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[Background & Aims]: The existence of different subtypes of pancreatic ductal adenocarcinoma (PDAC) and their correlation with patient outcome have shifted the emphasis on patient classification for better decision-making algorithms and personalized therapy. The contribution of mechanisms regulating the cancer stem cell (CSC) population in different subtypes remains unknown. [Methods]: Using RNA-seq, we identified B-cell CLL/lymphoma 3 (BCL3), an atypical nf-κb signaling member, as differing in pancreatic CSCs. To determine the biological consequences of BCL3 silencing in vivo and in vitro, we generated bcl3-deficient preclinical mouse models as well as murine cell lines and correlated our findings with human cell lines, PDX models, and 2 independent patient cohorts. We assessed the correlation of bcl3 expression pattern with clinical parameters and subtypes. [Results]: Bcl3 was significantly down-regulated in human CSCs. Recapitulating this phenotype in preclinical mouse models of PDAC via BCL3 genetic knockout enhanced tumor burden, metastasis, epithelial to mesenchymal transition, and reduced overall survival. Fluorescence-activated cell sorting analyses, together with oxygen consumption, sphere formation, and tumorigenicity assays, all indicated that BCL3 loss resulted in CSC compartment expansion promoting cellular dedifferentiation. Overexpression of BCL3 in human PDXs diminished tumor growth by significantly reducing the CSC population and promoting differentiation. Human PDACs with low BCL3 expression correlated with increased metastasis, and BCL3-negative tumors correlated with lower survival and nonclassical subtypes. [Conclusions]: We demonstrate that bcl3 impacts pancreatic carcinogenesis by restraining CSC expansion and by curtailing an aggressive and metastatic tumor burden in PDAC across species. Levels of BCL3 expression are a useful stratification marker for predicting subtype characterization in PDAC, thereby allowing for personalized therapeutic approaches., This work was supported by the Deutsche Forschungsgemeinschaft (grants AL 1174/4-1, AL1174/4-2, and Collaborative Research Center 1321 “Modeling and Targeting Pancreatic Cancer” to Hana Algül; SFB824 Z2 to Katja Steiger), the Deutsche Krebshilfe (grant 111646 to Hana Algül), a Ramon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain (to Bruno Sainz Jr), a Coordinated Grant from Fundación Asociación Española Contra el Cáncer (GC16173694BARB to Bruno Sainz Jr), funding from The Fero Foundation (to Bruno Sainz Jr), and a Proyecto de Investigacion de Salud, ISCIII, Spain (no. PI18/00757 to Bruno Sainz Jr). Jiaoyu Ai is supported by the “China Scholarship Council” grant program.

An open-source sea ice drift algorithm for Sentinel-1 SAR imagery is introduced based on the combination of feature tracking and pattern matching. Feature tracking produces an initial drift estimate and limits the search area for the consecutive pattern matching, which provides small- to medium-scale drift adjustments and normalised cross-correlation values. The algorithm is designed to combine the two approaches in order to benefit from the respective advantages. The considered feature-tracking method allows for an efficient computation of the drift field and the resulting vectors show a high degree of independence in terms of position, length, direction and rotation. The considered pattern-matching method, on the other hand, allows better control over vector positioning and resolution. The preprocessing of the Sentinel-1 data has been adjusted to retrieve a feature distribution that depends less on SAR backscatter peak values. Applying the algorithm with the recommended parameter setting, sea ice drift retrieval with a vector spacing of 4 km on Sentinel-1 images covering 400 km × 400 km, takes about 4 min on a standard 2.7 GHz processor with 8 GB memory. The corresponding recommended patch size for the pattern-matching step that defines the final resolution of each drift vector is 34 × 34 pixels (2.7 × 2.7 km). To assess the potential performance after finding suitable search restrictions, calculated drift results from 246 Sentinel-1 image pairs have been compared to buoy GPS data, collected in 2015 between 15 January and 22 April and covering an area from 80.5 to 83.5° N and 12 to 27° E. We found a logarithmic normal distribution of the displacement difference with a median at 352.9 m using HV polarisation and 535.7 m using HH polarisation. All software requirements necessary for applying the presented sea ice drift algorithm are open-source to ensure free implementation and easy distribution.

