ca. 40 kg. Infektionen blev induceret via transurethral inokulation (via blærekateter) med uropatogene E. coli (UPEC). Grisene blev inokuleret med aftagende mængder bakterier for at identificere det mindste nødvendige inokulum og derved karakterisere grisensfølsom over for blærebetændelse. Ved at bruge en ΔFimH mutant blev betydningen af type-1 fimbriae undersøgt. Tilstedeværelsen af intracellulære bakterier blev undersøgt ved at behandle (med antibiotika) inficerede griseblærer ex vivo eller in vivo og herefter mikroskopere med konfokal laser scanning mikroskopi samt ved udpladning af homogeniseret blærevæv. Grisemodellen blev også tilpasset til at facilitere et studie med et nyt antimikrobielt blærekateter.Resultaterne er sammenskrevet i 5 manuskripter (3 publikationer og 2 manuskripter under fagfællebedømmelse) og viser at grise er meget følsomme for UVI og at kun ganske få bakterier er tilstrækkeligt til at give ophav til blærebetændelse. infektionspotentialet er meget afhængigt at type-1 fimbriae, da ΔFimH mutanten var betydeligt svækket. Intracellulære bakterier kunne ikke påvises I blærevæv. I katetermodellen var det antimikrobielle kateter I stand til at forhindre infektion i alle grise til sammenligning med kontrol grise som alle udviklede blærebetændelse.Konklusionen er, at blærebetændelses-modellen i grise er en pålidelig model som afspejler mange vigtige parametre ved human infektion. Derfor er grisen velegnet til patogenese-studier og som præ-klinisk model til at validerer nye behandlinger mod blærebetændelse. Herudover viser studierne at der er betydeligeforskelle i patogenesen, særligt i forhold til den intracellulære kolonisering, mellem mus og grise og indikerer herved at resultater fra mus ikke altid kan ekstrapoleres direkte til større dyr. Urinary tract infection (UTI), in particular cystitis, is a widespread disease in Denmark and the whole world and occurs in all age groups [1]. UTIs constitutes the most common nosocomial infection, the most common cause of sepsis and accounts for approximately 3000 deaths every year in Denmark alone [3, 133]. Community-acquired UTIs are characterized by a high frequency of recurrence, even in otherwise healthy women with no apparent risk factors [1].A part from epidemiological data, much of what we know about the pathogenesis of UTI comes from experimental studies in cell-culture based assays and murine models of cystitis. In these models, uropathogenic Escherichia coli (UPEC), the most common etiological agent of UTI, has been shown to invade bladder epithelial cells forming intracellular dormant reservoir [134]. In mice, these reservoirs can survive antibiotic treatment and seed re-infections [121]. The intracellular pathogenic cascade has been suggested as a plausible explanation to recurrent UTIs in humans as well. However, despite being extensively demonstrated in mice through the last 20 years, only very few studies has indicated a similar pathogenesis in humans and the hypothesis have struggled to become accepted in clinical societies [134-137]. This may in part be explained by an increasing skepticism towards the translatability of murine models to human disease [4].To bridge the gap between mice and humans, this Ph.D project aimed to investigate UPEC pathogenesis, including the intracellular pathogenic cascade, in a new large animal model of UTI in pigs. Pigs have been highlighted as excellent models of infectious diseases and share more similarities to humans in terms of genetics, immune physiology and urinary tract anatomy compared to their rodent counterpart [7]. Female domestic pigs (Landrace x Yorkshire, mix) of roughly 40 kg were used here. The pigs were inoculated through a urinary catheter with UPEC to induce cystitis. Pigs were inoculated with varying concentrations of bacteria to determine minimal infectious inoculum, i.e. the susceptibility to infection. Furthermore, by using a mutant lacking the T1F, one of the most well-described virulence factors of UPEC, the influence of thisfimbriae on infectious outcome was assessed in the porcine model. To investigate the intracellular pathogenic cascade, whole-bladders from infected pigs were investigated for the presence of intracellular bacteria following ex vivo and in vivo antibiotic treatment by analyzing splayed bladders with confocal laser scanning microscopy and plating homogenized tissue samples. Lastly, the model was adapted to facilitate studies of catheter-associated UTI (CAUTI), and with this, an efficacy study of a novel antimicrobial catheter was performed. The results are consolidated in 5 manuscripts (3 published papers, 2 in peer-review) and