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Seit einigen Jahren ist eine stetige Zunahme des Einsatzes von mechanischen extrakorporalen Herz-Kreislauf- und Lungenunterstutzungssystemen (ECLS/ECMO) zu verzeichnen. So wurden seit 2015 in Deutschland jahrlich bei etwa 3000 Patienten ECLS/ECMO-Systeme implantiert. Trotz dieser haufigen Anwendung der passageren Unterstutzungssysteme existieren zurzeit national und international nur Leitlinien zum Einsatz der ECMO/ECLS, die erkrankungsbezogene Teilaspekte komplexer Therapiekaskaden adressieren. Vor diesem Hintergrund erschien es notwendig, evidenzbasierte Empfehlungen zur ECLS/ECMO-Therapie im Hinblick auf Indikationen und das komplexe Patientenmanagement zu verfassen, in denen personelle, prozessuale und infrastrukturelle Anforderungen definiert werden. Aus diesem Grund erfolgte im Juli 2015 durch die Deutsche Gesellschaft fur Thorax‑, Herz- und Gefaschirurgie (DGTHG) die Anmeldung einer diesbezuglichen S3-Leitlinie bei der zustandigen Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF). Im Mittelpunkt der Leitlinie steht die klinische Anwendung der ECLS/ECMO-Therapie; erganzend werden auch strukturelle und okonomische Aspekte adressiert. Unter Federfuhrung der DGTHG wurde mit Einbindung von Experten aus Deutschland, Osterreich und der Schweiz, delegiert aus 11 AWMF-Fachgesellschaften, 5 weiteren Fachgesellschaften sowie der Patientenvertretung, die S3-Leitlinie im Februar 2021 publiziert. Dieser Artikel stellt eine kurze Zusammenfassung des methodischen Konzepts sowie aller konsentierten Empfehlungen fur jede bearbeitete Fragestellung der Leitlinie dar.

BACKGROUND: Postsurgical pleural infection is a life-threatening complication after implantation of artificial devices such as ventricular assist devices (VADs). The treatment can be challenging and the evidence in the literature is very limited. Here we report our multidisciplinary approach of the management of pleural infection after VAD implantation. METHODS: Between March 2014 and December 2019, 33 patients developed postoperative pleural infection after VAD implantation and underwent thoracic surgical intervention at our institution. All patients were prospectively enrolled in this analysis. Data were retrospectively analyzed. Primary outcome was the 90-day mortality rate. Length of ICU stay related to pleural infection, chest tube duration, re-thoracotomy rate and length of ventilatory support represented secondary outcomes. RESULTS: The 90-day mortality rate was 6% (2 patients). The mean ICU stay related to the pleural infection was 6 days (2–24 days). Video-assisted thoracoscopic surgery (VATS) was performed in all patients. Conversion to thoracotomy was necessary in 12 cases. Decortication and parietal pleurectomy in addition to hematoma and empyema removal was performed in all patients. Due to diffuse bleeding, packing of the thoracic cavity with temporary thoracic closure was necessary in 10 patients. Depacking was performed after a mean of 3 days (3–7 days). Recurrent empyema or bleeding after definitive chest closure was not observed. Lung resection was performed in 3 patients. CONCLUSIONS: Thoracic surgical management of pleural infection in patients after VAD implantation is challenging and complicated due to the inevitable anticoagulative therapy. A perioperative multidisciplinary management which includes the early involvement of thoracic surgical expertise helps to improve survival in this very complex patient cohort.

Dealing with highly configurable systems is generally very complex. Researchers and practitioners have conceived hundreds of different analysis techniques to deal with different aspects of configurable systems. One large focal point is the testing of configurable software. This is challenging due to the large number of possible configurations. Moreover, tests themselves are rarely configurable and instead built for specific configurations. However, existing tests need to be adapted to run on a different configuration. In this paper, we report on an experiment about automatically reusing existing tests in configurable systems. We used manually developed tests for specific configurations of three configurable systems and investigated how changing the configuration affects the tests. Subsequently, we employed an approach for automated reuse to generate new test variants (by reusing from existing ones) for combinations of previous configurations and compared their results to the ones from existing tests. Our results showed that we could directly reuse some tests for different configurations. Nonetheless, our automatically generated test variants generally yielded better results. Our generated tests had a higher or equal success rate to the existing tests in most cases. Even in the cases the success rate was equal, our generated tests generally had higher code coverage.

