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INTRODUCTION: Solitary fibrous tumor (SFT) is a rare soft tissue tumor found at any site of the body. The treatment of choice is surgical resection, though 10%-30% of patients experience recurrent disease. Multiple risk factors and risk stratification systems have been investigated to predict which patients are at risk of recurrence. The main goal of this systematic review is to create an up-to-date systematic overview of risk factors and risk stratification systems predicting recurrence for patients with surgically resected SFT within torso and extremities.METHOD: We prepared the review following the updated Prisma guidelines for systematic reviews (PRISMA-P). Pubmed, Embase, Cochrane Library, WHO international trial registry platform and ClinicalTrials.gov were systematically searched up to December 2022. All English studies describing risk factors for recurrence after resected SFT were included. We excluded SFT in the central nervous system and the oto-rhino-laryngology region.RESULTS: Eighty-one retrospective studies were identified. Different risk factors including age, symptoms, sex, resection margins, anatomic location, mitotic index, pleomorphism, hypercellularity, necrosis, size, dedifferentiation, CD-34 expression, Ki67 index and TP53-expression, APAF1-inactivation, TERT promoter mutation and NAB2::STAT6 fusion variants were investigated in a narrative manner. We found that high mitotic index, Ki67 index and presence of necrosis increased the risk of recurrence after surgically resected SFT, whereas other factors had more varying prognostic value. We also summarized the currently available different risk stratification systems, and found eight different systems with a varying degree of ability to stratify patients into low, intermediate or high recurrence risk.CONCLUSION: Mitotic index, necrosis and Ki67 index are the most solid risk factors for recurrence. TERT promoter mutation seems a promising component in future risk stratifica

INTRODUCTION: Solitary fibrous tumor (SFT) is a rare soft tissue tumor found at any site of the body. The treatment of choice is surgical resection, though 10%-30% of patients experience recurrent disease. Multiple risk factors and risk stratification systems have been investigated to predict which patients are at risk of recurrence. The main goal of this systematic review is to create an up-to-date systematic overview of risk factors and risk stratification systems predicting recurrence for patients with surgically resected SFT within torso and extremities.METHOD: We prepared the review following the updated Prisma guidelines for systematic reviews (PRISMA-P). Pubmed, Embase, Cochrane Library, WHO international trial registry platform and ClinicalTrials.gov were systematically searched up to December 2022. All English studies describing risk factors for recurrence after resected SFT were included. We excluded SFT in the central nervous system and the oto-rhino-laryngology region.RESULTS: Eighty-one retrospective studies were identified. Different risk factors including age, symptoms, sex, resection margins, anatomic location, mitotic index, pleomorphism, hypercellularity, necrosis, size, dedifferentiation, CD-34 expression, Ki67 index and TP53-expression, APAF1-inactivation, TERT promoter mutation and NAB2::STAT6 fusion variants were investigated in a narrative manner. We found that high mitotic index, Ki67 index and presence of necrosis increased the risk of recurrence after surgically resected SFT, whereas other factors had more varying prognostic value. We also summarized the currently available different risk stratification systems, and found eight different systems with a varying degree of ability to stratify patients into low, intermediate or high recurrence risk.CONCLUSION: Mitotic index, necrosis and Ki67 index are the most solid risk factors for recurrence. TERT promoter mutation seems a promising component in future risk stratifica

Background: Chemotherapy is ineffective in treating patients with Gastrointestinal Stromal Tumor (GIST). However, several types of tyrosine kinase inhibitors have been investigated since the approval of imatinib in 2001. The purpose of this report was to systematically review studies on the efficacy of neoadjuvant, adjuvant, and lifelong medical oncological treatment of GIST. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed throughout the review process. The protocol was submitted to the International prospective register of systematic reviews database (ID 251724). A systematic literature search was performed, including phase II- and III studies of biological treatment, reporting on treatment effect in patients with GIST. Results: Of 308 identified publications, 42 studies were included in this review. Conclusion: This review gives an overview of the existing evidence for approved lines of oncological treatments and potential alternatives for patients with GIST in the neoadjuvant-, adjuvant- and life-long setting.