show that pigs are highly susceptible to UTI, with only a few single bacteria of UPEC capable of successfully infecting this animal. This infectious potential is largely dependent on T1F, as the T1F-deficient mutant was strongly attenuated. Surprisingly, we found no evidence of intracellular persistence upon antibiotic treatment. In the CAUTImodel, we demonstrate proof-of-concept of an antimicrobial bladder catheter that effectively prevented CAUTI in all pigs.In conclusion, the pig represents a robust model that recapitulates important aspects of human UTI. Thereby, the model is appropriate for studies of UTI pathogenesis as well as pre-clinical efficacy studies of new therapeutic treatments or interventions against UTI. Furthermore, the results of these studies show important differences in UTI pathogenesis between mice and pigs, particular in relation to intracellular persistence and thereby support that results from experiments in mice should be interpreted with caution.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Bøgelund Pedersen, Morten; Esmann Fonvig, Christina; Aagaard, Per; Hansen, Gunhild Mo; +2 Authors
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Mai Nielsen, Sabrina;

    Kontekstuelle faktorer (Eng. contextual factors) er vigtige for at få en dybere forståelse af resultaterne fra kliniske forsøg. Gennem det globale Outcome Measures in Rheumatology (OMERACT)-initiativ er der et presserende behov for vejledning i at identificere kontekstuelle faktorer, når der udvikles såkaldte core outcome sets (dvs. et minimum set af målinger der skal foretages i kliniske forsøg). Dette førte til dannelsen af OMERACT-arbejdsgruppen, Contextual Factors Working Group.1. Først præciserede vi det overordnede formål for arbejdsgruppen og udviklede en forskningsplan (artikel I). Hovedformålet var at udvikle en operationel definition og vejledning i at håndtere kontekstuelle faktorer i forsøg indenfor reumatologi, når der udvikles core outcome sets. Derudover ønskede vi at udvikle et generisk sæt af vigtige kontekstuelle faktorer for reumatologiske forsøg.2. Vi undersøgte forskellige forståelser af begrebet kontekstuelle faktorer (artikel II). Ved hjælp af semistrukturerede interviews med 12 forskere/klinikere og 7 patienter, samt kvalitativ indholdsanalyse af interviewdataene, fandt vi to overordnede temaer, der tilsammen beskriver fire forskellige typer af kontekstuelle faktorer, hvoraf tre var relevante indenfor OMERACT.3. Vi udviklede en operationel definition af kontekstuelle faktorer (artikel III). Beskrivelserne for de tre typer blev finpudset, og vi gennemførte et Delphi-studie med 33 patienter og 128 klinikere/øvrige. Efter to Delphi-runder var der opnået konsensus. De tre faktortyper blev kaldt effect modifying -, outcome influencing - og measurement affecting contextual factors, som på dansk kan formidles som hhv. effekt-modificerende -, udfalds-influerende og målings-påvirkende kontekstuelle faktorer.4. Vi undersøgte en række patientkarakteristika for, om de kunne ændre behandlingseffekten på tværs af forsøg indenfor reumatologi, og dermed ville være effect modifying contextual factors (artikel IV). Vi inkluderede 187 randomiserede forsøg i en meta-epidemiologisk undersøgelse og fandt begrænsede data og få, potentielt misvisende, indikationer på effektmodifikation.5. Til sidst leverede vi en simpel vejledning i statistiske tests af interaktion til at identificere effektmodifikation (subgruppeeffekter) i randomiserede forsøg (artikel V). I vejledningen foreslår vi, at forsøgsrapporter i fremtiden skal estimere behandlingseffekten i forskellige subgrupper for at facilitere nuancerede opsummeringer af evidens, der på sigt kan fremme stratificeret patientbehandling.Vores operationelle definition af kontekstuelle faktorer beskriver tre typer, effect modifying -, outcome influencing - og measurement affecting contextual factors. Vi undersøgte potentielle effect modifying contextual factors på tværs af forsøg, men fandt begrænset evidens, særligt på grund af manglende data. Der er behov for konsekvent og ensartet rapportering af patientkarakteristika i forsøg og gerne estimater for behandlingseffekten i subgrupper. Vores biostatistiske vejledning kan bruges som inspiration. Dette arbejde forventes at fortsætte som tre initiativer, for at udvikle en liste med vigtige faktorer og vejledning for hver type af de kontekstuelle faktorer. Contextual factors are important for understanding trial results. Through the global Outcome Measures in Rheumatology (OMERACT) initiative of international stakeholders interested in outcome measurements and trial design, there is an