Mineralocorticoid receptor antagonists have beneficial effects on left ventricular remodeling, cardiac fibrosis, and arrhythmia in heart failure, but efficacy and safety in dialysis patients is less clear. We evaluated the effect of spironolactone on left ventricular mass (LVM), an independent predictor of all-cause and cardiovascular mortality, in hemodialysis patients. In this placebo-controlled, parallel-group trial, 97 hemodialysis patients (23% female; mean age 60.3 years) were randomized to spironolactone 50 mg once daily (n=50) or placebo (n=47). The primary efficacy endpoint was change in LVM index (LVMi) from baseline to 40 weeks as determined by cardiac magnetic resonance imaging. Safety endpoints were development of hyperkalemia and change in residual renal function. There was no significant change in LVMi in participants randomized to spironolactone compared to placebo (-2.86±11.87 vs. 0.41±10.84 g/m2). There was also no difference in the secondary outcomes of mean 24-hour systolic or diastolic ambulatory blood pressure, left ventricular ejection fraction, 6-minute walk test distance, or New York Heart Association functional class. Moderate hyperkalemia (pre-dialysis potassium levels of 6.0-6.5 mmol/L) was more frequent with spironolactone treatment (155 vs. 80 events), but severe hyperkalemia (≥6.5 mmol/L) was not (14 vs. 24 events). Changes in residual urine volume and measured glomerular filtration rate did not differ between groups. There were no deaths in the spironolactone group and 4 deaths in the placebo group. Thus, treatment with 50 mg spironolactone did not change left ventricular mass index, cardiac function, or blood pressure in hemodialysis patients. Spironolactone increased the frequency of moderate hyperkalemia, but did not increase severe hyperkalemia.

Developing interactive systems and testing with realistic scenarios requires a detailed understanding of how these systems are used in their real environment. In this paper, we report on our experience from implementing a usage monitoring approach for the touch-enabled human machine interface of an industrial machine. The approach supports automated recording of user interface events as basis for analyzing interactions of users with the system. It collects information about navigation paths to different screens, activities on these screens, and the usage of functionality provided by the application. We evaluated three different approaches to integrate the required usage monitoring into the UI, considering aspects such as necessary changes to the existing code base, dependencies to third-party libraries, and the entailed performance overhead. The paper provides a detailed description of the implementation of the selected approach and a discussion of the lessons we learned from integrating the monitoring in an existing application.

Evolving configurable software poses unique challenges, due to dependencies between the configuration knowledge and the assets that implement the system. Despite a lot of research in the area of configurable software evolution many open challenges subsist, which hamper industrial adoption of different techniques. For instance, there is not much research on the co-evolution of tests and the configuration space. A challenge for this is that the configuration space is often not clearly defined and reasoning over its evolutions and the implication from it is difficult. In this paper, we study the configuration space of the web-based bug tracker Bugzilla, a highly configurable system, replicating the analysis of previous research. In addition, we analyze the evolution of the configuration space over several versions of the system to investigate the changes that were made over the revisions spanning the development of several years and their implications and open challenges.

Software product lines (SPLs) are known for improving productivity and reducing time-to-market through the systematic reuse of assets. SPLs are adopted mainly by re-engineering existing system variants. Feature location techniques (FLTs) support the re-engineering process by mapping the variants’ features to their implementation. However, such FLTs do not perform well when applied to single systems. In this way, there is a lack of FLTs to aid the re-engineering process of a single system into an SPL. In this work, we present a hybrid technique that consists of two complementary types of analysis: i) a dynamic analysis by runtime monitoring traces of scenarios in which features of the system are exercised individually, and ii) a static analysis for refining overlapping traces. We evaluate our technique on three subject systems by computing the common metrics used in FL research. We thus computed Precision, Recall, and F-Score at the line- and method-level of source code. In addition to that, one of the systems has a ground truth available, which we also used for comparing results. Results show that our FLT reached an average of 68-78% precision and 72-81% recall on two systems at the line-level, and 67-65% precision and 68-48% recall at the method-level. In these systems, most of the implementation can be covered by the exercise of the features. For the largest system, our technique reached a precision of up to 99% at the line-level, 94% at the method-level, and 44% when comparing to traces. However, due to its size, it was difficult to reach high code coverage during execution, and thus the recall obtained was on average of 28% at the line-level, 25% at the method-level, and 30% when comparing to traces. The main contribution of this work is a hybrid FLT, its publicly available implementation, and a replication package for comparisons and future studies.

