ResuméKommunerne har siden 1980’erne etableret centrale korps af støttepædagoger. Daginstitutionerne kan søge om særlig støtte fra dette korps til pædagogiske praksis. Støttepædagogernes opgaver har ændret sig fra en kompenserende indsats til det enkelte barn til en indsats, hvor støttepædagogerne hovedsagelig skal yde støtte til pædagogernes udvikling af læringsmiljøet for alle børn i institutionen. Støttepædagogerne oplever det ofte som en følsom udfordring, når de må stille spørgsmål til fagfællers pædagogiske forståelser, antagelser og lokale praksis for at understøtte udvikling af denne. Denne udfordring kalder på en særlig form for støttepædagogisk praksis. Vi anvender begreberne interaktionel ekspertise (Collins & Evans, 2007) og pædagogisk takt (van Manen, 2015) til at forstå og karakterisere den ekspertise og faglighed, der er i spil og på spil, når der skal ydes støtte til udvikling af pædagogisk praksis i dagtilbud. Artiklen er udarbejdet på baggrund af aktionsforskning i forbindelse med et aktionslæringsforløb med støttepædagoger i en større dansk kommune. AbstractFrom assistant preschool teachers to expert with pedagogical tact Since the 1980s, many Danish municipalities have been establishing centralized units of assistant pre-school teachers who provide special assistance for the pedagogical practices of pre-school institutions. The tasks of these assistant pre-school teachers have changed over time: from an originally compensatory effort targeting individual children, to primarily assisting pre-school teachers and the development of the learning environment for all children. In the endeavor of assisting the development of these learning environments, it is often perceived as a sensitive issue, when assistant pre-school teachers question the pedagogical assumptions and local practices of their professional peers. This challenge calls for a special kind of pedagogical practice. In this article, we apply the concepts of interactional expertise (Collins & Evans, 2007) and pedagogical tact (van Manen, 2015) to characterize the expertise and professionalism that is at play and at stake, in the provision of assistance for the development of pedagogical practices in pre-schools institutions. The article has been developed based on action research in connection to an action learning course for assistant pre-schools teachers in a larger Danish municipality.

ResuméMed skolereformen fra 2014 har pædagoger fået en ny rolle i skolen, hvor de bl.a. varetager ”understøttende undervisning”. Det er dog stadig ikke helt klart, hvad pædagoger kan bidrage med i skolen, og hvordan deres bidrag forholder sig til lærernes. Med denne artikel præsenterer vi, med udgangspunkt i et almenpædagogisk perspektiv, et mere udfoldet bud på, hvad pædagoger kan bidrage med i skolen, og særligt hvordan de kan bidrage til at mindske marginalisering af børn. Vi argumenterer for, at pædagoger frem for at benytte sig af tydeligt instruerede aktiviteter, der minder om lærernes undervisning, med fordel kan benytte sig af arrangementet som en pædagogisk handlingsform, hvor den pædagogiske intention bevidst holdes svag for børnene. Hermed kan pædagoger bruge deres pædagogiske faglighed til at fremme børns medvirken i egne lærings- og dannelsesprocesser samt mindske marginalisering i skole og SFO. AbstractThe Danish school reform (2014) has given pedagogues (social educators) a new role in primary schools, where they among other things provide "supportive teaching". However, it is still not quite clear how pedagogues contribute and how their contribution relates to that of the teachers. Based on a general pedagogical theoretical perspective, we propose a more detailed description of pedagogues’ contribution in the school context, with a particular focus on reducing marginalization of children. We argue that pedagogues, rather than using clearly instructed activities similar to teachers' lessons, should make use of ”the pedagogical arrangement” as a form of action, in which the pedagogues’ intention is deliberately kept subtle. In this way, pedagogues may use their pedagogical expertise to promote children's involvement in their own learning and Bildung processes and to reduce marginalization in schools and school-based leisure time facilities.

Background: For decades, tumour hypoxia has been pursued as a cancer treatment target. However, prognostic and predictive biomarkers are essential for the use of this target in the clinic. This study investigates the prognostic value of a hypoxia-induced gene profile in localised soft tissue sarcoma (STS).Methods: The hypoxia-induced gene quantification was performed by real-time quantitative PCR (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene expression cut-points were determined in a test cohort of 55 STS patients and used to allocate each patient into a more or a less hypoxic group. The cut-points found in the test cohort were applied to a cohort of 77 STS patients for validation.Results: For patients with localised high-grade STS treated with surgery with or without postoperative radiation therapy, the prognostic value of the hypoxia-induced gene profile was proved in the test cohort and confirmed in the validation cohort. After adjustment for confounders, the hazard ratio (HR) was 3.2 (95% CI: 1.5; 7.0) for patients with more hypoxic tumours compared with patients with less hypoxic tumours regarding disease-specific survival. Moreover, for the development of metastatic disease, the HR was 2.61 (95% CI: 1.27; 5.33).Conclusions: The hypoxia-induced gene profile is a validated independent prognostic marker that may help identify STS patients needing more aggressive or different adjuvant treatment.