Background/Aim: For patients with local gastrointestinal stromal tumor (GIST), risk stratification is used to assess the prognosis and identify patients to offer adjuvant treatment. For patients with advanced or metastatic GIST, no such risk stratification exists. This study aimed to investigate the prognostic value of 31 different plasma small extracellular vesicles' (SEVs) surface proteins in GIST patients. Materials and Methods: GIST patients from the two sarcoma centers in Denmark were included. Patients were divided into three groups; group 1: patients undergoing radical surgery; group 2: patients with local, locally advanced, or metastatic GIST; and group 3: patients without evidence of disease after radical surgery. Protein microarray technology was used for the analysis of plasma SEVs. The median plasma SEV marker level was used when comparing groups of patients. The primary endpoint was the progression of GIST. Iterative statistical modeling was used to identify a SEV marker profile/model with a prognostic value. Results: A total of 157 patients were included, with a median follow-up time of 2.05 years. In group 2, a high level of carcinoembryonic antigen (CEA) and a low level of glucose transporter 1 (GLUT-1) were found to be poor prognostic factors [univariate analysis; GLUT-1: hazard ratio (HR)=0.47, 95% confidence interval (CI)=0.22-0.98; CEA: HR=2.12, 95%CI=1.02-4.44]. Composing a model consisting of CEA and GLUT-1 adjusted for age at inclusion was found to have a prognostic value (HR=4.93, 95%CI=2.30-10.57, p<0.0001). Conclusion: Plasma SEVs in GIST showed that CEA and GLUT-1 might be of prognostic value. However, external validation is needed.

Background: This study investigates the prognostic value of plasma Programmed Death Protein-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) concentrations in patients with Gastrointestinal Stromal Tumor (GIST). Methods: Patients with GIST were included (n = 157) from the two Danish sarcoma centers, independent of disease- and treatment status. The patients were divided into three subgroups; 1: patients with localized disease who underwent radical surgery; 2: patients with local, locally advanced, or metastatic disease; and 3: patients without measurable disease who had undergone radical surgery. Sensitive electrochemiluminescence immune-assays were used to determine PD-1 and PD-L1 concentration in plasma samples. The primary endpoint was the PFS. Results: No patients progressed in group 1 (n = 15), 34 progressed in group 2 (n = 122), and three progressed in group 3 (n = 20). Significantly higher plasma concentrations of PD-1 (p = 0.0023) and PD-L1 (0.012) were found in patients in group 2 compared to PD-1/PD-L1 levels in postoperative plasma samples from patient group 1. Patients with active GIST having a plasma concentration of PD-L1 above the cutoff (225 pg/mL) had a significantly poorer prognosis compared to patients with plasma PD-L1 concentration below the cutoff. Conclusions: Plasma PD-L1 shows potential as a prognostic biomarker in patients with GIST and should be further evaluated.

Background/Aim: Gastrointestinal stromal tumours (GISTs) harbour genetic aberrations in receptor tyrosine kinase KIT (KIT) or platelet-derived growth factor receptor A (PDGFRA) in 85-90% of the patients. Circulating tumour DNA (ctDNA) is a potential biomarker in patients with GIST. Previous studies investigating ctDNA around surgery in patients with GIST presented divergent results regarding the proportion of patients with detectable ctDNA. This study aimed to 1) investigate the feasibility of detecting and monitoring ctDNA pre-and postoperative, 2) compare two different circulating free DNA (cfDNA) extraction methods, and validate results obtained by next-generation sequencing (NGS) using Real-Time PCR technology. Patients and Methods: Eight patients planned for immediate surgery or surgery after neoadjuvant oncological treatment were included in the study, from whom blood collection was performed pre- and postoperatively for ctDNA analysis. Furthermore, blood samples from six patients with GIST harbouring a point mutation in KIT or PDGFRA in tissues from primary tumours were used for comparison and validation sub-study. Results: In this explorative study, none of the patients with very low to intermediate risk GIST harboured KIT, or PDGFRA mutated ctDNA in pre-or postoperative blood samples. The methods used for cfDNA extraction gave similar output, and the two methods for ctDNA analysis gave identical results. Conclusion: There is no benefit in analysing ctDNA around surgery in very low to intermediate-risk GIST patients. Larger studies investigating ctDNA in patients with high-risk GIST around surgery are warranted.

Background/Aim: For patients with local gastrointestinal stromal tumor (GIST), risk stratification is used to assess the prognosis and identify patients to offer adjuvant treatment. For patients with advanced or metastatic GIST, no such risk stratification exists. This study aimed to investigate the prognostic value of 31 different plasma small extracellular vesicles' (SEVs) surface proteins in GIST patients. Materials and Methods: GIST patients from the two sarcoma centers in Denmark were included. Patients were divided into three groups; group 1: patients undergoing radical surgery; group 2: patients with local, locally advanced, or metastatic GIST; and group 3: patients without evidence of disease after radical surgery. Protein microarray technology was used for the analysis of plasma SEVs. The median plasma SEV marker level was used when comparing groups of patients. The primary endpoint was the progression of GIST. Iterative statistical modeling was used to identify a SEV marker profile/model with a prognostic value. Results: A total of 157 patients were included, with a median follow-up time of 2.05 years. In group 2, a high level of carcinoembryonic antigen (CEA) and a low level of glucose transporter 1 (GLUT-1) were found to be poor prognostic factors [univariate analysis; GLUT-1: hazard ratio (HR)=0.47, 95% confidence interval (CI)=0.22-0.98; CEA: HR=2.12, 95%CI=1.02-4.44]. Composing a model consisting of CEA and GLUT-1 adjusted for age at inclusion was found to have a prognostic value (HR=4.93, 95%CI=2.30-10.57, p<0.0001). Conclusion: Plasma SEVs in GIST showed that CEA and GLUT-1 might be of prognostic value. However, external validation is needed.