urgent need for guidance on how to identify contextual factors as part of core outcome set development. This led to the formation of the OMERACT Contextual Factors Working Group.First, we clarified the overall aim of the effort and developed a research plan (paper I). Our main goal was to provide an operational definition and guidance on how to address contextual factors in rheumatology trials as part of developing core outcome sets. Further, we aimed to provide a generic set of important contextual factors that should always be considered in rheumatology trials.Second, we explored perspectives on contextual factors (paper II). Through semi-structured interviews of 12 researchers/clinicians and 7 patients, and qualitative content analysis, we found two overarching themes describing four types of contextual factors, of which three were relevant within OMERACT.Third, we developed a consensus-based operational definition of contextual factors (paper III). We refined the descriptions of the three contextual factor types and involved 33 patients and 128 clinicians/others in a Delphi survey, reaching consensus after two rounds. The contextual factor types were termed effect modifying -, outcome influencing -, and measurement affecting contextual factors.Fourth, we explored whether population characteristics modify treatment response across trials within rheumatology and, hence, may be effect modifying contextual factors (paper IV). We included 187 trials in a meta-epidemiological study and found limited data and few, potentially spurious, indications of effect modification.Finally, we provided a concise and nontechnical (biostatistics) tutorial on the use of statistical tests for interaction to identify effect modifiers (subgroup effects) in randomized trials (paper V). We propose that trial reports in the future should include treatment effect estimates for subgroups to facilitate better evidence synthesis on stratified medicine.In conclusion, our consensus-based operational definition of contextual factors describes three types, effect modifying -, outcome influencing -, and measurement affecting contextual factors. When exploring potential effect modifying contextual factors across trials, we found limited evidence, mainly due to lack of data. There is an urgent need for consistent reporting of population characteristics in trials and, preferably, treatment effect estimates for subgroups. Our simple hands-on guide for investigating effect modifiers may be used as inspiration. This work is expected to continue as three separate workstreams for developing consensus-based generic lists of important factors and guidance for each contextual factor type.

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    Authors: Theussen, Amelie;
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Sodemann, Morten;

    Morten Sodemann giver sit bud på "de første uskrevne patientregler". De er gode at kende, når talen falder på patientinddragelse.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
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    Authors: Schramm, Moritz;
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Alving, Berit Elisabeth; Haastrup, Mette Fentz;

    Indeholder moduler opdelt i temaer, som indeholder links, videoer og tekstuddrag, samt oplæg til refleksion og diskussion. Anvendes internt for partnere under Et Sundere Syddanmark - Gymnasiepanelet.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Lüchau, Elle Christine;
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Jespersen, Christian;

    Afhandlingen analyserer i hvilket omfang Traktatfrihederne forpligter medlemsstaterne til at yde kompensation for underskud til koncerner og til selskaber med faste driftssteder. Afhandlingen er inddelt i otte kapitler. Afhandlingens kapitel 1 præsenterer emnet, problemformulering samt metode.Afhandlingens kapitel 2 introducerer emnet på medlemsstabsniveau. Dette kapitelintroducerer de udfordringer, som - på den ene side - den asymmetriske behandling af overskud og underskud og - på den anden side - de grundlæggende principper for beskatning skaber i relation til fradrag, som skaber et underskud. Herudover beskriver kapitlet de mest almindelige metoder, som anvendes for at yde underskudskompensation. Endelige beskriver kapitlet de udfordringer, som opstår i relation til underskudskompensation, når selskaber og koncerner udøver grænseoverskridende virksomhed. Afhandlingens kapitel 3-5 introducerer de fire friheder og redegør for, hvordan EU domstolen vurderer, om en national skattelovgivning er i uoverensstemmelse med en traktatfrihed. Kapitel 3 introducerer de fire