Measuring Synchronicity and Co-movement of Business Cycles with an Application to the Euro Area

We develop multivariate measures of synchronicity and co-movement of business cycles. In addition to synchronicity, the co-movement measure takes differences between cycle amplitudes into account that have been overlooked in most previous studies. We apply the new measures to the euro area. Synchronicity and co-movement for the region as a whole do not exhibit a clear upward tendency. Although several countries saw the similarity of their business cycle vis-`a-vis the euro area reference cycle increase, national business cycles remain fairly diverse. Changes in business cycle amplitudes cause most of the observed change in cycle co-movement.business cycles, synchronisation, concordance, co-movement, cycle amplitudes, euro area

Klinische und histopathologische Charakterisierung des Peniskarzinoms unter Berücksichtigung des HPV-Status

Das Peniskarzinom ist eine seltene Tumorerkrankung des Mannes mit einer Häufung in der 5. und 6. Lebensdekade. Aufgrund der Seltenheit der Erkrankung basieren die meisten Daten über Prognosefaktoren des Peniskarzinoms auf kleinen Kohorten und einer geringen Anzahl an Studien. Entsprechend fehlen nach wie vor Prognoseparameter mit ausreichender Evidenz für die klinische Entscheidungsfindung. So wird die prognostische Wertigkeit der HPV-Infektion, die bei ca. 50% der Peniskarzinome vorliegt, kontrovers diskutiert. Ziel dieser retrospektiven multizentrischen Studie war die Evaluation klinisch relevanter Parameter zur Prognosedifferenzierung und eine Evaluation der aktuellen TNM-Klassifikation hinsichtlich ihrer Prognoseabschätzung. Insgesamt wurden klinische Daten und Gewebeproben von 276 Patienten mit Peniskarzinom zwischen 1989 und 2018 aus Deutschland, Russland und Portugal gesammelt und ausgewertet mit Bestimmung des HPV- und p16-Status, sowie des histologischen Subtyps. Das mediane Alter in der Kohorte lag bei 63 Jahren, bei 23,55% der Patienten bestand eine HPV-assoziierte Tumorentstehung. In der multivariaten Analyse war pN2-3 signifikant mit einem geringeren metastasenfreien, tumorspezifischen und Gesamtüberleben assoziiert (p = <0,001). Die lymphovaskuläre Infiltration war ein signifikanter Parameter für das tumorspezifische (p = 0,005) und Gesamtüberleben (p = 0,007), aber nicht für das metastasenfreie Überleben (p = 0,346). In Bezug auf das T-Stadium war das metastasenfreie Überleben nur zwischen pT1b und pT1a signifikant unterschiedlich (p = 0,017), während für die T-Stadien kein Unterschied im tumorspezifischen und Gesamtüberleben gefunden wurde. pT1b-Tumoren waren mit einem schlechteren metastasenfreien, tumorspezifischen und Gesamtüberleben im Vergleich zu pT2 assoziiert. Das Grading und die perineurale Invasion zeigten in der univariaten, aber nicht in der multivariablen Analyse einen statistisch signifikanten Unterschied für das tumorspezifische und Gesamtüberleben. Bei nodal-negativen Patienten war die lymphovaskuläre Infiltration ein signifikanter unabhängiger prognostischer Parameter für ein kürzeres metastasenfreies Überleben (p = 0,032). Weder in der Gesamtkohorte, noch beim usual type alleine ergab sich ein Zusammenhang zwischen dem HPV-Status und der Prognose. Histologische Subtypen zeigten ebenfalls einen Einfluss auf die Prognose des Peniskarzinoms, jedoch ohne statistische Signifikanz. Eine lymphatische Beteiligung ist der wichtigste prognostische Parameter des Peniskarzinoms. Die schlechte Prognose im pT1b-Stadium scheint auf den Einschluss der lymphovaskulären Infiltration zur Stadieneinteilung zurückzuführen zu sein. Da die Lymphgefäßinfiltration ein unabhängiger prognostischer Parameter ist, erscheint die Stadieneinteilung des pT1b-Stadiums fragwürdig. Der histologische Subtyp sollte immer bestimmt werden, während der HPV-Status alleine von geringer klinischer Relevanz zu sein scheint. Nodal-negative Patienten mit Lymphgefäßinfiltration haben ein höheres Metastasierungsrisiko. Dies sollte als wichtiger Faktor für eine engmaschige Nachsorge und eine adjuvante Therapie berücksichtigt werden.Summary - Penile cancer is a rare malignant tumor in men with the highest incidence in the 5th and 6th life decade. Due to the rarity of the disease, most data on prognostic factors for penile cancer are based on small cohorts and a small number of studies. Accordingly, there is still a lack of prognostic parameters with sufficient evidence for clinical decision-making. The prognostic value of HPV infection, which is present in about 50% of penile carcinomas, is discussed controversially. The aim of this retrospective multicenter study was the evaluation of clinically relevant parameters for the differentiation of prognosis and the evaluation of the current TNM classification with regard to its prognostic value. Overall, clinical data and tissue samples from 276 patients with penile carcinoma from Germany, Russia and Portugal treated between 1989 and 2018 were collected and evaluated including determination of the HPV and p16 status, as well as the histological subtype. The median age in the cohort was 63 years, 23.55% of the patients had HPV-associated tumors. In multivariate analysis, pN2-3 was significantly associated with lower metastasis-free, tumor-specific, and overall survival (p = <0.001). Lymphovascular infiltration was a significant parameter for tumor-specific (p=0.005) and overall survival (p = 0.007) but not for metastasis-free survival (p = 0.346). Regarding T-stage, metastasis-free survival was significantly different only between pT1b and pT1a (p = 0.017), while no difference in tumor-specific and overall survival was found for T-stage. pT1b tumors were associated with poorer metastasis-free, tumor-specific, and overall survival compared to pT2. Grading and perineural invasion showed a statistically significant difference for tumor-specific and overall survival in univariate but not in multivariate analysis. In node-negative patients, lymphovascular infiltration was a significant independent prognostic parameter for shorter metastasis-free survival (p = 0.032). A correlation between the HPV status and the prognosis was neither found in the total cohort nor in the usual type alone. Histological subtypes also showed an influence on the prognosis of penile carcinoma, but without statistical significance. Lymphatic involvement is the most important prognostic parameter in penile cancer. The poor prognosis in the pT1b stage seems to be due to the inclusion of lymphovascular infiltration into the staging system. Since lymphovascular infiltration is an independent prognostic parameter, the staging of the pT1b stage seems questionable. The histological subtype should always be determined, while the HPV status alone seems to be of only minor clinical relevance. Nodal-negative patients with lymphatic infiltration have a higher risk of metastasis. This should be considered as an important factor for a close follow-up and adjuvant therapy