Background: This study investigates the prognostic value of plasma Programmed Death Protein-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) concentrations in patients with Gastrointestinal Stromal Tumor (GIST). Methods: Patients with GIST were included (n = 157) from the two Danish sarcoma centers, independent of disease- and treatment status. The patients were divided into three subgroups; 1: patients with localized disease who underwent radical surgery; 2: patients with local, locally advanced, or metastatic disease; and 3: patients without measurable disease who had undergone radical surgery. Sensitive electrochemiluminescence immune-assays were used to determine PD-1 and PD-L1 concentration in plasma samples. The primary endpoint was the PFS. Results: No patients progressed in group 1 (n = 15), 34 progressed in group 2 (n = 122), and three progressed in group 3 (n = 20). Significantly higher plasma concentrations of PD-1 (p = 0.0023) and PD-L1 (0.012) were found in patients in group 2 compared to PD-1/PD-L1 levels in postoperative plasma samples from patient group 1. Patients with active GIST having a plasma concentration of PD-L1 above the cutoff (225 pg/mL) had a significantly poorer prognosis compared to patients with plasma PD-L1 concentration below the cutoff. Conclusions: Plasma PD-L1 shows potential as a prognostic biomarker in patients with GIST and should be further evaluated.

Background: Chemotherapy is ineffective in treating patients with Gastrointestinal Stromal Tumor (GIST). However, several types of tyrosine kinase inhibitors have been investigated since the approval of imatinib in 2001. The purpose of this report was to systematically review studies on the efficacy of neoadjuvant, adjuvant, and lifelong medical oncological treatment of GIST. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed throughout the review process. The protocol was submitted to the International prospective register of systematic reviews database (ID 251724). A systematic literature search was performed, including phase II- and III studies of biological treatment, reporting on treatment effect in patients with GIST. Results: Of 308 identified publications, 42 studies were included in this review. Conclusion: This review gives an overview of the existing evidence for approved lines of oncological treatments and potential alternatives for patients with GIST in the neoadjuvant-, adjuvant- and life-long setting.

Overexpressed genes may be useful for monitoring of measurable residual disease (MRD) in patients with childhood acute myeloid leukemia (AML) without a leukemia-specific target. The normal expression of five leukemia-associated genes (SPAG6, ST18, MSLN, PRAME, XAGE1A) was defined in children without hematologic disease (n = 53) and children with suspected infection (n = 90). Gene expression at AML diagnosis (n=50) and during follow-up (n = 21) was compared with child-specific reference values. At diagnosis, 34/50 children (68%) had high expression of at least one of the five genes, and so did 16/31 children (52%) without a leukemia-specific target. Gene expression was quantified in 110 peripheral blood (PB) samples (median, five samples/patient; range, 1 to 10) during follow-up in 21 patients with high expression at diagnosis. All nine patients with PB sampling performed within 100 days of disease recurrence displayed overexpression of SPAG6, ST18, PRAME, or XAGE1A at a median of 2 months (range, 0.6 to 9.6 months) before hematologic relapse, whereas MSLN did not reach expression above normal prior to hematologic relapse. Only 1 of 130 (0.8%) follow-up analyses performed in 10 patients in continuous complete remission had transient expression above normal. SPAG6, ST18, PRAME, and XAGE1A expression in PB may predict relapse in childhood AML patients and facilitate MRD monitoring in most patients without a leukemia-specific target.