Yield and nitrogen (N) use efficiency (NUE) are important traits for the evaluation of crops used for renewable energy production. Contrary to other bio-energy crops, data on NUE are not available for beet crops from the Beta genus for high yielding conditions of northwestern Europe. Thus, our study aimed to provide such information for one current representative of the cultivar groups sugar and fodder beet. Field experiments were conducted with six mineral fertilizer N doses (0-200 kg N ha(-1), 40 kg steps) at one site in Germany (DE), The Netherlands (NL) and Denmark (DK) in 2010 and 2011; each combination of site and year (DE10, DE11, NL10, NL11, DK10, DK11) was evaluated as distinct environment.The environments strongly differed in yield (dry matter, sugar), N uptake, harvest indices and N utilization efficiency (NUtE) parameters. Increasing the fertilizer N dose increased dry matter yield and sugar yield in the environments NL10, NL11, DK10 and DK11, but not at DEW and DE11. Harvest indices decreased with increasing fertilizer N dose in the environments NL10, NL11, DK10 and DK11 only, which were characterized by a 70-110 kg N ha(-1) lower N uptake at zero fertilizer N than DE10 and DE11. The N uptake continuously increased while NUtE decreased with increasing fertilizer N dose at all environments. When regarding environmental and fertilizer N effects, yield was neither related to harvest indices nor NUtE.Despite several significant interactions between environment and cultivar, the data clearly reveal that yield, sucrose concentration in taproot dry matter, total plant N uptake, NUtE and apparent fertilizer N recovery were considerably higher for sugar beet (SB) than for fodder beet (FB). Contrastingly, harvest index on taproot dry matter basis and N harvest index were higher in FB than in SB, while harvest index for sugar was similar. An improved harvest index was obviously not the cause for the higher sugar yield of SB compared to FB, while sucrose concentration in taproot dry matter was clearly favourable for SB. Although SB crops incorporated more N into the leaves than FB, NUtE was considerably higher in SB, especially when focusing on sugar instead of dry matter production. In conclusion, SB offers a higher potential for producing bio-energy per unit of arable land with less N use related greenhouse gas emissions per unit of energy gain than FB. (C) 2015 Elsevier B.V. All rights reserved.

BACKGROUND:Treatment of high-grade osteosarcoma remains a major challenge in orthopedic oncology as no major breakthrough in overall survival has occurred in the past 20 years. Due to the rarity of the disease, comparing the results of a single institution to best standard practice needs the establishment of clinical databases. The aim of this study was to report the cumulative 30-years' experience of a single institution and to assess the incidence, survival and prognostic factors of high-grade osteosarcoma using a recently validated, hospital-based database, representing all citizens living in western Denmark, the Aarhus Sarcoma Registry.MATERIAL AND METHODS:Between 1979 and 2008, 169 patients were treated at the Sarcoma Centre of Aarhus University Hospital for high-grade osteosarcoma. The incidence was calculated as a WHO age-standardized incidence per million per year. The endpoint was overall survival, analyzed by the Kaplan-Meier method and log-rank. Possible prognostic factors were analyzed by the uni- and multivariate Cox proportional hazard method.RESULTS:The incidence of high-grade osteosarcoma in western Denmark from 1979 to 2008 was 2.7/million inhabitants/year. The five-year overall survival was 42% (95% CI 34; 49) for the whole cohort of patients with high-grade osteosarcoma and 54% (95% CI 43; 64) for patients with localized disease treated with wide excision and chemotherapy. For patients treated with curative intent, no soft tissue extension, treatment with sufficient surgical margin and standard chemotherapy, as well as a high degree of necrosis after chemotherapy were all independent prognostic factors for overall survival.CONCLUSION:The data from this hospital-based, validated database confirms the relevance of the known prognostic factors of high-grade osteosarcoma and emphasizes the importance of adequate surgical margins and chemotherapy.

BACKGROUND The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). METHODS We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. RESULTS Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. CONCLUSION Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.