traktatfriheder og redegør for traktatfrihedernes restriktionsbegreb, som dette fortolkes i relation til nationale regler på området for direkte beskatning. På grundlag af dette indledende kapitel uddyber kapitel 4 restriktionstesten, som består af henholdsvis ulempetesten of sammenlignelighedstesten, mens kapitel 5 uddyber justifikationstesten.Afhandlingens kapitel 6-7 analyserer EU-domstolens praksis vedrørende underskudskompensation. Kapitel 6 analyserer i hvilket omfang en medlemsstat er forpligtet til at yde kompensation for underskud lidt af koncerner i grænseoverskridende situationer. Dette afsnit analyserer således EU-domstolens praksis vedrørende horisontalekompensationsordninger samt underskudsanvendelse i forlængelse af en fusion. Kapitel 7 analyserer i hvilket omfang en medlemsstat er forpligtet til at yder kompensation for underskud lidt af et selskab med et fast driftssted. Dette afsnit analyserer EU-domstolens praksis vedrørende fradrag for underskud i det underskudsgivende indkomstår, fradrag for underskud i medfør af vertikale kompensationsordninger, genbeskatning af underskud som allerede er taget i betragtning og udskydelse af beskatning som følge af underskud. The thesis analyses to what extent the Treaty freedoms require the EU Member State to provide loss compensation to corporate groups and to companies with permanent establishments in the European Union. The thesis is divided into eight chapters. The first part of the thesis presents the subject, the research questions, the motivation for the choice of subject, delimitation and legal philosophy and methods.Chapter 2 introduces the subject on Member State-level. This chapter introduces the challenges that are caused by - on the one hand - the asymmetrical treatment of profits and loss and - on the other hand - the fundamental principles of taxation in respect of losses. This chapter further introduces the most common methods adopted in order to provide loss compensation. Finally, the chapter elaborates on the challenges that arise in relation to loss compensation when corporate groups and companies exercise cross-border activity.Chapter 3-5 introduces the four Treaty freedoms and explain how the European Court of justice examines whether a nation legislation on direct taxation violates a Treaty freedom. Chapter 3 introduces the four Treaty freedoms and explains how the European Court of Justice interprets the concept of restriction in respect of national legislation on direct taxation. On that basis, chapter 4 elaborates on the restriction test, which comprises the disadvantage test and the comparability test, while chapter 5 elaborates on the justification test.Chapters 6-7 analyses the case law of the European Court of Justice on loss compensation. Chapter 6 analyses to what extent the Treaty freedoms require a Member State to provide loss compensation to corporate groups in cross-border situations. This chapter analyses the case law on horizontal loss compensation schemes and national provisions providing for loss compensation in the context of a merger. Chapter 7 analyses to what extent a Member State is required to provide loss compensation to a company with a permanent establishment. This chapter analyses the case law concerning deductions of losses during the loss-making income year, deduction of losses by means of horizontal loss compensation schemes, reincorporation of losses previously deduction and the deferral of taxation as a consequence of losses.Chapter 8 contains the conclusion on the thesis. This chapter concludes to what extent the Treaty freedoms require the Member States to provide loss compensation to corporate groups in cross-border situations and to a company with a permanent establishment.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Thøgersen, Dagfinn Mørkrid;

    Conduct problems in adolescence is a well-known phenomenon where a range of negative behaviors can have multiple detrimental effects on the youth themselves, their family members and surroundings. Callous-unemotional (CU) traits have been linked to more severe and persistent antisocial behaviors and are characterized by a lack of empathy, a lack of remorse and guilt, a lack of concern in performance and shallow affect (Frick et al., 2014). Research suggests that there might be a distinct developmental pathway for conduct problems in children with CU traits, evidenced by both neurobiological and -psychological indicators (Frick et al., 2014). This has warranted the addition of the CU-specifier “with limited prosocial emotions” to the conduct disorder. CU traits might thereby provide a more nuanced assessment