Research Evaluation of the Laboratory Comparison Exercise for NO, NO2, SO2, CO and O3 Langen (D) 1st - 6th September 2013

From the 1st to the 6th of September 2013 in Langen (D), 7 Laboratories of WHO/AQUILA (Network of European Air Quality Reference Laboratories) met at a laboratory comparison exercise to evaluate their proficiency in the analysis of inorganic gaseous pollutants covered by European Directive about air quality (SO2, CO, NO, NO2 and O3). The proficiency evaluation, where each participant’s bias was compared to two criteria, provides information on the current situation and capabilities to the European Commission and can be used by participants in their quality control system. On the basis of criteria imposed by the European Commission, 75.7% of the results reported by the laboratories were good both in terms of measured values and reported uncertainties. Another 20.9% of the results had good measured values, but the reported uncertainties were too high and for 2.0% values the uncertainty was underestimated. 1.4% values were questionable. Comparability of results among participants at the highest concentration level, excluding outliers, is acceptable for NO, SO2 and O3 measurements while NO2 and CO one showed less satisfactory results.JRC.H.2-Air and Climat

Evaluation of the Laboratory Comparison Exercise for SO2, CO, O3, NO and NO2, Langen 23rd-28th October 2011

From the 23rd to the 28th of October 2011 in Langen (DE), 7 Laboratories of WHO/AQUILA (Network of European Air Quality Reference Laboratories) met at an laboratory comparison exercise to evaluate their proficiency in the analysis of inorganic gaseous pollutants covered by European Directive about air quality (SO2, CO, NO, NO2 and O3). The proficiency evaluation, where each participant’s bias was compared to two criteria, provides information on the current situation and capabilities to the European Commission and can be used by participants in their quality control system. On the basis of criteria imposed by the European Commission, 59.4% of the results reported by the laboratories were good both in terms of measured values and reported uncertainties. Another 39.9% of the results had good measured values, but the reported uncertainties were too high and only 0.7% delivered questionable results. Comparability of results among participants at the highest concentration level, excluding outliers, is acceptable for CO and NO measurements while SO2, O3 and NO2 measurements showed less satisfactory results.JRC.H.2-Air and Climat

Evaluation of the Laboratory Comparison Exercise for NO, NO2, SO2, CO and O3 4th – 9th of October 2015, Langen (D)

From the 4th to the 9th of October 2015 seven Laboratories of the World Health Organization (WHO) European-Region met for another joint JRC-ERLAP/WHO inter-laboratory comparison exercise (IE). They met at the National Air Quality Reference laboratory at the German Federal Environment Agency in Langen, Germany, to evaluate their proficiency in the analysis of inorganic gaseous pollutants (NO, NO2, SO2, CO and O3) covered by the European Air Quality Directive 2008/50 EC and recent revision 2015/1480/EC. The proficiency evaluation, where each participant’s bias was compared to two criteria, provides information on the current situation and capabilities to the European Commission and can be used by participants in their quality control system. On the basis of criteria imposed by the European Commission, 73.2% of the results reported by the laboratories were good both in terms of measured values and reported uncertainties. Another 23.9% of the results had good measured values, but the reported uncertainties were too high and for 0.7% values the uncertainty was underestimated. 1.4% values were questionable and 0.7% unsatisfactory. Comparability of results among participants (reproducibility) at the highest concentration level, excluding outliers, is acceptable for CO and SO2 measurements while NO2, NO and O3 one showed less satisfactory results.JRC.H.2-Air and Climat

The Evaluation of the Interlaboratory Comparison Exercise for SO2, O3, NO and NO2 Langen 20th-25th September 2009

From the 20th to the 25th of September 2009 in Langen (DE), 4 national reference laboratories (NRL) of AQUILA network and 3 laboratories of the World Health Organisation (WHO) Euro-Region met for an interlaboratory comparison exercise (IE) to evaluate their proficiency in the analysis of inorganic gaseous pollutants covered by European Air Quality Directives (SO2, NO, NO2 and O3). Most of the laboratories participating in the IE used automated CEN reference methods, which are mandatory in the EU, while some laboratories of the WHO Euro-Region performed analysis using manual methods. In this report proficiency evaluation was made at different degrees for each laboratory taking into account the differences in the methodologies and the completeness of the information provided by participants. For the laboratories who expressed their uncertainty, performance was evaluated using two criteria, providing information on their proficiency to the European Commission and supporting the national quality control systems. In terms of criteria imposed by the European Commission (that are not mandatory for WHO laboratories), 71% of the results reported by National Reference Laboratories (AQUILA network) were good both in terms of measured values and reported uncertainties. Another 23% of the results had good measured values, but the reported uncertainties were either too high (19%) or too small (4%). There were no questionable nor unacceptable values. AQUILA laboratories presented good comparability among participants for NO2, O3, and SO2. The relative reproducibility limit for NO was above the objective deriving from the standard deviation for proficiency assessment. For WHO laboratories using automated techniques, the results are satisfactory for SO2, NO2 and NO measurement methods, while one laboratory needs further investigation of their O3 measurements. The laboratory using manual methods presented results comparable to those of the automated methods for NO and O3 but there were questionable results for NO2 and SO2 and unsatisfactory results for NO2.JRC.DDG.H.4-Transport and air qualit

Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme

Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 × 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan–Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6–16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma

5-ALA Fluorescence in Native Pituitary Adenoma Cell Lines: Resection Control and Basis for Photodynamic Therapy (PDT)?