Rationale: Pancreatic ductal adenocarcinoma (PDAC) remains a tumor entity of exceptionally poor prognosis, and several biomarkers are under current investigation for the prediction of patient prognosis. Many studies focus on promoting newly developed imaging biomarkers without a rigorous comparison to other established parameters. To assess the true value and leverage the potential of all efforts in this field, a multi-parametric evaluation of the available biomarkers for PDAC survival prediction is warranted. Here we present a multiparametric analysis to assess the predictive value of established parameters and the added contribution of newly developed imaging features such as biomarkers for overall PDAC patient survival. Methods: 103 patients with resectable PDAC were retrospectively enrolled. Clinical and histopathological data (age, sex, chemotherapy regimens, tumor size, lymph node status, grading and resection status), morpho-molecular and genetic data (tumor morphology, molecular subtype, tp53, kras, smad4 and p16 genetics), image-derived features and the combination of all parameters were tested for their prognostic strength based on the concordance index (CI) of multivariate Cox proportional hazards survival modelling after unsupervised machine learning preprocessing. Results: The average CIs of the out-of-sample data were: 0.63 for the clinical and histopathological features, 0.53 for the morpho-molecular and genetic features, 0.65 for the imaging features and 0.65 for the combined model including all parameters. Conclusions: Imaging-derived features represent an independent survival predictor in PDAC and enable the multiparametric, machine learning-assisted modelling of postoperative overall survival with a high performance compared to clinical and morpho-molecular/genetic parameters. We propose that future studies systematically include imaging-derived features to benchmark their additive value when evaluating biomarker-based model performance.

A novel generic sensor model is introduced for testing and validation of ADAS/AD (Advanced Driver Assistance Systems/Autonomous Drive) functions. The model converts an incoming object list into a sensor specific object list and is suitable for all ADAS/AD perception sensors operating on object level. The field of view of the sensor is represented by a two dimensional polygon, that can be defined by a set of points. A simple ray-tracing method is applied to simulate coverage by objects. The model allows multiple range specifications for a single sensor depending on object type and classification capabilities. A look-up table is used to convert the object class definitions of the virtual environment into the class definitions of the considered sensor. Additional object parameters that are detected by the sensor may be included. False negative and false positive detections are generated by probabilistic functions. The parametrisation procedure of the sensor model is explained and depicted in an example using the data sheet of the Radar Continental ARS404. The model's capability to simulate a complete sensor set is demonstrated with the sensor set of the Renault Zoe that was used to collect the nuScenes data set. The sensor model is integrated into a virtual test-bed using Vires VTD and Open Simulation Interface.

Purpose The use of organs from polytrauma donors is reported to be associated with impaired results. Thus, radiological signs of lung contusions are a clear reason for many centers to reject an organ offer. This results in the loss of potentially viable organs for the donor pool. Methods We analysed a total of 751 patients who received standard double lung transplantation between January 2010 and June 2018 in our institution. A total of 102 patients were transplanted using lungs from polytrauma donors. These cases were divided into two groups: Group I (n=46) - polytrauma donors who had radiological signs of lung contusion; Group II (n=56) - polytrauma donors with a normal chest radiography. A total of 649 transplantations with non-trauma donors were assigned to Group III. Short- and long-term outcomes of the three groups were compared. Results Basic demographic data and preoperative factors of the recipients of the three groups were comparable. Donors in Group I and II were significantly younger with a median of 22 and 36 years, respectively, while median age in Group III was 44 years (p Conclusion Lung transplantation using organs from polytrauma donors leads to comparable short- and long-term results compared to non-trauma donors. The presence or absence of radiological signs of lung contusion did not impact primary graft function and survival.