of risk factors associated with conduct problems and could assist in providing more optimal treatments for youth with these characteristics.This PhD-dissertation had three aims related to CU traits in adolescents. The first aim was to assess the construct validity of a commonly used measure of CU traits, the Inventory of CallousUnemotional traits (ICU), in a Norwegian sample of at-risk adolescents. The second aim was to assess the degree to which CU traits are linked to treatment outcomes among adolescents with behavior problems who receive Functional Family Therapy (FFT). The third aim was to assess the degree of change in CU traits for adolescents participating in FFT. The analyses were based on data from a single group pre-post evaluation of FFT in Denmark (N=407), and a randomized controlled trial of FFT in Norway (N=159-160). Aim 1: The construct validity of the Norwegian translation of the ICU. Previous research is somewhat inconsistent regarding the factorial structure of the ICU and the items on the Unemotional subscale have been particularly scrutinized. The first paper included in this thesis (Paper 1) thus studied the construct validity of the Norwegian translation of the ICU. A multi-informant sample of 160 adolescents and their parents and teachers provided the data for this study. The results from Paper 1 showed that a two-factor solution of a Callousness factor and an Uncaring factor provided the best fit to the model across respondent groups. The Callousness factor was most strongly related to anti-social behavior, while the Uncaring factor was most strongly related to the lack of fear. Despite these distinct correlational patterns, the two-factor structure could be the result of a common method-variance effects related to whether items were standard- or reverse-scored. It is therefore likely that CU traits are best operationalized as a unidimensional measure. Aim 2: The relationship between CU traits and treatment outcomes. The degree to which CU traits impact treatment outcomes for adolescents with behavior problems was the focus of the remaining papers of this thesis (Paper 2 and Paper 3). In both of these there was little evidence to suggest that CU traits were linked to diminished treatment outcomes. On the contrary, CU traits were linked to steeper decreases in anti-social behavior and steeper increases in prosocial behavior in Paper 2. In Paper 3, the relationships between CU traits and treatment outcomes became non-significant when controlling for baseline levels of behavior problems. One possible explanation for these findings is that adolescents with CU traits have more problems at baseline and thereby a greater potential range of improvement. Importantly, the results in Paper 3 showed that although CU traits were either neutrally or positively related to treatment outcomes, baseline CU traits were still predictive of problematic behavior at the end of treatment. This suggests that adolescents with elevated levels of CU traits could be in need of more tailored and long-term services to sustain behavioral improvements over time. The impact of CU traits on treatment outcomes was not different when comparing FFT treatment to an active control condition, when only looking at those with clinical levels of externalizing problems at the start of treatment or when comparing primary to secondary CU subtypologies.Aim 3: The malleability of CU traits. With respect to whether CU traits change over the course of treatment, the results from Paper 2 and Paper 3 were somewhat mixed. In both papers the overall change in CU traits across treatment was small, and a reliable decline in CU traits was observed in relatively few adolescents. At the same time, both papers found more pronounced reductions in CU with respect to both magnitude and the proportion of participants with reliable decreases in CU traits among the subset of adolescents with increased CU traits at baseline. This suggests that CU traits could act as a moderator of the malleability of CU traits. There were no differences in the malleability of CU traits when comparing FFT treatment to an active control condition and when comparing primary to secondary CU sub-typologies.Conclusion: The results from this PhD-dissertation point to the need for continued development of measures of CU traits in both research and clinical settings. Furthermore, the results suggest that adolescents with behavior problems and CU traits do benefit from evidence-based and high-quality treatment, through observed declines in aggressive and rule breaking behavior as well as increases in social skills. Such behavioral improvements seem obtainable without a reduction in the CU traits themselves, as the results indicate that CU traits seem to be relatively stable across time even in the context of treatment. Future work should study the possible benefits of prolonged interventions that specifically target CU-associated risk factors in adolescents, to see if behavioral improvements beyond those obtainable in evidence-based programs and high-quality treatments can be reached. The way in which a reduction in CU traits can be achieved and lead to long-term positive outcomes is also of great importance.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Stærk, Kristian;

