Two Optimal Strategies for Active Learning of Causal Models from Interventional Data

From observational data alone, a causal DAG is only identifiable up to Markov equivalence. Interventional data generally improves identifiability; however, the gain of an intervention strongly depends on the intervention target, that is, the intervened variables. We present active learning (that is, optimal experimental design) strategies calculating optimal interventions for two different learning goals. The first one is a greedy approach using single-vertex interventions that maximizes the number of edges that can be oriented after each intervention. The second one yields in polynomial time a minimum set of targets of arbitrary size that guarantees full identifiability. This second approach proves a conjecture of Eberhardt (2008) indicating the number of unbounded intervention targets which is sufficient and in the worst case necessary for full identifiability. In a simulation study, we compare our two active learning approaches to random interventions and an existing approach, and analyze the influence of estimation errors on the overall performance of active learning

Automatisierte Klassifikation nach WRB 2015 mit KA 5-konformen Daten – Qualität der Ableitung bei beschränkten Daten

Zur Verwendung in großen Profildatenbanken wurde eine Datenbankanwendung erstellt, die Bodennamen nach World Reference Base for Soil Resources 2014, update 2015 (WRB) automatisiert aus Profilbeschrieben nach Bodenkundlicher Kartieranleitung und Labordaten ableitet. Mit einem Datensatz von 201 gut beschriebenen Profilen aus Deutschland, Österreich und der Schweiz wurden die Auswirkungen von fehlenden Daten auf die Qualität der Ableitung geprüft. Insbesondere sind Ableitungen allein aus dem Horizontsymbol ebenso wenig erfolgversprechend wie Ableitungen ohne Horizontsymbolinformation. Wir schließen daraus, dass Bodenmerkmale ohne eine grundsätzliche Einordnung in einen genetischen Zusammenhang nicht im Nachhinein genetisch interpretierbar sind. Da die Auswertungen sehr komplex sind, kann dies auch für andere Datenauswertungen als gültig angenommen werden

Treatment decisions, clinical outcomes, and pharmacoeconomics in the treatment of patients with EGFR mutated stage III/IV NSCLC in Germany: an observational study

Background: We evaluated treatment decisions and outcomes in a cohort of predominately Caucasian patients with EGFR mutation-positive (EGFR Mut+) non-small-cell lung cancer (NSCLC). Methods: REASON (NCT00997230) was a non-interventional study in German patients with stage IIIB/IV NSCLC. Secondary endpoints for EGFR Mut + NSCLC included progression-free survival (PFS), overall survival (OS), adverse event (AE) management, and pharmacoeconomic outcomes. Results: Among 334 patients with EGFR Mut + NSCLC, tyrosine kinase inhibitors (TKIs) were the most common first-line therapy (56.6%, 53.0% gefitinib). Among patients who received TKIs/gefitinib before first disease progression, PFS was longer compared with those who did not receive a TKI (median 10.1/10.0 vs. 7.0 months; HR 0.67/0.69; log-rank p = 0.012/p = 0.022). OS was longer for those patients who ever received a TKI/gefitinib during their complete therapy course compared with those who never received a TKI (median 18.4/18.1 vs. 13.6 months; HR 0.53/0.55; p = 0.003/p = 0.005). Total mean first-line treatment healthcare costs per person were higher for those receiving TKIs (€46,443) compared with those who received chemotherapy (€27,182). Mean outpatient and inpatient costs were highest with chemotherapy. Rash, diarrhea, and dry skin were the most commonly reported AEs for patients receiving gefitinib. Conclusions: In REASON, TKI therapy was the most common first- and second-line treatment for EGFR Mut + NSCLC, associated with increased drug costs compared with chemotherapy. Patients who received gefitinib or a TKI ever during their complete therapy course had prolonged PFS and OS compared with patients who did not receive a TKI. Trial registration: The trial was registered on October, 2009 with ClinicalTrials.gov : https://clinicaltrials.gov/ct2/show/NCT00997230?term=NCT00997230&rank=

Successful treatment of a recurrent granulation polyp in the airways with high-dose-rate brachytherapy: a case report

Background Benign central airway tumors are very rare diseases. Their unspecific symptoms are responsible for late diagnosis. Endoscopic interventions with different techniques and tools are widely used for their treatment. However, in certain cases interventional endoscopy might be unsuccessful and therefore other methods such as high-dose-rate brachytherapy could be a therapeutic option. Case presentation A 76-year-old white German woman was referred to our clinic for an endoscopic treatment of a recurrent granulation polyp in her left main bronchus. She had dyspnea, coughing, and mucus retention. Three times resections via bronchoscopy were performed within less than a year. After each intervention the polyp regrew inside her left main bronchus causing a repeat of the initial symptoms. She presented to our clinic less than 1 month since the last intervention. Twice we performed a rigid bronchoscopy in total anesthesia where we resected the granulation polyp with a snare wire loop and did an argon plasma coagulation of its base. Due to the recurrent growing of the granuloma, we performed a high-dose-rate brachytherapy in conscious sedation after another interventional bronchoscopy with a resection of the polyp and argon plasma coagulation of the base. Three months after brachytherapy our patient came to our clinic for a follow-up with none of the initial symptoms. Only a small remnant of the polyp without a significant occlusion of her bronchus was visualized by bronchoscopy. Furthermore, 6 months after brachytherapy she was not presenting any of the initial symptoms. Conclusions This case report shows that high-dose-rate brachytherapy is a therapeutic option for the treatment of benign airway stenosis when other interventional treatments are not or are less than successful. However, further investigations are needed to prove the effectiveness and reliability of the method

Multivariate Parametric Density Estimation Based On The Modified Cramér-von Mises Distance