Evidence for umbilical cord blood (UCB) cell therapies as a potential intervention for neurological diseases is emerging. To date, most existing trials worked with allogenic cells, as the collection of autologous UCB from high-risk patients is challenging. In obstetric emergencies the collection cannot be planned. In preterm infants, late cord clamping and anatomic conditions may reduce the availability. The aim of the present study was to assess the feasibility of UCB collection in neonates at increased risk of brain damage. Infants from four high-risk groups were included: newborns with perinatal hypoxemia, gestational age (GA) ≤30 + 0 weeks and/or birthweight 8TNC (range: 0.01–13.0 × 108). TNC and UCB volume correlated significantly with GA. A total of 10.7% (19/177) of included neonates developed brain lesions. To conclude, collection of UCB in neonates at high risk of brain damage is feasible with a multidisciplinary approach and intensive training. High prevalence of brain damage makes UCB collection worthwhile. Collected autologous UCB from mature neonates harbors a sufficient cell count for potential therapy. However, quality and quantity of obtained UCB are critical for potential therapy in preterm infants. Therefore, for extremely preterm infants alternative cell sources such as UCB tissue should be investigated for autologous treatment options because of the low yield of UCB.

Photonic structures can be designed to tailor luminescence properties of materials, which becomes particularly interesting for non-linear phenomena, such as photon upconversion. However, there is no adequate theoretical framework to optimize photonic structure designs for upconversion enhancement. Here, we present a comprehensive theoretical model describing photonic effects on upconversion and confirm the model’s predictions by experimental realization of 1D-photonic upconverter devices with large statistics and parameter scans. The measured upconversion photoluminescence enhancement reaches 82 ± 24% of the simulated enhancement, in the mean of 2480 separate measurements, scanning the irradiance and the excitation wavelength on 40 different sample designs. Additionally, the trends expected from the modeled interaction of photonic energy density enhancement, local density of optical states and internal upconversion dynamics, are clearly validated in all experimentally performed parameter scans. Our simulation tool now opens the possibility of precisely designing photonic structure designs for various upconverting materials and applications., A theoretical framework to optimize photonic structure designs for upconversion enhancement is lacking. Here, the authors present a comprehensive theoretical model and confirm the model’s predictions by experimental realisation of 1D-photonic upconverter devices with large statistics and parameter scans.

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Background/Introduction: Concurrent electroencephalography and resting-state functional magnetic resonance imaging (rsfMRI) have been widely used for studying the (presumably) awake and alert human brain with high temporal/spatial resolution. Although rsfMRI scans are typically collected while individuals are instructed to focus their eyes on a fixated cross, objective and verified experimental measures to quantify degree of vigilance are not readily available. Electroencephalography (EEG) is the modality extensively used for estimating vigilance, especially during eyes-closed resting state. However, pupil size measured using an eye-tracker device could provide an indirect index of vigilance. Methods: Three 12-min resting scans (eyes open, fixating on the cross) were collected from 10 healthy control participants. We simultaneously collected EEG, fMRI, physiological, and eye-tracker data and investigated the correlation between EEG features, pupil size, and heart rate. Furthermore, we used pupil size and EEG features as regressors to find their correlations with blood-oxygen-level-dependent fMRI measures. Results: EEG frontal and occipital beta power (FOBP) correlates with pupil size changes, an indirect index for locus coeruleus activity implicated in vigilance regulation (r = 0.306, p

Traditional routing approaches in VANETs use vehicular to vehicular (V2V) communication. Currently the state of the art shows that using only V2V communication has limitations to face the high mobility and intermittent connections in VANETs. Furthermore, those approaches can be used only in relatively small areas. In this sense, using mobile or fixed nodes to assist the routing process has the potential not only to improve the routing performance, instead to increase the network scalability and access to the cloud and internet. On the other hand, position-based routing has shown to be the most suitable strategy to face the high mobility. This paper, presents a new research direction on 3D-routing for VANETs, in particular, it is focused on position-based routing assisted by mobile or fixed nodes such as Unmanned Aerial Vehicles (UAVs), Road Side Units (RSUs), Mobile Gateways (MGs) or Base Stations (BSs), which perform specific functions to improve the routing performance.