    Blærebetændelse er en hyppig infektionssygdom i Danmark og rammer personer i alle aldersgrupper. Selvom blærebetændelse let kan behandles med antibiotika vil sygdommen ofte vende tilbage og vi ved ikke meget om hvorfor nogle personer, som er ellers sunde og raske, bliver ramt og ikke andre. På hospitalerne er blærebetændelse også den hyppigste hospitals-erhvervet infektionssygdom som i høj grad kan tilskrives det store forbrug af urinvejskatetre. Blærebetændelse udgør således et stort problem både i samfundet og på hospitalerne.Målet med dette ph.d.-projekt var at udvikle og optimere en blærebetændelse-model i grise og karakterisere infektionsforløbet og patogenesen i dette dyr mhp. at afdække grisens muligheder som translationel dyremodel inden for denne sygdom.I modellen anvendtes konventionelle hun-grise (Landrace x Yorkshire) på ca. 40 kg. Infektionen blev induceret via transurethral inokulation (via blærekateter) med uropatogene E. coli (UPEC). Grisene blev inokuleret med aftagende mængder bakterier for at identificere det mindste nødvendige inokulum og derved karakterisere grisensfølsom over for blærebetændelse. Ved at bruge en ΔFimH mutant blev betydningen af type-1 fimbriae undersøgt. Tilstedeværelsen af intracellulære bakterier blev undersøgt ved at behandle (med antibiotika) inficerede griseblærer ex vivo eller in vivo og herefter mikroskopere med konfokal laser scanning mikroskopi samt ved udpladning af homogeniseret blærevæv. Grisemodellen blev også tilpasset til at facilitere et studie med et nyt antimikrobielt blærekateter.Resultaterne er sammenskrevet i 5 manuskripter (3 publikationer og 2 manuskripter under fagfællebedømmelse) og viser at grise er meget følsomme for UVI og at kun ganske få bakterier er tilstrækkeligt til at give ophav til blærebetændelse. infektionspotentialet er meget afhængigt at type-1 fimbriae, da ΔFimH mutanten var betydeligt svækket. Intracellulære bakterier kunne ikke påvises I blærevæv. I katetermodellen var det antimikrobielle kateter I stand til at forhindre infektion i alle grise til sammenligning med kontrol grise som alle udviklede blærebetændelse.Konklusionen er, at blærebetændelses-modellen i grise er en pålidelig model som afspejler mange vigtige parametre ved human infektion. Derfor er grisen velegnet til patogenese-studier og som præ-klinisk model til at validerer nye behandlinger mod blærebetændelse. Herudover viser studierne at der er betydeligeforskelle i patogenesen, særligt i forhold til den intracellulære kolonisering, mellem mus og grise og indikerer herved at resultater fra mus ikke altid kan ekstrapoleres direkte til større dyr. Urinary tract infection (UTI), in particular cystitis, is a widespread disease in Denmark and the whole world and occurs in all age groups [1]. UTIs constitutes the most common nosocomial infection, the most common cause of sepsis and accounts for approximately 3000 deaths every year in Denmark alone [3, 133]. Community-acquired UTIs are characterized by a high frequency of recurrence, even in otherwise healthy women with no apparent risk factors [1].A part from epidemiological data, much of what we know about the pathogenesis of UTI comes from experimental studies in cell-culture based assays and murine models of cystitis. In these models, uropathogenic Escherichia coli (UPEC), the most common etiological agent of UTI, has been shown to invade bladder epithelial cells forming intracellular dormant reservoir [134]. In mice, these reservoirs can survive antibiotic treatment and seed re-infections [121]. The intracellular pathogenic cascade has been suggested as a plausible explanation to recurrent UTIs in humans as well. However, despite being extensively demonstrated in mice through the last 20 years, only very few studies has indicated a similar pathogenesis in humans and the hypothesis have struggled to become accepted in clinical societies [134-137]. This may in part be explained by an increasing skepticism towards the translatability of murine models