OBJECTIVE:Reverse transcription quantitative real-time polymerase chain reaction is efficient for quantification of gene expression, but the choice of reference genes is of paramount importance as it is essential for correct interpretation of data. This is complicated by the fact that the materials often available are routinely collected formalin-fixed, paraffin-embedded (FFPE) samples in which the mRNA is known to be highly degraded. The purpose of this study was to investigate 22 potential reference genes in sarcoma FFPE samples and to study the variation in expression level within different samples taken from the same tumor and between different histologic types.METHODS:Twenty-nine patients treated for sarcoma were enrolled. The samples encompassed 82 (FFPE) specimens. Extraction of total RNA from 7-μm FFPE sections was performed using a fully automated, bead-base RNA isolation procedure, and 22 potential reference genes were analyzed by reverse transcription quantitative real-time polymerase chain reaction. The stability of the genes was analyzed by RealTime Statminer. The intrasamples variation and the interclass correlation coefficients were calculated. The linear regression model was used to calculate the degradation of the mRNA over time.RESULTS:The quality of RNA was sufficient for analysis in 84% of the samples. Recommended reference genes differed with histologic types. However, PPIA, SF3A1, and MRPL19 were stably expressed regardless of the histologic type included. The variation in ∆Cq value for samples from the same patients was similar to the variation between patients. It was possible to compensate for the time-dependent degradation of the mRNA when normalization was made using the selected reference genes.CONCLUSION:PPIA, SF3A1, and MRPL19 are suitable reference genes for normalization in gene expression studies of FFPE samples from sarcoma regardless of the histology.

Irradiation is a major causative factor among the small subgroup of sarcomas with a known etiology. The prognosis of radiation‐induced sarcomas (RIS) is significantly worse than that of their spontaneous counterparts. The most frequent histological subtypes include undifferentiated pleomorphic sarcomas, angiosarcomas, and leiomyosarcomas. A high frequency of MYC amplifications in radiation‐induced angiosarcomas, but not in primary angiosarcomas, has recently been described. To investigate whether MYC amplifications are also frequent in RIS other than angiosarcomas, we analyzed the MYC amplification status of 83 RIS and 192 sporadic sarcomas by fluorescence in situ hybridization. We found significantly higher numbers of MYC amplifications in RIS than in sporadic sarcomas ( P < 0.0001), especially in angiosarcomas, undifferentiated pleomorphic sarcomas, and leiomyosarcomas. Angiosarcomas were special in that MYC amplifications were particularly frequent and always high level, while other RIS showed low‐level amplifications. We conclude that MYC amplifications are a frequent feature of RIS as a group and may contribute to the biology of these tumors. © 2012 Wiley Periodicals, Inc.

Treatment with tyrosine kinase inhibitors (TKIs) has drastically improved overall survival (OS) of patients with advanced GIST. The aim of this study is to evaluate the results of treatment with different TKIs on advanced GIST and identify prognostic factors for OS. The medical records of all patients treated at the Department of Oncology, Aarhus University Hospital were retrospectively reviewed. Between 2001 and 2009, 80 patients with advanced GIST were treated with imatinib as first-line therapy. The median OS was 44 months (95% CI 31–56), and the 5-year OS was 40%. Since 2005, 32 patients were treated with sunitinib as 2nd-line therapy. The median time to progression was 9 months (95% CI: 3–13 months), and the 3-year OS was 30%. The data illustrate that data from large multicenter studies are reproducible in a single sarcoma centre. This retrospective study pointed to low serum sodium at the start of imatinib as a possible prognostic factor affecting OS.

Aim of study. The primary aim of this study was to evaluate the effect of half-body irradiation (HBI) on pain and quality of life in cancer patients with multiple bone metastases. The secondary aim was to evaluate side effects of the treatment. Patients and methods. A total of 44 patients received lower (n = 37), upper (n = 5), or sequential HBI (n = 2). The dose for lower HBI was 8 Gy in one fraction and for upper HBI 7 Gy in one fraction, with reduction of the lung dose to 6 Gy in one fraction by partial shielding. The majority of patients (n = 41) were males with prostate cancers (93%). Outcome and side effects were measured by the EORTC Quality of Life Questionnaire C30 (QLQ-C30), and by the doctors' toxicity scores in the medical record. Pain relief was defined as a reduction of more than 10 points on the QLQ-C30 scale. Evaluations were performed before and 2, 4, 8, 16, and 24 weeks after treatment. Results. Relief of pain was observed in 76% of the patients receiving HBI with 8.8% of the patients experiencing complete pain relief with no residual pain in the treated field. For most patients, the pain relief was lasting throughout the follow-up period. About one third of the patients were able to reduce their intake of analgesics. Grade 1-2 diarrhoea was the most common side effect observed in 49% of the patients two weeks after treatment. Mild pulmonary symptoms (grade 1-2) were observed in four of seven patients receiving upper HBI. No clear effect was observed on the patients' global quality of life.Conclusion. Single fraction HBI is safe and effective providing long lasting pain reduction in 76% of patients with multiple bone metastases.