On-Line Biosensor to Detect Genotoxic Compounds in Surface Water Using a 3D-Printed Microbioreactor

The quality of safe and clean drinking water is becoming more important. Therefore, harmful pollutants in the surface and ground water need to be detected before drinking water is prepared from this. With the current methods, it is not possible to continuously monitor the intake water for the presence of genotoxic compounds (Woutersen, 2013). Therefore, a new monitor system is developed to detect the genotoxic compounds in surface water before this water is used to prepare drinking water. In this study, a biosensor is used to detect genotoxic compounds in water by recA controlled expression of the lux gene cluster in Escherichia coli strain DPD2794. This is done by continuously testing the surface water in a 3D-printed bioreactor with a working volume of 16 mL. Surface water is continuously added to a small chemostat using a ceramic hollow fiber. The ceramic hollow fiber is placed inside the bioreactor and the water with the genotoxic compounds is pushed through the wall of the hollow fiber from the inside by a syringe pump. Organisms and bigger particles flow through the tube. The water which is pushed through the wall of the hollow fiber goes directly into the bacteria culture in the bioreactor. In this way, organisms in the surface water cannot contaminate the bacteria culture. The bacteria culture is continuously pumped from the bioreactor to a 3D-printed flow cell placed in a dark cabin and back to the bioreactor. The presence of genotoxic compounds in water leads to the expression of the lux genes and the luminescence is detected with a photomultiplier placed above the flow cell. Currently the biosensor responds to nalidixic acid with a minimum concentration of 1 mg/L and several biological and physical options are investigated to obtain a higher sensitivity. When the concentration of naladixic acid decreases the lux genes are not induced anymore the luminescence fades out and the biosensor is ready to register the next event. The bioreactor consists of three 3D-printed parts and the flowcell is printed as a one piece. The 3Dprinting is performed with the stereolithography technique (SLA) using the Form 1 (Formlabs Inc., USA) with their optimized transparent resin. The biosensor requires only low and simple maintenance. Replacing fresh medium and discarding the culture waste is required to keep the system running for at least 30 days. This study showed an improved design of a biosensor for detecting genotoxic compounds using the stereolithography 3D-printing technique and is a useful addition to the current monitoring systems for surface water. By optimizing the flow cell, media composition, light harvesting and/or recA promotor sequence alterations the biosensor has the potential to detect lower concentrations of genotoxic compounds in surface water. Woutersen, M. (2013). Development And Validation Of An On-Line Water Toxicity Sensor Based On Genetically Modified, Luminescent Bacteria (Doctoral Dissertation)

ENWISS – Qualitative Evaluation ohne Folgen?