BloodVoyagerS (BVS) is an ns-3 module that simulates the global movement of nanobots in the human body. The Blood-VoyagerS Visualizer (BVS-Vis) is a multi-platform visualization tool for result files of BVS. BVS-Vis shows the distribution of the simulated nanobots over time in a three-dimensional cardiovascular model. The animation can be rotated, moved, zoomed in and it is possible to navigate through different time steps. For a quick interpretation of simulation results, a heat map of the nanobots concentration can be generated via post-processing. BVS-Vis is available as a website and as a complete docker-compose setup. It increases the workflow with BVS significantly and enables prompt analysis of simulation results.

We present a novel simulation framework bridging the gap between in-body nano communication and out-of-body body area network (BAN). We assume nanobots freely flowing within the blood system. Their mobility can be modeled using the BloodVoyagerS module. The communication channels are modeled using proximity (nanobot to nanobot), proximity and ultrasonic communication (nanobot to a gateway), and standard IEEE 802.15.4 for BAN communication. In our simulation framework, we rely on ns-3 to model all the three independent communication channels to, for the first time, study the end-to-end communication performance from nanobots to a connected host system. We consider the system a fundamental basis for more advanced studies of such integrated and very heterogeneous communication systems.

Extracorporeal lung support (ECLS) represents an essential support tool especially for critically ill patients undergoing thoracic surgical procedures. Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we report the efficacy of veno-venous ECLS (VV ECLS) as a bridge to or through LVRS in patients with end-stage lung emphysema and severe hypercapnia. Between January 2016 and May 2017, 125 patients with end-stage lung emphysema undergoing LVRS were prospectively enrolled into this study. Patients with severe hypercapnia caused by chronic respiratory failure were bridged to or through LVRS with low-flow VV ECLS (65 patients, group 1). Patients with preoperative normocapnia served as a control group (60 patients, group 2). In group 1, VV ECLS was implemented preoperatively in five patients and in 60 patients intraoperatively. Extracorporeal lung support was continued postoperatively in all 65 patients. Mean length of postoperative VV ECLS support was 3 ± 1 day. The 90 day mortality rate was 7.8% in group 1 compared with 5% in group 2 (p = 0.5). Postoperatively, a significant improvement was observed in quality of life, exercise capacity, and dyspnea symptoms in both groups. VV ECLS in patients with severe hypercapnia undergoing LVRS is an effective and well-tolerated treatment option. In particular, it increases the intraoperative safety, supports de-escalation of ventilatory strategies, and reduces the rate of postoperative complications in a cohort of patients considered "high risk" for LVRS in the current literature.

Highlights • Several countries affected by medicine shortages reacted by implementing measures. • Several new measures were introduced in 2020, particularly in COVID-19 times. • Nearly all countries use registers which help to prepare and react. • Measures aim to protect national markets. • Solutions at European level are yet to be implemented., Shortages of medicines have become a major public health challenge. The aim of this study was to survey national measures to manage and combat these shortages. A questionnaire survey was conducted with public authorities involved in the Pharmaceutical Pricing and Reimbursement Information (PPRI) network. Reponses relating to measures as of March / April 2020 were received from 24 countries (22 European countries, Canada and Israel). In 20 countries, manufacturers are requested to notify – usually on an obligatory basis – upcoming and existing shortages, which are recorded in a register. Further measures include a regular dialogue with relevant stakeholders (18 countries), financial sanctions for manufacturers in cases of non-supply and/or non-compliance with reporting or stocking requirements (15 countries) and simplified regulatory procedures (20 countries). For defined medicines, supply reserves have been established (14 countries), and legal provisions allow the issuing of export bans (10 countries). Some measures have been introduced since the end of 2019 and countries are planning and discussing further action. While governments reacted by taking national measures, the COVID-19 crisis might serve as an opportunity to join forces in cross-country collaboration and develop joint (e.g. European) solutions to address the shortage issue in a sustainable manner. A practical first step could be to work on a harmonisation of the national registers.