The YSNSG peptide is a synthetic peptide targeting αvβ3 integrin. This peptide exhibits promising activity in vitro and in vivo against melanoma. To determine pharmacokinetic parameters and predictive active doses in the central nervous system (CNS) and subcutaneous tissue (SC), we conducted microdialysis coupled with pharmacokinetic modeling and Monte Carlo simulation. After a recovery period of surgical procedures, a microdialysis probe was inserted in the caudate and in subcutaneous tissue. Plasma samples and dialysates collected 5 h after YSNSG intravenous administration (10 mg/kg) were analyzed by UPLC-MS/MS. A nonlinear mixed-effect modeling approach implemented in Monolix® 2016R1 was performed. Model selection and evaluation were based on the usual diagnostic plot, precision and information criteria. The primary plasma and tissue pharmacokinetic parameters were comparable with those of other integrin antagonists, such as cilengitide or ATN-161. Tissue/plasma and brain/plasma area under the curve (AUC) ratio were 66.2 ± 21.6% and 3.6 ± 4.7%, respectively. Two models of 2-compartments with an additional microdialysis compartment, parameterized as rate constants (k for elimination, k12/k21 and k13/k31 for distribution) and volumes (central V1 and peripheral microdialysis compartment V3) with zero-order input were selected to describe the dialysate concentrations in CNS and SC. The inter-individual variability (IIV) was described by exponential terms, and residual variability was described by a combined additive and proportional error model. Individual AUC (plasma and tissues) values were derived for each animal using the Empirical-Bayes-Estimates of the individual parameters. The regimens needed to achieve an in vitro predetermined target concentration in tissues were studied by Monte Carlo simulations using Monolix® 2016R1. YSNSG pharmacokinetic parameters show promising results in terms of subcutaneous disposition. Further investigations into such processes as encapsulation and intratumoral disposition are currently being conducted.

No standard treatment is established for patients with advanced soft tissue sarcoma after previous chemotherapy with anthracyclines and ifosfamide, given either in combination or sequentially. Exatecan (DX-8951f) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself, topotecan or irinotecan. Since some activity against soft tissue sarcomas, especially leiomyosarcomas, has been reported for topoisomerase I-inhibitors, a study with a new and more potent agent seemed justified.We report on a prospective multicentre phase II study of Exatecan in adult soft tissue sarcomas failing I or 2 lines of chemotherapy in advanced phase, performed within the STBSG of EORTC. Thirty-nine patients (16 leiomyosarcomas and 23 other histologies) were included in two independent strata and received a total of 141 cycles (median 2). Median age was 61 years, range 25-76. Exatecan was given as i.v. infusion over 30 min at a dose of 0.5 mg/m(2) every day for five consecutive days, repeated every 21 days. Seventy-four percentage of cycles could be given without dose Or schedule modification. The main toxicity was haematotoxicity with grade 3/4 neutropenia in 49%, grade 3/4 thrombocytopenia in 23%, and grade 3/4 anaemia in 15% of patient:3, respectively. Non-haematological toxicity consisted mainly of grade 2/3 dyspnoea in 36% of patients and grade 2/3 fatigue in 28%. One treatment-related toxic death due to septic shock was reported. Best overall response was no change with 60% in the leiomyosarcoma group and 53% in the non-leiomysarcoma group, respectively The 3 months progression-free survival estimates are 56% for leiomysarcomas and 26% for other histologies, respectively Using a two-step statistical design, the trial was stopped after the first step in both strata, due to lack of activity.In pretreated soft tissue sarcoma patients, Exatecan is well tolerated but does not achieve any objective responses. However, with respect to progression-free survival, Exatecan did show some activity in leiomyosarcomas. (C) 2007 Elsevier Ltd. All rights reserved.

To investigate the histological features of foci, which showed signal intensities different from fat by magnetic resonance (MR) imagings in well-differentiated lipoma-like liposarcomas and a case of lipoma, a retrospective review of these lipomatous tumors was performed to correlate MR and histological findings. Microscopic findings revealed that these foci were also composed of lipomatous tissue. Well-differentiated liposacoma and benign lipoma associated with such foci should be differentiated from dedifferentiated liposarcoma based on the histological findings.

0P1-1 THE ACCURACY OF IMPRINT CYTOLOGY OF SENTINEL LYMPH NODE IN BREAST CANCER: AN ANALYSIS OF CAUSES OF DISCREPANCIES Peir-In Liang, Ming-Yuan Lee, Ben-Long Yu, Chii-Ming Chen, Dong-Ling You, Christopher K-J Lin 1 Department of Pathology and Laboratory Services, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan 2 Department of General Surgery, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan 3 Department of Nuclear Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan 4 Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan