Experimentelle Methoden in der Mikroökonomik

Series: Department of Economics Working Paper Serie

Der öffentliche Sektor aus ordnungspolitischer Sicht

Series: Department of Economics Working Paper Serie

Evaluation of the new Asp ID polymerase chain reaction assay for detection of Aspergillus species: A pilot study

The newly developed AspID PCR assay for detection of Aspergillus spp. was evaluated with an interlaboratory quality control programme panel and human bronchoalveolar lavage fluid (BALF) samples. With the quality control programme, 8 out of 9 panel members were correctly identified. With the clinical study, 36 BALF samples that had been obtained from 18 patients with invasive pulmonary aspergillosis (IPA) and 18 without IPA were investigated. Sensitivity, specificity, positive and negative likelihood ratio for the AspID assay were 94.1% (95% CI 73.3-99.9), 76.5% (95% CI 50.1-93.2), 4 (95% CI 1.7-9.5) and 0.1 (95% CI 0.01-0.5) respectively

Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.

Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection

Clinical Evaluation of the Newly Formatted Lateral-Flow Device for Invasive Pulmonary Aspergillosis

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The study evaluated the newly formatted Aspergillus-specific lateral-flow-device (LFD), and compared its performance to the original prototype “old” LFD test using BALF samples from 28 patients (14 patients with probable/proven invasive pulmonary aspergillosis [IPA] and 14 patients with no evidence for IPA). A total of 10/14 (71%) of BALF samples from patients with probable/proven IPA resulted positive with the new LFD, including 8/9 with true-positive and 2/5 with false-negative results with the old LFD. All 14 samples from patients without IPA resulted negative with the new LFD; specificity of the new LFD was significantly improved compared to the old LFD.This work was supported by funds of the Oesterreichische Nationalbank (Anniversary Fund, project number 15346) and the Gilead Investigator Initiated Study IN-AT-131-1939. This work has also partly been carried out with the K1 COMET Competence Center CBmed, which is funded by the Federal Ministry of Transport, Innovation and Technology (BMVIT); the Federal Ministry of Science, Research and Economy (BMWFW); Land Steiermark (Department 12, Business and Innovation); the Styrian Business Promotion Agency (SFG); and the Vienna Business Agency. The COMET program is executed by the FFG (The Austrian Research Promotion Agency, project number 844609). LFD tests used in this study were provided by OLM Diagnostics. The funders had no role in study design, data collection, analysis, interpretation, decision to publish, in the writing of the manuscript, and in the decision to submit the manuscript for publication

Multicenter evaluation of a lateral-flow device test for diagnosing invasive pulmonary aspergillosis in ICU patients.

Published onlineClinical TrialJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tINTRODUCTION: The incidence of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is increasing, and early diagnosis of the disease and treatment with antifungal drugs is critical for patient survival. Serum biomarker tests for IPA typically give false-negative results in non-neutropenic patients, and galactomannan (GM) detection, the preferred diagnostic test for IPA using bronchoalveolar lavage (BAL), is often not readily available. Novel approaches to IPA detection in ICU patients are needed. In this multicenter study, we evaluated the performance of an Aspergillus lateral-flow device (LFD) test for BAL IPA detection in critically ill patients. METHODS: A total of 149 BAL samples from 133 ICU patients were included in this semiprospective study. Participating centers were the medical university hospitals of Graz, Vienna and Innsbruck in Austria and the University Hospital of Mannheim, Germany. Fungal infections were classified according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: Two patients (four BALs) had proven IPA, fourteen patients (sixteen BALs) had probable IPA, twenty patients (twenty-one BALs) had possible IPA and ninety-seven patients (one hundred eight BALs) did not fulfill IPA criteria. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratios for diagnosing proven and probable IPA using LFD tests of BAL were 80%, 81%, 96%, 44% and 17.6, respectively. Fungal BAL culture exhibited a sensitivity of 50% and a specificity of 85%. CONCLUSION: LFD tests of BAL showed promising results for IPA diagnosis in ICU patients. Furthermore, the LFD test can be performed easily and provides rapid results. Therefore, it may be a reliable alternative for IPA diagnosis in ICU patients if GM results are not rapidly available. TRIAL REGISTRATION: ClinicalTrials.gov NCT02058316. Registered 20 January 2014.PfizerOesterreichische Nationalbank (Anniversary Fund, project number 15346)