Lanthanide (Ln3+)-based nanoparticles (NPs) with light emission in the ultraviolet (UV), visible, and near-infrared (NIR) region under NIR excitation are emerging multifunctional players in the biomedical field. Excitation and emission wavelengths matching the NIR biological transparency windows (700-1870 nm) set the basis for deeper penetration depth into biological tissues due to less absorption, higher resolution as a result of reduced scattering, and improved imaging contrast due to tissue autofluorescence minimization; all being inevitable requirements for optical in vivo bioimaging. Moreover, frequency-conversion in Ln3+-based NPs is sensitive to their thermal environment, thus allowing for application as optical temperature sensors. Additional heating capability opens the pathway to self-monitored optical agents with potential for photothermal therapies (PTTs). UV-visible emitting upconverting nanoparticles (UCNPs) are of particular interest for applications in photodynamic therapies (PDTs) owing to their capability to trigger various photochemical processes upon NIR excitation. It is the aim of this review to highlight the most recent achievements and advances in the field of Ln3+-based NPs as frequency-converting materials for biomedical applications and to identify current trends as well as remaining challenges. Special focus will be set on the most recently presented Ln3+-based systems whose potential has been evaluated in vitro and in vivo as NIR-to-NIR bioimaging probes, NIR-operating nanothermometers and -heaters as well as photochemical agents.

Background High morbidity and mortality are frequently reported in intensive care patients suffering from severe sepsis with systemic inflammation. With the development of severe respiratory failure, extracorporeal membrane oxygenation (ECMO) is often required. In this study, cytokine adsorption therapy in combination with ECMO is applied in patients with acute respiratory distress syndrome (ARDS) due to severe pneumogenic sepsis. The efficacy of this therapy is evaluated compared with a historical cohort without hemoadsorption therapy. Methods Between January and May 2018, combined high-flow venovenous ECMO and CytoSorb therapy (CytoSorb filter connected to ECMO circuit) was applied in patients (n = 13) with pneumogenic sepsis and ARDS. These patients were prospectively included (CytoSorb group). Data from patients (n = 7) with pneumogenic sepsis and ECMO therapy were retrospectively analyzed (control group). Results All patients survived in the CytoSorb group, where the 30-day mortality rate reached 57% in the control group. After CytoSorb therapy, we instantly observed a significant reduction in procalcitonin (PCT) and C-reactive protein (CRP) levels compared with the control group. Within 48 hours, the initial high doses of catecholamine could be weaned off only in the CytoSorb group. Conclusions Our results indicate that CytoSorb in combination with ECMO is an effective therapy to prevent escalation of sepsis with rapid weaning off high-dose catecholamine infusions and quick reduction in PCT and CRP levels. Optimal timing of immunomodulatory therapy and impact on ECMO-related inflammation still need to be furtherly investigated.

Traditional Wireless Sensor Networks (WSNs) are single-channel based and mainly focus on energy-efficiency and scalability. Therefore, they may readily suffer from issues such as bandwidth insufficiency, interference, jamming and so on. With the deployment of dense sensor networks and the outset of multimedia technology, the intensity of the above-mentioned issues is further aggravated. To address those challenges, the researchers have employed multichannel technology in WSNs that focuses on increasing bandwidth/throughput while decreasing collision/congestion, delay, and energy consumption. For ascertaining a comprehensive exploration of multichannel technology in WSNs, this paper discusses in detail the important issues that are indispensable for providing high-performance and achieving Quality of Service (QoS) in multichannel WSNs. Further on, it evaluates a variety of multichannel MAC protocols under the stated design issues and classifies them into the categories Highly, Medium and Least-Robust, based upon aggregate-of-the-design-issues addressed by the corresponding multichannel MAC protocols for WSNs. Besides on the basis of channel access mechanism, each main category is sub-categorized into Time Division Multiple Access (TDMA), Carrier Sense Multiple Access (CSMA), Composite and Other-Novel classes whereby the functionality of the MAC protocols belonging to each class is briefly discussed along with relevant pros & cons. In addition to that, the survey delineates the implementation of the multichannel methodology in the emerging smart technologies of WSNs. In the end, future research directions are anticipated and a reasonable conclusion is put forth.

ZusammenfassungDie extrakorporale Lungenunterstützung (ECLS) stellt heutzutage ein gut etabliertes Verfahren in der Thoraxchirurgie dar. In Abhängigkeit von der respiratorischen und hämodynamischen Situation des Patienten wird die ECLS in verschiedenen Modalitäten eingesetzt. Dies erfordert ein ausreichendes Wissen über die verschiedene ECMO-Modalitäten (ECMO: extrakorporale Membranoxygenierung), Kanülierungswege, zur Verfügung stehendes technisches Equipment und über die pathophysiologischen Grundlagen im Zusammenhang mit derartiger Technologie, um das individuell auf die Patientenbedürfnisse angepasste Verfahren zu wählen. Dementsprechend kann die Therapie je nach klinischer Situation im Verlauf eskaliert bzw. deeskaliert werden.