Spätestens im Gefolge des Bologna-Prozesses werden Qualitätssicherung und damit einhergehende Lehr- und Forschungsevaluationen ein Pflichtthema für Universitäten. Doch ungenaue Vorgaben über Form, Methode, Umfang und Veröffentlichung von Evaluationsvorhaben und deren Ergebnisse sowie die häufig unmittelbare&nbsp; Verknüpfung&nbsp; von&nbsp; Strukturevaluation&nbsp; mit&nbsp; wirtschaftlichen Gesichtspunkten, verschaffen Evaluationen ein schweres Standing bei den Statusgruppen der Hochschulen. Das Evaluationsnetzwerk Wissenschaft (ENWISS) der Technischen Universität Darmstadt verspricht durch seine Koordinationsform des Peer-Netzwerks eine alternative Arbeitsweise. Evaluation soll nicht als Instrument von ökonomisch motiviertem Qualitätsmanagement, sondern wissenschaftlich-empirisch legitimierter Qualitätsentwicklung verstanden werden. Wie wird die Evaluation nach ENWISS von den Betroffenen wahrgenommen? Lassen sich damit die Bedenken gegenüber dem Evaluationsboom ausräumen? Wie reagieren die Universitätsleitungen, die ja die Auftraggeber derartiger Evaluationsprozesse sind, auf die Ergebnisse von ENWISS? Bologna refoms at universities are accompanied by strategies of quality management, i.e. evaluation of teaching and research. Meanwhile, among the different status groups at the university evaluation is not really highly estimated. Reasons therefore are lack of information concerning shape, method, scale and publication of evaluation and its results as well as the coupling of evaluation results and eco- nomic planning. The Evaluation Network Science (ENWISS) of the Technical University Darmstadt promises an alternative way of quality management through peer networking. Evaluation here is not understood as an instrument of economically driven quality management but as a scientifically legitimated way of quality development. How do university members involved in ENWISS perceive this evaluation method? Can ENWISS overcome criticism on evaluation as such? How do university headships, the initiators of processes of evaluation, react on ENWISS results

Orexin-A measurement in narcolepsy : A stability study and a comparison of LC-MS/MS and immunoassays

Background: Orexin-A and-B are neuropeptides involved in sleep-wake regulation. In human narcolepsy type 1, this cycle is disrupted due to loss of orexin-producing neurons in the hypothalamus. Cerebrospinal fluid (CSF) orexin-A measurement is used in the diagnosis of narcolepsy type 1. Currently available immunoassays may lack specificity for accurate orexin quantification. We developed and validated a liquid chromatography mass spectrometry assay (LC-MS/MS) for CSF orexin-A and B. Methods: We used CSF samples from narcolepsy type 1 (n = 22) and type 2 (n = 6) and non-narcoleptic controls (n = 44). Stable isotope-labeled orexin-A and-B internal standards were added to samples before solid-phase extraction and quantification by LC-MS/MS. The samples were also assayed by commercial radioimmunoassay (RIA, n = 42) and enzymatic immunoassay (EIA, n = 72) kits. Stability of orexins in CSF was studied for 12 months. Results: Our assay has a good sensitivity (10 pmol/L = 35 pg/mL) and a wide linear range (35-3500 pg/mL). Added orexin-A and-B were stable in CSF for 12 and 3 months, respectively, when frozen. The median orexin-A concentration in CSF from narcolepsy type 1 patients was <35 pg/mL (range <35-131 pg/mL), which was lower than that in CSF from control individuals (98 pg/mL, range <35-424 pg/mL). Orexin-A concentrations determined using our LC-MS/MS assay were five times lower than those measured with a commercial RIA. Orexin-B concentrations were undetectable Conclusions: Orexin-A concentrations measured by our LC-MS/MS assay were lower in narcolepsy type 1 patients as compared to controls. RIA yielded on average higher concentrations than LC-MS/MS.Peer reviewe

Development of individual competencies and team performance in interprofessional ward rounds: results of a study with multimodal observations at the Heidelberg Interprofessional Training Ward.