Background The prognostic impact of liver steatosis in obese patients is well established. Limited data on the risk factors for and impact of hepatic steatosis in lean patients are available. Aims Assess risk factors for liver steatosis in lean patients and investigate its impact on survival. Methods Patients without viral hepatitis and with a BMI ≤ 25 kg/m2 undergoing liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by transient elastography were retrospectively identified. Clinical characteristics and laboratory test results were obtained at the time of LSM/CAP measurement. National death registry data were obtained in order to assess survival. Results Among n = 218 lean patients, n = 97 (34.5%) showed significant liver steatosis (CAP ≥ 268 dB/m), while n = 184 (65.5%) had no or just mild steatosis (CAP

Statins reduce cardiovascular risk. However, “real-life” data on statin use in patients with chronic liver disease and its impact on overall and liver-related survival are limited. Therefore, we assessed 1265 CLD patients stratified as advanced (ACLD) or non-advanced (non-ACLD) stage. Statin indication was evaluated according to the 2013 ACC/AHA guidelines and survival-status was verified by national death registry data. Overall, 122 (9.6%) patients had an indication for statin therapy but did not receive statins, 178 (14.1%) patients were on statins and 965 (76.3%) patients had no indication for statins. Statin underutilization was 34.2% in non-ACLD and 48.2% in ACLD patients. In non-ACLD patients, survival was worse without a statin despite indication as compared to patients on statin or without indication (log-rank p = 0.018). In ACLD patients, statin use did not significantly impact on survival (log-rank p = 0.264). Multivariate cox regression analysis confirmed improved overall survival in patients with statin as compared to patients with indication but no statin (HR 0.225; 95%CI 0.053–0.959; p = 0.044) and a trend towards reduced liver-related mortality (HR 0.088; 95%CI 0.006–1.200; p = 0.068). This was not observed in ACLD patients. In conclusion, guideline-confirm statin use is often withhold from patients with liver disease and this underutilization is associated with impaired survival in non-ACLD patients.

Purpose Development of a supervised machine-learning model capable of predicting clinically relevant molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) from diffusion-weighted-imaging-derived radiomic features. Methods The retrospective observational study assessed 55 surgical PDAC patients. Molecular subtypes were defined by immunohistochemical staining of KRT81. Tumors were manually segmented and 1606 radiomic features were extracted with PyRadiomics. A gradient-boosted-tree algorithm was trained on 70% of the patients (N = 28) and tested on 30% (N = 17) to predict KRT81+ vs. KRT81- tumor subtypes. A gradient-boosted survival regression model was fit to the disease-free and overall survival data. Chemotherapy response and survival were assessed stratified by subtype and radiomic signature. Radiomic feature importance was ranked. Results The mean±STDEV sensitivity, specificity and ROC-AUC were 0.90±0.07, 0.92±0.11, and 0.93±0.07, respectively. The mean±STDEV concordance indices between the disease-free and overall survival predicted by the model based on the radiomic parameters and actual patient survival were 0.76±0.05 and 0.71±0.06, respectively. Patients with a KRT81+ subtype experienced significantly diminished median overall survival compared to KRT81- patients (7.0 vs. 22.6 months, HR 4.03, log-rank-test P =

The Economy for the Common Good (ECG) pursues an alternative economic model built on values oriented to the common welfare such as human dignity, solidarity, ecological sustainability, social justice, transparency and democratic participation. The principles endorsed by the ECG coincide with those of the social economy as it promotes a system in which the motivation of economic competition is replaced by cooperation so that the collective interest and common good is put above companies’ profits. (High) quality of work plays an important role in the ECG. The main points of its work-related values can be summarised by the willingness to elude discrimination and employment precariousness; the encouragement of information and worker participation; and the promotion of beneficial psychosocial factors at work. However, there is scarce knowledge on the actual labour conditions of workers employed in such type of firms. Thus, in this paper, our goal is to describe the quality of jobs in companies following the Economy for the Common Good in Austria and Germany, the countries where this economic model is most widespread. Using data published in the Common Good Balances reports available on the ECG website1 , we extracted data informing about job quality at an organisational level of 59 firms with at least 5 employees in Austria and Germany. Although the breadth and depth of the information collected in the Common Good Balances reports is variable, results suggest a widespread presence of elements of good quality of work: limited use of precarious employment arrangements (yet, thorough information about fixedterm contracts is lacking), provision of training and a decent degree of decisionmaking autonomy. Direct participation practices are more prevailing than representative participation forms.