Upconversion of low-energy photons into higher energy photons is a non-linear effect that can be strongly enhanced by increasing the intensity of impinging light. Such an enhanced intensity can also be achieved by near-field optical effects in photonic structures. In this paper, we investigate photonic structures in the form of linear gratings with varying periods realised in poly-methyl-methacrylate (PMMA) layers using soft stamps in a thermal nanoimprint process. Master structures were fabricated using e-beam lithography and reactive ion etching in silicon. These master structures were replicated into bi-layer polydimethylsiloxane (PDMS) stamps. PMMA layers with embedded β-NaYF4:25% Er3 + upconverter nanoparticles were applied to glass substrates using spin coating. The PDMS stamps were used to imprint the PMMA layer with very accurate pattern fidelity. The upconversion luminescence around 980 nm was enhanced more than three times by the photonic structure under 1523 nm laser excitation with 0.43 ± 0.02 W/cm2 irradiance, in comparison to a reference sample containing the same amount of upconverter material.

Zusammenfassung Hintergrund Die chirurgische Therapie persistierender bronchopleuraler Fisteln (BPF) kann sich insbesondere aufgrund von rezidivierenden Infekten langwierig gestalten. Als Alternative zur chirurgischen Versorgung steht die intrabronchiale Ventilimplantation zur Verfügung. Hier werden unsere Erfahrungen mit dem Einsatz intrabronchialer Ventilen bei Hochrisikopatienten mit persistierender BPF dargestellt. Material und Methoden Von April 2015 bis März 2017 wurden bei insgesamt 8 Patienten (n = 4 weiblich) mit komplikativem Pleuraempyem und begleitender Lungendestruktion, die eine persistierende BPF entwickelt hatten, intrabronchiale Ventile eingebracht. Die persistierende BPF konnte sowohl bronchoskopisch als auch CT-grafisch dargestellt werden. Die Ventile wurden via flexibler Bronchoskopie eingebracht. Bei n = 6 Patienten wurde aufgrund wiederholter Keimnachweise und persistierenden Infekten ein temporäres Thorakostoma angelegt. Ergebnisse Das mittlere Alter betrug 61 Jahre (45 – 85 Jahre). In allen Fällen konnte die BPF mit intrabronchialen Ventilen okkludiert werden. Nach erfolgreicher Infektsanierung wurden alle Thorakostomata verschlossen. Bei 1 Patientin musste eine Thorakoplastik durchgeführt werden. Zur Therapie der persistierenden BPFs wurden durchschnittlich n = 3 Ventile platziert (1 – 4 Ventile). Bei allen Patienten verlief die Ventilplatzierung komplikationsfrei. Thoraxdrainagen konnten bei ausbleibender Luftfistelung und radiologisch kompletter Entfaltung der Lunge nach durchschnittlich 7 Tagen (3 – 15 Tagen) entfernt werden. Der mittlere Krankenhausaufenthalt nach Ventilimplantation lag bei 10 Tagen (5 – 20 Tagen). Komplikationen traten auch in der Nachbeobachtung nicht auf. Bei 2 Patienten wurden die Ventile bereits nach 6 Monaten entfernt. Die nachfolgenden Kontrollen zeigten weiterhin eine komplette Entfaltung der Lunge. Alle Patienten leben bis dato. Schlussfolgerung Die intrabronchiale Ventilimplantation ist ein sicheres und wirksames Verfahren zur Behandlung von Patienten mit persistierender BPF auf dem Boden von rezidivierenden thorakalen Infekten mit begleitender Lungendestruktion. Insbesondere bei Patienten mit hohem operativem Risiko kann diese Therapie als Alternative zur chirurgischen Intervention mehr in Betracht gezogen werden.

Multi-channel based routing approach may utilize more than one channel for communication and has the ability to provide high performance by more rigorously countering interference, collisions and re-transmissions than the single-channel routing methodology. This research work aims to establish guidelines for future research and development in the area of Wireless Sensor Networks (WSNs) based on the critical analysis of the prevalent multi-channel based routing protocols for WSNs. Due to extensive ongoing research in this domain, a significant number of multi-channel routing strategies have been presented which need to be discussed. To explore, this work not only reviews a variety of single/multi-path and single/multi-radio multichannel routing protocols for WSNs under a novel taxonomy, but also outlines their relevant pros and cons. In order to help design new multi-channel routing strategies for WSNs, an insightful review on the applications, current design issues and associated challenges of multichannel routing in WSNs are in-depth scrutinized. Towards the end, some prospect trends are put forth regarding multi-channel routing for WSNs which may provide a road map for future investigation.