太平洋におけるアクチノイドの海水循環トレーサーとしての利用

内容の要約広島大学(Hiroshima University)博士(理学)Doctor of Sciencedoctora

Determination of 236U, 238U and 234U isotopes and the 240Pu/239Pu ratio in water samples

Im Rahmen dieser Diplomarbeit wurden die Isotopenverhältnisse von 239Pu/240Pu und 236U/238U sowie der Gehalt der Radionuklide 234U und 238U in verschiedenen Gewässern analysiert. Dafür wurde zuerst eine geeignete Probenvorbereitung gesucht. Zu diesem Zweck wurden drei verschiedene Methoden an Leitungswasser, Wasser aus einem Bergwerk und künstlichem Meerwasser ausprobiert. Dabei wurde ein 232U spike verwendet und verschiedene Harze wurden zur Abtrennung des Urans getestet. Nach einer Mikropräzipitation mit NdF3 wurde der Gehalt an Uran mittels Alphaspektrometrie bestimmt. Die Probenvorbereitung, die sich als am besten geeignet für Meerwasserproben erwiesen hat, basiert auf der Mitfällung des Urans mit Fe(OH)3. Diese Methode wurde dann als Ausgangspunkt für zwei weitere Tests verwendet, in denen zwei verschiedene Trenntechniken für Uran und Plutonium (unter Verwendung eines 242Pu spikes) getestet wurden. Für die gleichzeitige Bestimmung dieser beiden Elemente wurde eine Methode gewählt, bei der Plutonium mit einem Dowex® 1x8 Harz und Uran im Anschluss daran mittels UTEVA® Harz separiert wird. Die Wasserproben wurden verschiedenen Flüssen und Ozeanen entnommen. Die Isotopenverhältnisse 239Pu/240Pu bzw. 236U/238U wurden mittels Beschleunigungsmassenspektrometrie (AMS) ermittelt, während Alphaspektrometrie für die Bestimmung der Aktivitätskonzentrationen von 234U und 238U herangezogen wurde. Bei der Analyse der Ergebnisse wurde festgestellt, dass alle Proben durch die nukleare Aktivität des Menschen der letzten Jahrzehnte beeinflusst waren. Die Isotopenverhältnisse zeigen Werte, wie sie für den globalen Fallout üblich sind, mit Ausnahme der Probe des Wassers aus der Irischen See, welche eindeutig den Einfluss der Wiederaufbearbeitungsanlage in Sellafield zeigt.In the course of this diploma thesis, water samples from rivers and oceans were analyzed regarding their content of 234U and 238U and their 236U/238U and 240Pu/239Pu ratios. In the beginning, a suitable method for the separation of uranium and plutonium from large water samples had to be found. For this purpose, three different methods were tested on tap water, mine water and artificial sea water. In those preliminary tests, a 232U spike solution was used and uranium was separated by different resins. Then uranium was co-precipitated with NdF3 and measured by alpha-spectrometry. A sample preparation method using Fe(OH)3 co-precipitation proved to be most efficient and was best suited for the handling of sea water samples. Based on this method, two different separation procedures for the combined extraction of uranium and plutonium (using 242Pu spike solution) were tested. The sample preparation method which was finally chosen consists of separating plutonium by Dowex® 1x8 resin, followed by uranium extraction using UTEVA® resin. The river and sea water samples were collected from different places around the world. The 236U/238U and 239Pu/240Pu isotopic ratios were measured by accelerator mass spectrometry (AMS), whereas the 234U and 238U activity concentrations were assessed by alpha-spectrometry. All samples seem to be affected by the nuclear activity of mankind. The water samples show typical values ascertained for global fallout, with the exception of water from the Irish Sea, which was clearly influenced by the reprocessing plant in Sellafield, UK

Point of Care Testing for the Diagnosis of Fungal Infections: Are We There Yet?

Diagnostic tools for invasive fungal infections have continuously improved within the last decades. Nowadays, cultural methods, antigen testing, and molecular tests, such as polymerase chain reaction, are widely used. These methods, however, are accompanied with different limitations as various availability, various turnaround time or high costs. A new generation of point-of-care test has shown promising results in various studies and may overcome some of these limitations. We therefore reviewed the literature for the most promising new point-of-care tests for invasive aspergillosis (Aspergillus-specific lateral-flow device test, Aspergillus proximity ligation antigen assay), cryptococcosis (cryptococcal lateral-flow assay), and for histoplasmosis (loop-mediated isothermal amplification assay)