In diesem Kapitel beschaftigen wir uns mit der Gesundheit, der Lebenszufriedenheit und dem Sozialkapital von Migrant_innen und Osterreicher_innen. Fur dieses Thema werden wir zunachst den Begriff der Gesundheit naher erlautern sowie das Anforderungs-Ressourcen-Modell zur Erklarung von Gesundheit betrachten (Renneberg und Hammelstein 2006). Anschliesend befassen wir uns naher mit dem Sozialkapital sowie dessen theoretischem und empirischem Einfluss auf die Gesundheit.

Osterreich weist seit jeher eine bewegte Einwanderungsgeschichte auf. Schon in der zweiten Halfte des 19. Jahrhunderts fand eine Massenzuwanderung nach Wien sowie in die Industrieregionen im Osten statt. In der Folge stieg die Einwohnerzahl Wiens von einer halben auf zwei Millionen.

Cancer precision medicine has opened up new avenues for the treatment of colorectal cancer (CRC). To fully realize its potential, high-throughput sequencing platforms that allow genotyping beyond KRAS need to be implemented and require performance assessment. We comprehensively analyzed first-year data of 202 consecutive formalin-fixed paraffin embedded (FFPE) CRC samples for which prospective genotyping at our institution was requested. Deep targeted genotyping was done using a semiconductor-based sequencing platform and a self-designed panel of 30 CRC-related genes. Additionally, microsatellite status (MS) was determined. Ninety-seven percent of tumor samples were suitable for sequencing and in 88% MS could be assessed. The minimal drop-out rates of 6 and 25 cases, respectively were due to too low amounts or heavy degradation of DNA. Of 557 nonsynonymous mutations, 90 (16%) have not been described in COSMIC at the time of data query. Forty-three cases (22%) had double- or triple mutations affecting a single gene. Sixty-four percent had genetic alterations influencing oncological therapy. Eight percent of patients (MSI phenotype: 6%; mutated POLE: 2%) were potentially eligible for treatment with immune checkpoint inhibitors. Of 56% of KRASwt CRC that potentially qualified for anti-EGFR treatment, 30% presented with mutations in BRAF/NRAS. Mutated PIK3CA was detected in 21%. In conclusion, we here present real-life routine diagnostics data that not only demonstrate the robustness and feasibility of deep targeted sequencing and MS-analysis of FFPE CRC samples but also contribute to the understanding of CRC genetics. Most importantly, in more than half of the patients our approach enabled the selection of the best treatment currently available. © 2016 Wiley Periodicals, Inc.

Development and validation of reliable environment perception systems for automated driving functions requires the extension of conventional physical test drives with simulations in virtual test environments. In such a virtual test environment, a perception sensor is replaced by a sensor model. A major challenge for state-of-the-art sensor models is to represent the large variety of material properties of the surrounding objects in a realistic manner. Since lidar sensors are considered to play an essential role for upcoming automated vehicles, this paper presents a new lidar modelling approach that takes material properties and corresponding lidar capabilities into account. The considered material property is the incidence angle dependent reflectance of the illuminated material in the infrared spectrum and the considered lidar property its capability to detect a material with a certain reflectance up to a certain range. A new material classification for lidar modelling in the automotive context is suggested, distinguishing between 7 material classes and 23 subclasses. To measure angle dependent reflectance in the infrared spectrum, a new measurement device based on a time of flight camera is introduced and calibrated using Lambertian targets with defined reflectance values at 10 % , 50 % , and 95 % . Reflectance measurements of 9 material subclasses are presented and 488 spectra from the NASA ECOSTRESS library are considered to evaluate the new measurement device. The parametrisation of the lidar capabilities is illustrated by presenting a lidar measurement campaign with a new Infineon lidar prototype and relevant data from 12 common lidar types.

Synthetic Aperture Radar (SAR) data from RADARSAT-2 (RS2) in dual-polarization mode provide additional information for discriminating sea ice and open water compared to single-polarization data. We have developed an automatic algorithm based on dual-polarized RS2 SAR images to distinguish open water (rough and calm) and sea ice. Several technical issues inherent in RS2 data were solved in the pre-processing stage, including thermal noise reduction in HV polarization and correction of angular backscatter dependency in HH polarization. Texture features were explored and used in addition to supervised image classification based on the support vector machines (SVM) approach. The study was conducted in the ice-covered area between Greenland and Franz Josef Land. The algorithm has been trained using 24 RS2 scenes acquired in winter months in 2011 and 2012, and the results were validated against manually derived ice charts of the Norwegian Meteorological Institute. The algorithm was applied on a total of 2705 RS2 scenes obtained from 2013 to 2015, and the validation results showed that the average classification accuracy was 91 ± 4 %.