Component-based software development (CBSD) is one of the main programming paradigms of the last decades. The main idea of CBSD is to modularize a system as a configuration of multiple interacting components. Components interact with each other via dedicated component interfaces hiding a component's implementation and making components interchangeable. In this paper, we present an early investigation of unit testing practices of open source component-based software systems with the goal to find out how component-based software systems are actually tested and how to improve unit testing practices as part of future research. Our preliminary results show that unit tests typically directly test the component implementation and not dedicated component APIs. The method coverage of component APIs varied between 17% and 34% in the analyzed projects.

Software testing helps developers to identify bugs. However, awareness of bugs is only the first step. Finding and correcting the faulty program components is equally hard and essential for high-quality software. Fault localization automatically pinpoints the location of an existing bug in a program. It is a hard problem, and existing methods are not yet precise enough for widespread industrial adoption. We propose fault localization via Probabilistic Software Modeling (PSM). PSM analyzes the structure and behavior of a program and synthesizes a network of Probabilistic Models (PMs). Each PM models a method with its inputs and outputs and is capable of evaluating the likelihood of runtime data. We use this likelihood evaluation to find fault locations and their impact on dependent code elements. Results indicate that PSM is a robust framework for accurate fault localization., 4 pages, 3 figures, 2 tables, 3rd Workshop on Validation, Analysis and Evolution of Software Tests

We synthesized and characterized a core-shell-shell upconverting nanoparticle architecture. Compared to the traditional core-shell architecture, we demonstrated 2-fold brighter single particle emission and 8-fold improved emission enhancement via Förster resonant energy transfer to a dye.

Upconverting nanoparticles provide valuable benefits as optical probes for bioimaging and Förster resonant energy transfer (FRET) due to their high signal-to-noise ratio, photostability, and biocompatibility; yet, making nanoparticles small yields a significant decay in brightness due to increased surface quenching. Approaches to improve the brightness of UCNPs exist but often require increased nanoparticle size. Here we present a unique core–shell–shell nanoparticle architecture for small (sub-20 nm), bright upconversion with several key features: (1) maximal sensitizer concentration in the core for high near-infrared absorption, (2) efficient energy transfer between core and interior shell for strong emission, and (3) emitter localization near the nanoparticle surface for efficient FRET. This architecture consists of β-NaYbF(4) (core) @NaY(0.8–x)Er(x)Gd(0.2)F(4) (interior shell) @NaY(0.8)Gd(0.2)F(4) (exterior shell), where sensitizer and emitter ions are partitioned into core and interior shell, respectively. Emitter concentration is varied (x = 1, 2, 5, 10, 20, 50, and 80%) to investigate influence on single particle brightness, upconversion quantum yield, decay lifetimes, and FRET coupling. We compare these seven samples with the field-standard core–shell architecture of βNaY(0.58)Gd(0.2)Yb(0.2)Er(0.02)F(4) (core) @NaY(0.8)Gd(0.2)F(4) (shell), with sensitizer and emitter ions codoped in the core. At a single particle level, the core–shell–shell design was up to 2-fold brighter than the standard core–shell design. Further, by coupling a fluorescent dye to the surface of the two different architectures, we demonstrated up to 8-fold improved emission enhancement with the core–shell–shell compared to the core–shell design. We show how, given proper consideration for emitter concentration, we can design a unique nanoparticle architecture to yield comparable or improved brightness and FRET coupling within a small volume.

Introduction: Small cell lung cancer makes up about 15 percent of all lung cancers. Extensive stage small cell lung cancer (ES-SCLC) carries a poor prognosis, and the thoracic progression is common. It is usually an aggressive cancer that tends to grow and spread quickly. Because of this, surgery is useful for very few patients with small cell lung cancer. Most people with limited-stage small cell lung cancer are treated with chemotherapy in combination with radiation therapy. Method: From 2010 to 2018 9 patients with SCLC very limited Disease was studied. From those there were 5 male with 67 and 4 female with 68 average years. In 3 patients we found stage IA1, one patient with stage IA2, one with IB, two with IIA and 2 patients with stage IIB. From 27 patients from 2010 to 2018 with limited disease there were 12 female (59 average years), 15 male with (68 average years). From those we found 7 patients with stage IIIA, 18 with stage IIIB and two with stage IIIC. The median survival time of patients with SCLC limited disease without OP was 29 months. The median survival time of 6 studied patients with SCLC limited disease with neoadjuvant chemotherapy with carboplatin and etoposide with and without combined radiotherapy and Follow up staging was 103 months. Discussion: Neoadjuvant chemotherapy with and without radiotherapy can significantly expand the median survival time of patients with SCLC limited disease. Further studies are needed with larger patient collective.