Background: Cancer patients are vulnerable to infections, are older and often have comorbidities in comparison to the general population, which increases the risk for severe outcomes related to COVID-19 diagnosis. Methods: This study is a prospective, nationwide study in patients with solid cancer and SARS-CoV-2 infection included between 10 March to 15 June 2020. Patient's baseline characteristics were collected. The study’s primary outcome was overall survival within 30 days of verified SARS-CoV-2 infection. Secondary outcomes were hospital admission, admission to an ICU, and need for supplemental oxygen. Results: A total of 112 patients with a cancer diagnosis and verified SARS-CoV-2 infection were identified. After one month of follow up, hospitalization was required for 54% (n = 61) and 21% of the patients had died and 14 of the 23 deceased cancer patients were ≥70 years. Most patients were classified with mild COVID-19 symptoms (66%, n = 74); however, 48% (n = 23) of the ≥70-year-olds patients were classified with severe or critical COVID-19 symptoms. Among the total study population, 61% (n = 68) had comorbidities and comorbidity were more frequently observed among the deceased (91%, n = 21) and older cancer patients (≥70 years, 81%, n = 39). Conclusions: Acknowledging the low sample size in this study, our work shows that age and comorbidities, but not recent cytotoxic therapy, are associated with adverse outcomes of SARS-CoV-2 infection for patients with solid cancer. Particularly, patients with progressive disease seem to be at greater risk of a fatal outcome from COVID-19.Highlights Age, performance status, and comorbidities are strong predictors of adverse outcome in cancer patients with SARS-CoV-2 infection. Patients with progressive cancer disease seem to be at greater risk of a fatal outcome from COVID-19. Recent cytotoxic therapy, however, did not seem to be associated with increased risk for adverse outcomes of SARS-CoV-2 infection for patients w

Smertebehandling i odontologisk regi indebærer dels at kunne forudse forventet smerteintensitet efter odontologisk behandling samt, når smerter opstår, dels at kunne afdække årsagen til smerten, vurdere smertens intensitet samt anvise en effektiv protokol til håndtering af smerterne. En basal forståelse af de farmakologiske mekanismer er essentiel for udformningen af en effektiv smertekontrol. Artiklen omhandler medicinsk håndtering af akutte nociceptive smerter og gennemgår de enkelte analgetikas virkningsmekanismer og smertelindrende effekt. I overensstemmelse med Sundhedsstyrelsens seneste retningslinjer for akut smertebehandling, anbefales at bruge af morfin som førstevalg frem for prodrugs som kodein og tramadol, når opioidbehandling er indiceret. Der gives konkrete anbefalinger til dosering, der eksemplificeres ved hypotetiske/konstruerede smertescenarier.

Background: Cancer patients are vulnerable to infections, are older and often have comorbidities in comparison to the general population, which increases the risk for severe outcomes related to COVID-19 diagnosis. Methods: This study is a prospective, nationwide study in patients with solid cancer and SARS-CoV-2 infection included between 10 March to 15 June 2020. Patient's baseline characteristics were collected. The study’s primary outcome was overall survival within 30 days of verified SARS-CoV-2 infection. Secondary outcomes were hospital admission, admission to an ICU, and need for supplemental oxygen. Results: A total of 112 patients with a cancer diagnosis and verified SARS-CoV-2 infection were identified. After one month of follow up, hospitalization was required for 54% (n = 61) and 21% of the patients had died and 14 of the 23 deceased cancer patients were ≥70 years. Most patients were classified with mild COVID-19 symptoms (66%, n = 74); however, 48% (n = 23) of the ≥70-year-olds patients were classified with severe or critical COVID-19 symptoms. Among the total study population, 61% (n = 68) had comorbidities and comorbidity were more frequently observed among the deceased (91%, n = 21) and older cancer patients (≥70 years, 81%, n = 39). Conclusions: Acknowledging the low sample size in this study, our work shows that age and comorbidities, but not recent cytotoxic therapy, are associated with adverse outcomes of SARS-CoV-2 infection for patients with solid cancer. Particularly, patients with progressive disease seem to be at greater risk of a fatal outcome from COVID-19.Highlights Age, performance status, and comorbidities are strong predictors of adverse outcome in cancer patients with SARS-CoV-2 infection. Patients with progressive cancer disease seem to be at greater risk of a fatal outcome from COVID-19. Recent cytotoxic therapy, however, did not seem to be associated with increased risk for adverse outcomes of SARS-CoV-2 infection for patients w

Smertebehandling i odontologisk regi indebærer dels at kunne forudse forventet smerteintensitet efter odontologisk behandling samt, når smerter opstår, dels at kunne afdække årsagen til smerten, vurdere smertens intensitet samt anvise en effektiv protokol til håndtering af smerterne. En basal forståelse af de farmakologiske mekanismer er essentiel for udformningen af en effektiv smertekontrol. Artiklen omhandler medicinsk håndtering af akutte nociceptive smerter og gennemgår de enkelte analgetikas virkningsmekanismer og smertelindrende effekt. I overensstemmelse med Sundhedsstyrelsens seneste retningslinjer for akut smertebehandling, anbefales at bruge af morfin som førstevalg frem for prodrugs som kodein og tramadol, når opioidbehandling er indiceret. Der gives konkrete anbefalinger til dosering, der eksemplificeres ved hypotetiske/konstruerede smertescenarier.