INTRODUCTION Interprofessional training wards (IPTW) aim to improve undergraduates' interprofessional collaborative practice of care. Little is known about the effects of the different team tasks on IPTW as measured by external assessment. In Heidelberg, Germany, four nursing and four medical undergraduates (= one cohort) care for up to six patients undergoing general surgery during a four-week placement. They learn both professionally and interprofessionally, working largely on their own responsibility under the supervision of the medical and nursing learning facilitators. Interprofessional ward rounds are a central component of developing individual competencies and team performance. The aim of this study was to evaluate individual competencies and team performance shown in ward rounds. METHODS Observations took place in four cohorts of four nursing and four medical undergraduates each. Undergraduates in one cohort were divided into two teams, which rotated in morning and afternoon shifts. Team 1 was on morning shift during the first (t0) and third (t1) weeks of the IPTW placement, and Team 2 was on morning shift during the second (t0) and fourth (t1) weeks. Within each team, a tandem of one nursing and one medical undergraduate cared for a patient room with three patients. Ward round observations took place with each team and tandem at t0 and t1 using the IP-VITA instrument for individual competencies (16 items) and team performance (11 items). Four hypotheses were formulated for statistical testing with linear mixed models and correlations. RESULTS A total of 16 nursing and medical undergraduates each were included. There were significant changes in mean values between t0 and t1 in individual competencies (Hypothesis 1). They were statistically significant for all three sum scores: "Roles and Responsibilities", Patient-Centeredness", and "Leadership". In terms of team performance (Hypothesis 2), there was a statistically significant change in mean values in the sum score "Roles and Responsibilities" and positive trends in the sum scores "Patient-Centeredness" and "Decision-Making/Collaborative Clinical Reasoning". Analysis of differences in the development of individual competencies in the groups of nursing and medical undergraduates (Hypothesis 3) showed more significant differences in the mean values of the two groups in t0 than in t1. There were significant correlations between individual competencies and team performance at both t0 and t1 (Hypothesis 4). DISCUSSION The study has limitations due to the small sample and some sources of bias related to the external assessment by means of observation. Nevertheless, this study offers insights into interprofessional tasks on the IPTW from an external assessment. Results from quantitative and qualitative analysis of learners self-assessment are confirmed in terms of roles and responsibilities and patient-centeredness. It has been observed that medical undergraduates acquired and applied skills in collaborative clinic reasoning and decision-making, whereas nursing undergraduates acquired leadership skills. Within the study sample, only a small group of tandems remained constant over time. In team performance, the group of constant tandems tended to perform better than the group of random tandems. The aim of IPTW should be to prepare healthcare team members for the challenge of changing teams. Therefore, implications for IPTW implementation could be to develop learning support approaches that allow medical and nursing undergraduates to bring interprofessional competencies to team performance, independent of the tandem partner or team

Development and Validation of an On-Line Water Toxicity Sensor with Immobilized Luminescent Bacteria for On-Line Surface Water Monitoring.

Surface water used for drinking water production is frequently monitored in The Netherlands using whole organism biomonitors, with for exampleDaphnia magnaorDreissenamussels, which respond to changes in the water quality. However, not all human-relevant toxic compounds can be detected by these biomonitors. Therefore, a new on-line biosensor has been developed, containing immobilized genetically modified bacteria, which respond to genotoxicity in the water by emitting luminescence. The performance of this sensor was tested under laboratory conditions, as well as under field conditions at a monitoring station along the river Meuse in The Netherlands. The sensor was robust and easy to clean, with inert materials, temperature control and nutrient feed for the reporter organisms. The bacteria were immobilized in sol-gel on either an optical fiber or a glass slide and then continuously exposed to water. Since the glass slide was more sensitive and robust, only this setup was used in the field. The sensor responded to spikes of genotoxic compounds in the water with a minimal detectable concentration of 0.01 mg/L mitomycin C in the laboratory and 0.1 mg/L mitomycin C in the field. With further optimization, which should include a reduction in daily maintenance, the sensor has the potential to become a useful addition to the currently available biomonitors

Evaluation of Prognostic Parameters to Identify Aggressive Penile Carcinomas

Background: Advanced penile carcinoma is characterized by poor prognosis. Most data on prognostic factors are based on small study cohorts, and even meta-analyses are limited in patient numbers. Therefore, there is still a lack of evidence for clinical decisions. In addition, the most recent TNM classification is questionable; in line with previous studies, we found that it has not improved prognosis estimation. Methods: We evaluated 297 patients from Germany, Russia, and Portugal. Tissue samples from 233 patients were re-analyzed by two experienced pathologists. HPV status, p16, and histopathological parameters were evaluated for all patients. Results: Advanced lymph node metastases (N2, N3) were highly significantly associated with reductions in metastasis-free (MFS), cancer-specific (CS), and overall survival (OS) rates (p = <0.001), while lymphovascular invasion was a significant parameter for reduced CS and OS (p = 0.005; p = 0.007). Concerning the primary tumor stage, a significant difference in MFS was found only between pT1b and pT1a (p = 0.017), whereas CS and OS did not significantly differ between T categories. In patients without lymph node metastasis at the time of primary diagnosis, lymphovascular invasion was a significant prognostic parameter for lower MFS (p = 0.032). Histological subtypes differed in prognosis, with the worst outcome in basaloid carcinomas, but without statistical significance. HPV status was not associated with prognosis, either in the total cohort or in the usual type alone. Conclusion: Lymphatic involvement has the highest impact on prognosis in penile cancer, whereas HPV status alone is not suitable as a prognostic parameter. The pT1b stage, which includes grading, as well as lymphovascular and perineural invasion in the T stage, seems questionable; a revision of the TNM classification is therefore required