In this paper, a novel distance-based density estimation method is proposed, which considers the overall density function in the goodness-of-fit. In detail, the parameters of Gaussian mixture densities are estimated from samples, based on the distance of the cumulative distributions over the entire state space. Due to the ambiguous definition of the standard multivariate cumulative distribution, the Localized Cumulative Distribution and a modified Cram\\u27{e}r-von Mises distance measure are employed. A further contribution is the derivation of a simple-to-implement optimization procedure for the optimization problem. The proposed approach\u27s good performance in estimating arbitrary Gaussian mixture densities is shown in an experimental comparison to the Expectation Maximization algorithm for Gaussian mixture densities

Bodenklassifizierung nach WRB mit Bodendaten nach Kartieranleitung

Die internationale Bodenklassifikation World Reference Base for Soil Resources (WRB) wird in der internationalen fachlichen wie administrativen Arbeit zur Benennung von Böden verwendet. Die Klassifizierung erfolgt nicht wie in der deutschen Bodensystematik aufgrund der Folge der im Profil vorkommenden morphogenetischen Horizonte, sondern durch Betrachtung des Gesamtprofils hinsichtlich unterschiedlicher Eigenschaften. Dies führt zu Problemen mit in Datenbanken abgelegten Bodendaten, die allgemein neben den Profilmerkmalen morphogenetische Horizonte beschreiben. Einige dieser Probleme werden beispielhaft vorgestellt, darunter die Festlegung der Grenzen diagnostischer Horizonte, sei es wegen der Art der Beschreibung der Horizontgrenzen, unscharfer Definitionen in der WRB oder wegen der Datenstrukturen der Bodendatenbanken, und die Problematik des abrupten Bodenartenwechsels. Es wird ein algorithmen-basierter Ansatz vorgestellt, mit dem die diagnostischen Horizonte, Materialien und Eigenschaften der WRB sowie die für die Benennung benötigten Namensbestandteile Referenzbodengruppe, Qualifier und Specifier aus den Profilbeschrieb-Daten nach KA5 und Labordaten ermittelt werden können. Die Algorithmen sind so angelegt, dass die Einzelparameter in absteigender Reihenfolge der Zuverlässigkeit für die Ableitung abgefragt werden. Mithilfe von im Gelände nach KA5 beschriebenen und nach WRB klassifizierten Fahlerdeprofilen aus Brandenburg wird die Zuverlässigkeit der Ableitungen geprüft. In einem Ausblick sollen mögliche Konsequenzen der Arbeiten für eine Verbesserung der Klassifikation ebenso diskutiert werden wie Vorschläge zur Verbesserung der Datenaufnahme, um eine Klassifizierung nach WRB zu vereinfachen

Ableitungsschlüssel WRB 2007 aus Bodendaten nach KA 5

Bodennamen nach World Reference Base for Soil Resources (WRB) werden automa-tisiert aus Profilbeschrieben nach Boden-kundlicher Kartieranleitung (Ad-hoc AG BODEN 2005, weiter als KA 5) und Labor-daten abgeleitet. Die Datenbankanwen-dung wurde mit einen umfangreichen Pro-fildatensatz aus dem Fachinformations-system Bodengeologie des Landesamtes für Bergbau, Geologie und Rohstoffe Bran-denburg getestet. Über 90 Prozent richtig erkannte Diagnostika und Namenselemen-te der WRB zeigen das Potential des im-plementierten Verfahrens. Die MS Access-Anwendung ist frei zugänglich unter: www.bgr.bund.de/uebersetzungsschluessel

Comparing Factors Influencing Heavy Episodic Drinking of Young Adults in the United Kingdom and The Netherlands

The United Kingdom and the Netherlands exhibit similar levels of heavy episodic drinking but different drinking patterns among youths. This study aimed to assess the impact of country of residence on heavy episodic drinking among 293 British and Dutch youths, accounting for other behavioral determinants. Participants completed online questionnaires measuring impulsivity, sensation-seeking, alcohol consumption, and constructs from the Theory of Planned Behavior [TPB]. Mediation analysis established that British youths engaged in more frequent heavy drinking episodes than Dutch youths, as they had weaker intentions to refrain from heavy drinking, and lower perceived behavioral control. Country of residence also was a direct predictor of frequency of heavy drinking episodes, not mediated by personality traits. Thus, country of residence seems an important factor in heavy episodic drinking, partly mediated through TPB constructs. Interventions may benefit from targeting country-specific drinking behavior and related socio-psychological mechanisms.</p

ADAM10 is expressed in human podocytes and found in urinary vesicles of patients with glomerular kidney diseases

<p>Abstract</p> <p>Background</p> <p>The importance of the Notch signaling in the development of glomerular diseases has been recently described. Therefore we analyzed in podocytes the expression and activity of ADAM10, one important component of the Notch signaling complex.</p> <p>Methods</p> <p>By Western blot, immunofluorescence and immunohistochemistry analysis we characterized the expression of ADAM10 in human podocytes, human urine and human renal tissue.</p> <p>Results</p> <p>We present evidence, that differentiated human podocytes possessed increased amounts of mature ADAM10 and released elevated levels of L1 adhesion molecule, one well known substrate of ADAM10. By using specific siRNA and metalloproteinase inhibitors we demonstrate that ADAM10 is involved in the cleavage of L1 in human podocytes. Injury of podocytes enhanced the ADAM10 mediated cleavage of L1. In addition, we detected ADAM10 in urinary podocytes from patients with kidney diseases and in tissue sections of normal human kidney. Finally, we found elevated levels of ADAM10 in urinary vesicles of patients with glomerular kidney diseases.</p> <p>Conclusions</p> <p>The activity of ADAM10 in human podocytes may play an important role in the development of glomerular kidney diseases.</p