to human disease [4].To bridge the gap between mice and humans, this Ph.D project aimed to investigate UPEC pathogenesis, including the intracellular pathogenic cascade, in a new large animal model of UTI in pigs. Pigs have been highlighted as excellent models of infectious diseases and share more similarities to humans in terms of genetics, immune physiology and urinary tract anatomy compared to their rodent counterpart [7]. Female domestic pigs (Landrace x Yorkshire, mix) of roughly 40 kg were used here. The pigs were inoculated through a urinary catheter with UPEC to induce cystitis. Pigs were inoculated with varying concentrations of bacteria to determine minimal infectious inoculum, i.e. the susceptibility to infection. Furthermore, by using a mutant lacking the T1F, one of the most well-described virulence factors of UPEC, the influence of thisfimbriae on infectious outcome was assessed in the porcine model. To investigate the intracellular pathogenic cascade, whole-bladders from infected pigs were investigated for the presence of intracellular bacteria following ex vivo and in vivo antibiotic treatment by analyzing splayed bladders with confocal laser scanning microscopy and plating homogenized tissue samples. Lastly, the model was adapted to facilitate studies of catheter-associated UTI (CAUTI), and with this, an efficacy study of a novel antimicrobial catheter was performed. The results are consolidated in 5 manuscripts (3 published papers, 2 in peer-review) and show that pigs are highly susceptible to UTI, with only a few single bacteria of UPEC capable of successfully infecting this animal. This infectious potential is largely dependent on T1F, as the T1F-deficient mutant was strongly attenuated. Surprisingly, we found no evidence of intracellular persistence upon antibiotic treatment. In the CAUTImodel, we demonstrate proof-of-concept of an antimicrobial bladder catheter that effectively prevented CAUTI in all pigs.In conclusion, the pig represents a robust model that recapitulates important aspects of human UTI. Thereby, the model is appropriate for studies of UTI pathogenesis as well as pre-clinical efficacy studies of new therapeutic treatments or interventions against UTI. Furthermore, the results of these studies show important differences in UTI pathogenesis between mice and pigs, particular in relation to intracellular persistence and thereby support that results from experiments in mice should be interpreted with caution.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Bøgelund Pedersen, Morten; Esmann Fonvig, Christina; Aagaard, Per; Hansen, Gunhild Mo; +2 Authors
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Mai Nielsen, Sabrina;

    Kontekstuelle faktorer (Eng. contextual factors) er vigtige for at få en dybere forståelse af resultaterne fra kliniske forsøg. Gennem det globale Outcome Measures in Rheumatology (OMERACT)-initiativ er der et presserende behov for vejledning i at identificere kontekstuelle faktorer, når der udvikles såkaldte core outcome sets (dvs. et minimum set af målinger der skal foretages i kliniske forsøg). Dette førte til dannelsen af OMERACT-arbejdsgruppen, Contextual Factors Working Group.1. Først præciserede vi det overordnede formål for arbejdsgruppen og udviklede en forskningsplan (artikel I). Hovedformålet var at udvikle en operationel definition og vejledning i at håndtere kontekstuelle faktorer i forsøg indenfor reumatologi, når der udvikles core outcome sets. Derudover ønskede vi at udvikle et generisk sæt af vigtige kontekstuelle faktorer for reumatologiske forsøg.2. Vi undersøgte forskellige forståelser af begrebet kontekstuelle faktorer (artikel II). Ved hjælp af semistrukturerede interviews med 12 forskere/klinikere og 7 patienter, samt kvalitativ indholdsanalyse af interviewdataene, fandt vi to overordnede temaer, der tilsammen beskriver fire forskellige typer af kontekstuelle faktorer, hvoraf tre var relevante indenfor OMERACT.3. Vi udviklede en operationel definition af kontekstuelle faktorer (artikel III). Beskrivelserne for de tre typer blev finpudset, og vi gennemførte et Delphi-studie med 33 patienter og 128 klinikere/øvrige. Efter to Delphi-runder var der opnået konsensus. De tre faktortyper blev kaldt effect modifying -, outcome influencing - og measurement affecting contextual factors, som på dansk kan formidles som hhv. effekt-modificerende -, udfalds-influerende og målings-påvirkende kontekstuelle faktorer.4. Vi undersøgte en række patientkarakteristika for, om de kunne ændre behandlingseffekten på tværs af forsøg indenfor reumatologi, og dermed ville være effect modifying contextual factors (artikel