<div><p>Objective: Pituitary adenomas (PA), especially invasive ones, are often not completely resectable. Usage of 5-aminolevulinic acid (5-ALA) for fluorescence guided surgery could improve the rate of total resection and, additionally, open the doors for photodynamic therapy (PDT) in case of unresectable or partially resected PAs. The aim of this study was to investigate the uptake of 5-ALA and the effect of 5-ALA based PDT in cell lines. Methods: GH3 and AtT-20 cell lines were incubated with different concentrations of 5-ALA, protoporphyrin IX (PPIX) fluorescence was measured by flow cytometry and fluorescencespectrometry. WST-1 assays were performed to determine the surviving fraction of cells after PDT. PPIX fluorescence intensities and PDT effect of the pituitary adenoma cells were compared to U373MG, a well-known glioblastoma cell line. Results: Both cell lines showed a 5-ALA dependent intracellular PPIX fluorescence. Significant differences after 24hrs of incubation were observed in AtT-20 cells in comparison to GH3. Regardless of the incubation or metabolism time, there was a proliferation inhibiting effect after PDT, with no statistical significance. Conclusion: Since GH3 cells showed a heterogenous uptake of 5-ALA in the flow cytometry profile, but not constantly high concentrations they might have a 5-ALA efflux mechanism, which still needs to be determined. In the case of AtT-20, the cells might need a longer time for the uptake due to their size or slow metabolism. We showed that the different cell lines have different uptake and metabolism mechanisms, which needs to be further investigated. The general uptake of 5-ALA allows the possibility of resection control and PDT for pituitary adenomas. But, the role of PDT for unresectable pituitary adenomas deserves further investigations.</p></div

Protoporphyrin IX (PpIX) Fluorescence during Meningioma Surgery: Correlations with Histological Findings and Expression of Heme Pathway Molecules

Background: The usefulness of 5-ALA-mediated fluorescence-guided resection (FGR) in meningiomas is controversial, and information on the molecular background of fluorescence is sparse. Methods: Specimens obtained during 44 FGRs of intracranial meningiomas were analyzed for the presence of tumor tissue and fluorescence. Protein/mRNA expression of key transmembrane transporters/enzymes involved in PpIX metabolism (ABCB6, ABCG2, FECH, CPOX) were investigated using immunohistochemistry/qPCR. Results: Intraoperative fluorescence was observed in 70 of 111 specimens (63%). No correlation was found between fluorescence and the WHO grade (p = 0.403). FGR enabled the identification of neoplastic tissue (sensitivity 84%, specificity 67%, positive and negative predictive value of 86% and 63%, respectively, AUC: 0.75, p p p = 0.351). Protein expression of ABCB6, ABCG2, FECH and CPOX was found in meningioma tissue and was correlated with fluorescence (p < 0.05, each), whereas this was not confirmed for mRNA expression. Aberrant expression was observed in the CNS. Conclusion: FGR enables the intraoperative identification of meningioma tissue with limitations concerning dura invasion and due to ectopic expression in the CNS. ABCB6, ABCG2, FECH and CPOX are expressed in meningioma tissue and are related to fluorescence

Flow cytometry data of PPIX fluorescence in pituitary adenoma cells.

<p>(A) The pituitary adenoma cell lines GH3 and AtT-20 were incubated for 6 and 24hrs with 100 g/ml 5-ALA (black line) or with media alone (gray area). One out of 3–7 independent experiments is shown. (B andC) MFI of all flow cytometry experiments are shown. Error bars represent S.E.M.</p

Multimodal Imaging of Patients With Gliomas Confirms C-11-MET PET as a Complementary Marker to MRI for Noninvasive Tumor Grading and Intraindividual Follow-Up After Therapy

The value of combined L-(methyl-[(11) C]) methionine positron-emitting tomography (MET-PET) and magnetic resonance imaging (MRI) with regard to tumor extent, entity prediction, and therapy effects in clinical routine in patients with suspicion of a brain tumor was investigated. In n = 65 patients with histologically verified brain lesions n = 70 MET-PET andMRI (T1-weighted gadolinium-enhanced [T1w-Gd] and fluid-attenuated inversion recovery or T2-weighted [FLAIR/T2w]) examinations were performed. The computer software visualization and analysis framework volume rendering engine (Voreen)'' was used for analysis of extent and intersection of tumor compartments. Binary logistic regressionmodelswere developed to differentiate betweenWorldHealthOrganization (WHO) tumor types/grades. Tumor sizes as defined by thresholding based on tumor-to-background ratios were significantly different as determined byMET-PET (21.6 +/- 36.8 cm(3)), T1w-Gd-MRI (3.9 +/- 7.8 cm(3)), and FLAIR/T2-MRI (64.8 +/- 60.4 cm(3); P < .001). TheMETPET visualized tumor activity whereMRI parameterswere negative: PET positive tumor volumewithout Gd enhancementwas 19.8 +/- 35.0 cm(3) and without changes in FLAIR/T2 10.3 +/- 25.7 cm(3). FLAIR/T2-MRI visualized greatest tumor extentwith differences toMETPET being greater in posttherapy (64.6 +/- 62.7 cm(3)) than in newly diagnosed patients (20.5 +/- 52.6 cm(3)). The binary logistic regression model differentiated betweenWHOtumor types (fibrillary astrocytoma II n - 10 fromother gliomas n - 16) with an accuracy of 80.8% in patients at primary diagnosis. Combined PET and MRI improve the evaluation of tumor activity, extent, type/grade prediction, and therapy-induced changes in patients with glioma and serve information highly relevant for diagnosis and management