Since March 2020, most physical education (PE) teachers in Scandinavia have faced the challenges of remote teaching. Homeschooling has perhaps been particularly challenging for PE teachers compared to other teachers, given the essential role of bodily contact, interaction, social negotiations, game playing and shared expressions in PE (Varea and González-Calvo, 2020). Having worked with covid conditions for a year now, we trust that teachers have worked out various solutions that, we hope, are relevant and meaningful for the students. At the same time, both from our personal experiences and early research findings (Mercier et al. 2021), it appears that PE teachers have largely provided students with physical activity and fitness training during the pandemic. In this short text, we want to share an idea for a concrete alternative to fitness exercises, which, although important, is only one part of the PE curriculum. It springs from a pedagogical model we outlined in a double article from 2018, which focuses on practising. Practising, which in German is üben and in the Scandinavian languages øve/öva, is, briefly put, a form of activity in which you seek to improve some part of yourself through repeated efforts. Recently, one of our colleagues, Dillon Landi, made us aware that this practising model is particularly relevant for teaching during the pandemic. While we did not have remote teaching in mind when we outlined the model, we realise now that it could be a relevant way of coping with the current situation. It can, we believe, guide how teachers can facilitate movement activities for students at home that are both meaningful and educationally relevant. In the following, we will describe what remote teaching with a focus on practising might look like. We hope it can inspire teaching methods that add to the list of pedagogical options available for teachers during the pandemic.

PURPOSE: A rapidly increasing use of biological drugs has led to substantial costs. Shift to biosimilars enables considerable reduction of these costs without jeopardizing the treatment of patients, but most countries have extensive possibilities of untapped cost-savings. The aim of this study was to describe the Danish quick and near-complete implementation of the two first TNF inhibitor biosimilars (infliximab and etanercept).METHODS: We shed light on the considerations and experiences made during the implementation, and present key figures from the implementation.RESULTS: The infliximab biosimilar constituted 90.6% of the total amount of infliximab four months following patent expiration of the biooriginator. Similar results were seen for etanercept biosimilar. Substantial cost reductions were experienced in the way that e.g. the infliximab-shift reduced cost by two thirds.CONCLUSION: We believe that a thorough preparation and an organizational setting supporting the implementation is crucial for the successful implementation. This same implementation model will be used for future biosimilars.

PURPOSE: A rapidly increasing use of biological drugs has led to substantial costs. Shift to biosimilars enables considerable reduction of these costs without jeopardizing the treatment of patients, but most countries have extensive possibilities of untapped cost-savings. The aim of this study was to describe the Danish quick and near-complete implementation of the two first TNF inhibitor biosimilars (infliximab and etanercept).METHODS: We shed light on the considerations and experiences made during the implementation, and present key figures from the implementation.RESULTS: The infliximab biosimilar constituted 90.6% of the total amount of infliximab four months following patent expiration of the biooriginator. Similar results were seen for etanercept biosimilar. Substantial cost reductions were experienced in the way that e.g. the infliximab-shift reduced cost by two thirds.CONCLUSION: We believe that a thorough preparation and an organizational setting supporting the implementation is crucial for the successful implementation. This same implementation model will be used for future biosimilars.

PURPOSE: A rapidly increasing use of biological drugs has led to substantial costs. Shift to biosimilars enables considerable reduction of these costs without jeopardizing the treatment of patients, but most countries have extensive possibilities of untapped cost-savings. The aim of this study was to describe the Danish quick and near-complete implementation of the two first TNF inhibitor biosimilars (infliximab and etanercept).METHODS: We shed light on the considerations and experiences made during the implementation, and present key figures from the implementation.RESULTS: The infliximab biosimilar constituted 90.6% of the total amount of infliximab four months following patent expiration of the biooriginator. Similar results were seen for etanercept biosimilar. Substantial cost reductions were experienced in the way that e.g. the infliximab-shift reduced cost by two thirds.CONCLUSION: We believe that a thorough preparation and an organizational setting supporting the implementation is crucial for the successful implementation. This same implementation model will be used for future biosimilars.

Background: Paraganglioma of the head and neck (HNPGL) are rare often benign tumors. Surgery and radiation therapy (RT) are the main treatment choices. We present an analysis of outcome and toxicity after RT from 13 institutions of the Rare Cancer Network. Methods: Data were collected using a questionnaire concerning patients' characteristics, treatment, and outcome. A total of 81 patients with 82 HNPGL were analyzed. Results: The median follow-up was 48 months (1-456). Sixty-two lesions were treated with conventional RT and 20 lesions with stereotactic RT. Local control (LC) was achieved in 69 out of 77 lesions. Late toxicity occurred in 17 patients. Patients treated with stereotactic RT experienced neither disease progression nor late toxicity. Four patients with a follow-up longer than 20 years experienced disease progression. Conclusion: RT for HNPGL offered good local control with acceptable toxicity. Stereotactic RT might offer better results. Long-term follow-up is required., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

SCOPUS: le.j, DecretOANoAutActif, info:eu-repo/semantics/published

Denne plan for fiskepleje er udarbejdet på baggrund af undersøgelser over den fiskebiologiske tilstand i Halkær Å vandsystemet. Undersøgelsen er foretaget i perioden fra den 27. august til den 13. september 2018 af DTU Aqua, Institut for Akvatiske Ressourcer, Sektion for Ferskvandsfiskeri og - økologi, kaldet DTU Aqua i resten af denne rapport. Medlemmer af Halkær Å Lystfiskerforening, Lystfiskerforeningen Binderup Aa, Sportsfiskerforeningen Salar samt Rebild og Aalborg Kommune har assisteret med feltarbejdet eller været behjælpelige med oplysninger om vandløbsrestaureringer og passageforhold. Denne plan for fiskepleje i Halkær Å er en revision af den tidligere udsætningsplan for Halkær Å fra 2010. Planen er udarbejdet som led i de aktiviteter, der sker i forbindelse med den generelle fiskepleje, herunder restaurering af vandløb ved udlægning af gydebanker m.m. Udsætninger i vandløbene bliver varetaget af Halkær Å Lystfiskerforening. Foreningen opfiskede moderfisk i 2016, og siden er der ikke opfisket moderfisk. Afkom fra disse moderfisk blev udsat som yngel og ½-års i 2017 og mundingsudsatte smolt i foråret 2018.

Background: Models-based approaches to physical education have in recent years developed as a way for teachers and students to concentrate on a manageable number of learning objectives, and align pedagogical approaches with learning subject matter and context. This paper draws on Hannah Arendt’s account ofvita activato map existing approaches to physical education as oriented towards: (a) health and exercise, (b) sport and games, and (c) experience and exploration. Purpose: The aim of the paper is to outline a new pedagogical model for physical education:a practising model. We argue that the form of human activity related to practising is not well represented in existing orientations and models. To sustain this argument, we highlight the most central aspects of practising, and at the same time describe central features of the model. Relevance and implications: The paper addresses pedagogical implications the practising model has for physical education teachers. Central learning outcomes and teaching strategies related to four essential and ‘non-negotiable’ features of the practising model are discussed. These strategies are: (1) acknowledging subjectivity and providing meaningful challenges, (2) focusing on content and the aims of practising, (3) specifying and negotiating standards of excellence and (4) providing adequate time to practising. Conclusion: The practising model has the potential to inform new perspectives on pedagogical approaches, and renew and improve working methods and learning practices, in physical education.

Background: Physical educators currently have a number of pedagogical (or curricular) models at their disposal. While existing models have been well-received in educational contexts, these models seek to extend students’ capacities within a limited number of ‘human activities’ (Arendt, 1958). The activity of human practising, which is concerned with the improvement of the self, is not explicitly dealt with by current models. Purpose: The aim of the paper is to outline how a model of human practising related to movement capability could be enacted in physical education. Findings: Building on a theoretical exposition of human practising presented in a separate paper, this paper provides a practically oriented discussion related to: (1) the general learning outcomes as well as teaching and learning strategies of the model; (2) an outline of five activities that describe how the model could be implemented; and (3) the non-negotiable features of the model. Discussion: The model’s potential contribution to the ongoing revitalization of PE as an institutionalized educational practice is discussed. Points concerning how the model relates to wider physical cultures, its position regarding transfer of learning, standards of excellence, and social and cultural transmission are considered. Conclusion: The paper is concluded with some reflections on pedagogical models generally and how they relate to the pedagogical model of practising movement capability presented in this paper.

Background: Models-based approaches to physical education have inrecent years developed as a way for teachers and students toconcentrate on a manageable number of learning objectives, and alignpedagogical approaches with learning subject matter and context. Thispaper draws on Hannah Arendt’s account of vita activa to map existingapproaches to physical education as oriented towards: (a) health andexercise, (b) sport and games, and (c) experience and exploration.Purpose: The aim of the paper is to outline a new pedagogical model forphysical education: a practising model. We argue that the form of humanactivity related to practising is not well represented in existingorientations and models. To sustain this argument, we highlight themost central aspects of practising, and at the same time describe centralfeatures of the model.Relevance and implications: The paper addresses pedagogicalimplications the practising model has for physical education teachers.Central learning outcomes and teaching strategies related to fouressential and ‘non-negotiable’ features of the practising model arediscussed. These strategies are: (1) acknowledging subjectivity andproviding meaningful challenges, (2) focusing on content and the aimsof practising, (3) specifying and negotiating standards of excellence and(4) providing adequate time to practising.Conclusion: The practising model has the potential to inform newperspectives on pedagogical approaches, and renew and improveworking methods and learning practices, in physical education.

Background: Physical educators currently have a number of pedagogical(or curricular) models at their disposal. While existing models have beenwell-received in educational contexts, these models seek to extendstudents’ capacities within a limited number of ‘human activities’(Arendt, 1958). The activity of human practising, which is concerned withthe improvement of the self, is not explicitly dealt with by current models.Purpose: The aim of the paper is to outline how a model of humanpractising related to movement capability could be enacted in physicaleducation.Findings: Building on a theoretical exposition of human practisingpresented in a separate paper, this paper provides a practically orienteddiscussion related to: (1) the general learning outcomes as well asteaching and learning strategies of the model; (2) an outline of fiveactivities that describe how the model could be implemented; and (3)the non-negotiable features of the model.Discussion: The model’s potential contribution to the ongoingrevitalization of PE as an institutionalized educational practice isdiscussed. Points concerning how the model relates to wider physicalcultures, its position regarding transfer of learning, standards ofexcellence, and social and cultural transmission are considered.Conclusion: The paper is concluded with some reflections onpedagogical models generally and how they relate to the pedagogicalmodel of practising movement capability presented in this paper.

Linn Håkonsen Arendt,1,2,* Andreas Ernst,1,3,* Morten Søndergaard Lindhard,2 Anne Aggerholm Jønsson,1 Tine Brink Henriksen,2 Jørn Olsen,4 Jorgen Thorup,5 L Henning Olsen,3 Cecilia Høst Ramlau-Hansen1 *These authors contributed equally to this work 1Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark; 2Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark; 3Department of Urology, Section for Paediatric Urology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 5Department of Paediatric Surgery, Rigshospitalet and Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark Purpose: The Danish National Health registers provide a valuable data source that offers unique opportunities for observational research, including studies on the congenital anomaly hypospadias. The accuracy of the diagnosis and surgical treatment registration of hypospadias in the Danish National Patient Register (DNPR) remains unknown. Patients and methods: We randomly sampled 500 patients diagnosed with hypospadias in the DNPR from January 1, 1995 to December 31, 2012. Among these, 384 patients were also registered with surgical treatment for hypospadias. Medical records were collected and reviewed independently by two investigators. Any classification disagreements were resolved by consensus. Using the medical records as the gold standard, we estimated positive predictive values (PPVs) with 95% confidence intervals (CIs) for the hypospadias diagnoses and surgical treatment registrations overall, as well as for the clinical subtypes. Results: We were able to retrieve medical records for 463 (92.6%) patients with hypospadias diagnoses and for 329 (85.7%) patients registered with surgical treatment. Presence of hypospadias was confirmed in 450 of 463 patients, yielding an o

Purpose: The Danish National Health registers provide a valuable data source that offers unique opportunities for observational research, including studies on the congenital anomaly hypospadias. The accuracy of the diagnosis and surgical treatment registration of hypospadias in the Danish National Patient Register (DNPR) remains unknown. Patients and methods: We randomly sampled 500 patients diagnosed with hypospadias in the DNPR from January 1, 1995 to December 31, 2012. Among these, 384 patients were also registered with surgical treatment for hypospadias. Medical records were collected and reviewed independently by two investigators. Any classification disagreements were resolved by consensus. Using the medical records as the gold standard, we estimated positive predictive values (PPVs) with 95% confidence intervals (CIs) for the hypospadias diagnoses and surgical treatment registrations overall, as well as for the clinical subtypes. Results: We were able to retrieve medical records for 463 (92.6%) patients with hypospadias diagnoses and for 329 (85.7%) patients registered with surgical treatment. Presence of hypospadias was confirmed in 450 of 463 patients, yielding an overall PPV (95% CI) of 97.6% (95.8%–98.7%). For subtypes of hypospadias, the PPVs ranged between 37.5% and 72.7%. For surgical treatment of hypospadias, the overall PPV was 99.7% (97.9%–99.9%). Conclusion: The validity of the registration of hypospadias diagnoses as well as surgical treatment for hypospadias in the DNPR is overall very high. For the specific subtypes of hypospadias diagnoses codes and the specific surgical treatment codes, the PPVs are lower and cautious use is warranted. However, the DNPR remains a valuable tool for future observational research on hypospadias.