IV). Vi inkluderede 187 randomiserede forsøg i en meta-epidemiologisk undersøgelse og fandt begrænsede data og få, potentielt misvisende, indikationer på effektmodifikation.5. Til sidst leverede vi en simpel vejledning i statistiske tests af interaktion til at identificere effektmodifikation (subgruppeeffekter) i randomiserede forsøg (artikel V). I vejledningen foreslår vi, at forsøgsrapporter i fremtiden skal estimere behandlingseffekten i forskellige subgrupper for at facilitere nuancerede opsummeringer af evidens, der på sigt kan fremme stratificeret patientbehandling.Vores operationelle definition af kontekstuelle faktorer beskriver tre typer, effect modifying -, outcome influencing - og measurement affecting contextual factors. Vi undersøgte potentielle effect modifying contextual factors på tværs af forsøg, men fandt begrænset evidens, særligt på grund af manglende data. Der er behov for konsekvent og ensartet rapportering af patientkarakteristika i forsøg og gerne estimater for behandlingseffekten i subgrupper. Vores biostatistiske vejledning kan bruges som inspiration. Dette arbejde forventes at fortsætte som tre initiativer, for at udvikle en liste med vigtige faktorer og vejledning for hver type af de kontekstuelle faktorer. Contextual factors are important for understanding trial results. Through the global Outcome Measures in Rheumatology (OMERACT) initiative of international stakeholders interested in outcome measurements and trial design, there is an urgent need for guidance on how to identify contextual factors as part of core outcome set development. This led to the formation of the OMERACT Contextual Factors Working Group.First, we clarified the overall aim of the effort and developed a research plan (paper I). Our main goal was to provide an operational definition and guidance on how to address contextual factors in rheumatology trials as part of developing core outcome sets. Further, we aimed to provide a generic set of important contextual factors that should always be considered in rheumatology trials.Second, we explored perspectives on contextual factors (paper II). Through semi-structured interviews of 12 researchers/clinicians and 7 patients, and qualitative content analysis, we found two overarching themes describing four types of contextual factors, of which three were relevant within OMERACT.Third, we developed a consensus-based operational definition of contextual factors (paper III). We refined the descriptions of the three contextual factor types and involved 33 patients and 128 clinicians/others in a Delphi survey, reaching consensus after two rounds. The contextual factor types were termed effect modifying -, outcome influencing -, and measurement affecting contextual factors.Fourth, we explored whether population characteristics modify treatment response across trials within rheumatology and, hence, may be effect modifying contextual factors (paper IV). We included 187 trials in a meta-epidemiological study and found limited data and few, potentially spurious, indications of effect modification.Finally, we provided a concise and nontechnical (biostatistics) tutorial on the use of statistical tests for interaction to identify effect modifiers (subgroup effects) in randomized trials (paper V). We propose that trial reports in the future should include treatment effect estimates for subgroups to facilitate better evidence synthesis on stratified medicine.In conclusion, our consensus-based operational definition of contextual factors describes three types, effect modifying -, outcome influencing -, and measurement affecting contextual factors. When exploring potential effect modifying contextual factors across trials, we found limited evidence, mainly due to lack of data. There is an urgent need for consistent reporting of population characteristics in trials and, preferably, treatment effect estimates for subgroups. Our simple hands-on guide for investigating effect modifiers may be used as inspiration. This work is expected to continue as three separate workstreams for developing consensus-based generic lists of important factors and guidance for each contextual factor type.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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    Authors: Theussen, Amelie;
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao University of Southe...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Sodemann, Morten;

    Morten Sodemann giver sit bud på "de første uskrevne patientregler". De er gode at kende, når talen falder på patientinddragelse.

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