A satellite database including 16 555 satellite images and ice charts displaying the area of Isfjorden, Hornsund, and the Svalbard region has been established with focus on the time period 2000–2014. 3319 manual interpretations of sea ice conditions have been conducted, resulting in two time series dividing the area of Isfjorden and Hornsund into "fast ice" (sea ice attached to the coastline), "drift ice", and "open water". The maximum fast ice coverage of Isfjorden is > 40 % in the periods 2000–2005 and 2009–2011 and stays 40 % in all considered years, except for 2012 and 2014, where the maximum stays

Die Weltgesundheitsorganisation (WHO) macht in der Ottawa Charta von 1986 auf die wichtige Rolle der Arbeit bzw. der Arbeitsbedingungen im Kontext des Gesundheitszustands der Bevolkerung aufmerksam: „Die sich verandernden Lebens-, Arbeits- und Freizeitbedingungen haben entscheidenden Einfluss auf die Gesundheit. Die Art und Weise, wie eine Gesellschaft die Arbeit, die Arbeitsbedingungen und die Freizeit organisiert, sollte eine Quelle der Gesundheit und nicht der Krankheit sein“ (WHO 1986, S. 3). In diesem Zusammenhang ruckte in der medizin- bzw. gesundheitssoziologischen Forschung das Konzept sozialer Determinanten der Gesundheit in den Mittelpunkt der Diskussion.

Im Rahmen des bio-psychosozialen Paradigmas wird angenommen, dass Anforderungen und Ressourcen die Gesundheit der Individuen beeinflussen (Freidl 1997). Diese Anforderungen und Ressourcen finden sich auf der Makroebene, der Mesoebene und der Mikroebene. Auf der Makroebene haben unter anderem Rahmenbedingungen, wie zum Beispiel die Art und Ausgestaltung des Sozialversicherungssystems einen Einfluss auf die Gesundheit.

The B7/CD28/CTLA4 signaling cascade is the most thoroughly studied costimulatory pathway and blockade with CTLA4Ig (abatacept) or its derivative belatacept has emerged as a valuable option for pharmacologic immune modulation. Several clinical studies have ultimately led to the approval of belatacept for immunosuppression in kidney transplant recipients. Areas covered: This review will discuss the immunological background of costimulation blockade and recent preclinical data and clinical results of CTLA4Ig/belatacept. Expert commentary: The development of belatacept is a major advance in clinical transplantation. However, in spite of promising results in preclinical and clinical trials, clinical use remains limited at present, in part due to increased rates of acute rejection. Recent efforts showing encouraging progress in refining such protocols might be a step toward harnessing the full potential of costimulation blockade-based immunosuppression.

Question addressed by the studyThe value of induction therapy in lung transplantation is controversial. According to the ISHLT, only about 50% of patients transplanted within the last 10 years received induction therapy. We reviewed our institutional experience to investigate the impact of induction therapy on short- and long-term outcomes.Materials/patients and methodsBetween 2007 and 2015, 446 patients with a complete follow-up were included in this retrospective analysis. Analysis comprised long-term kidney function, infectious complications, incidence of rejection and overall survival.ResultsA total of 231 patients received alemtuzumab, 50 patients antithymocyte globulin (ATG) and 165 patients did not receive induction therapy (NI). The alemtuzumab group revealed the lowest rate of chronic kidney insufficiency (NI: 52.2%; ATG: 60%; alemtuzumab: 36.6%; p = 0.001). Both, the NI group (pConclusionAlemtuzumab induction therapy followed by reduced maintenance immunosuppression is associated with a better kidney function compared to no induction and ATG. Survival rate as well as freedom from ACR and CLAD were comparable between alemtuzumab and ATG.