Purpose: The Danish National Health registers provide a valuable data source that offers unique opportunities for observational research, including studies on the congenital anomaly hypospadias. The accuracy of the diagnosis and surgical treatment registration of hypospadias in the Danish National Patient Register (DNPR) remains unknown. Patients and methods: We randomly sampled 500 patients diagnosed with hypospadias in the DNPR from January 1, 1995 to December 31, 2012. Among these, 384 patients were also registered with surgical treatment for hypospadias. Medical records were collected and reviewed independently by two investigators. Any classification disagreements were resolved by consensus. Using the medical records as the gold standard, we estimated positive predictive values (PPVs) with 95% confidence intervals (CIs) for the hypospadias diagnoses and surgical treatment registrations overall, as well as for the clinical subtypes. Results: We were able to retrieve medical records for 463 (92.6%) patients with hypospadias diagnoses and for 329 (85.7%) patients registered with surgical treatment. Presence of hypospadias was confirmed in 450 of 463 patients, yielding an overall PPV (95% CI) of 97.6% (95.8%–98.7%). For subtypes of hypospadias, the PPVs ranged between 37.5% and 72.7%. For surgical treatment of hypospadias, the overall PPV was 99.7% (97.9%–99.9%). Conclusion: The validity of the registration of hypospadias diagnoses as well as surgical treatment for hypospadias in the DNPR is overall very high. For the specific subtypes of hypospadias diagnoses codes and the specific surgical treatment codes, the PPVs are lower and cautious use is warranted. However, the DNPR remains a valuable tool for future observational research on hypospadias.

During the last decades, research on cognition has undergone a reformation, which is necessary to take into account when evaluating the cognitive and behavioural aspects of therapy. This reformation is due to the research programme called Embodied Cognition (EC). Although EC may have become the theoretical authority in current cognitive science, there are only sporadic examples of EC-based therapy, and no established framework. We aim to build such a framework on the aims, methods and techniques of the current third-wave of CBT. There appears to be a possibility for cross-fertilization between EC and CBT that could contribute to the development of theory and practice for both of them. We present a case-study of an EC-based model of intervention for working with self-control in cerebral palsy.We centre the results of the study and its discussion on how we should understand and work with self-control in a more general sense from both an EC and a CBT perspective.We end by elaborating the five learning objectives and present suggestions for follow-up reading

Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08 +/- 0.13 x 10(6), 1.08 +/- 0.11 x 10(5), 1.03 +/- 0.10 x 10(4), 1.02 +/- 0.09 x 10(3), 1.04 +/- 0.10 x 10(2) and 10.0 +/- 1.5 copies/mu l. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/;CRM code ERM-AD623a-f).

Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08 +/- 0.13 x 10(6), 1.08 +/- 0.11 x 10(5), 1.03 +/- 0.10 x 10(4), 1.02 +/- 0.09 x 10(3), 1.04 +/- 0.10 x 10(2) and 10.0 +/- 1.5 copies/mu l. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/;CRM code ERM-AD623a-f).

Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08 +/- 0.13 x 10(6), 1.08 +/- 0.11 x 10(5), 1.03 +/- 0.10 x 10(4), 1.02 +/- 0.09 x 10(3), 1.04 +/- 0.10 x 10(2) and 10.0 +/- 1.5 copies/mu l. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/;CRM code ERM-AD623a-f).

Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08 +/- 0.13 x 10(6), 1.08 +/- 0.11 x 10(5), 1.03 +/- 0.10 x 10(4), 1.02 +/- 0.09 x 10(3), 1.04 +/- 0.10 x 10(2) and 10.0 +/- 1.5 copies/mu l. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/;CRM code ERM-AD623a-f).

Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08 +/- 0.13 x 10(6), 1.08 +/- 0.11 x 10(5), 1.03 +/- 0.10 x 10(4), 1.02 +/- 0.09 x 10(3), 1.04 +/- 0.10 x 10(2) and 10.0 +/- 1.5 copies/mu l. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/;CRM code ERM-AD623a-f).

Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08 +/- 0.13 x 10(6), 1.08 +/- 0.11 x 10(5), 1.03 +/- 0.10 x 10(4), 1.02 +/- 0.09 x 10(3), 1.04 +/- 0.10 x 10(2) and 10.0 +/- 1.5 copies/mu l. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/;CRM code ERM-AD623a-f).