Dealing with highly configurable systems is generally very complex. Hundreds of different analysis techniques have been conceived to deal with different aspects of configurable systems. One large focal point is the testing of configurable software. This is challenging due to the large number of possible configurations and because tests themselves are rarely configurable and instead built for specific configurations. Existing tests can usually not be reused on other configurations. Therefore, tests need to be adapted for the specific configuration they are supposed to test. In this paper we report on an experiment about reusing tests in a configurable system. We used manually developed tests for specific configurations of Bugzilla and investigated which of them could be reused for other configurations. Moreover, we automatically generated new test variants (by automatically reusing from existing ones) for combinations of previous configurations. Our results showed that we can directly reuse some tests for configurations which they were not intended for. Nonetheless, our automatically generated test variants generally yielded better results. When applying original tests to new configurations we found an average success rate for the tests of 81,84%. In contrast, our generated test variants achieved an average success rate of 98,72%. This is an increase of 16,88%.

International audience; Most engineering tools do not provide much support for collaborating teams and today's engineering knowledge repositories lack flexibility and are limited. Engineering teams have different needs and their team members have different preferences on how and when to collaborate. These needs may depend on the individual work style, the role an engineer has, and the tasks they have to perform within the collaborating group. However, individual collaboration is insufficient and engineers need to collaborate in groups. This work presents a collaboration framework for collaborating groups capable of providing synchronous and asynchronous mode of collaboration. Additionally, our approach enables engineers to mix these collaboration modes to meet the preferences of individual group members. We evaluate the scalability of this framework using four real life large collaboration projects. These projects were found from GitHub and they were under active development by the time of evaluation. We have tested our approach creating groups of different sizes for each project. The results showed that our approach scales to support every case for the groups created. Additionally, we scouted the literature and discovered studies that support the usefulness of different groups with collaboration styles.

INTRODUCTION: Muscle mass has been shown to be a prognostic marker in patients with liver cirrhosis. Transversal psoas muscle thickness normalized by height (TPMT/height) obtained by routine computed tomography is a simple surrogate parameter for sarcopenia. TPMT/height, however, is not sex specific, which might play a role in risk stratification. Its association with acute-on-chronic liver failure (ACLF) has not been established yet. ACLF is associated with systemic inflammatory dysregulation. This study aimed at evaluating the role of sarcopenia in ACLF development of patients with decompensated cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS) using sex-specific TPMT/height. METHODS: One hundred eighty-six patients from the prospective Non-invasive Evaluation Program for TIPS and Follow Up Network cohort (observational, real-world TIPS cohort with structured follow-up) were analyzed. TPMT/height was measured from routine computed tomography. The sex-specific cutoff was determined to classify patients as sarcopenic and nonsarcopenic for 1-year mortality after TIPS. Clinical outcome was compared. Primary end points were ACLF and 1-year mortality after TIPS. Secondary end points were development of decompensations (hepatic encephalopathy and ascites) after TIPS. RESULTS: The sex-specific cutoff increases the diagnostic accuracy with regard to primary and secondary end points compared with the unisex cutoff. Sex-specific sarcopenia classification is an independent predictor of 1-year mortality and ACLF development in patients with cirrhosis receiving TIPS. Patients in the sarcopenia group showed significantly higher rates of mortality, ascites, overt hepatic encephalopathy, and ACLF after TIPS compared with the nonsarcopenia group. The Chronic Liver Failure Consortium Acute Decompensation score as a marker of systemic inflammation was significantly higher in sarcopenic patients. CONCLUSIONS: This study demonstrates for the first time that sarcopenia is related to ACLF development and systemic inflammation. The prognostic value of TPMT/height can be improved by using sex-specific cutoffs. ClinicalTrials.gov identifier: NCT03584204.

Purpose To systematically analyze risk factors for complications of in-bore transrectal MRI-guided prostate biopsies (MRGB). Materials and methods 90 patients, who were scheduled for MRGB were included for this study. Exclusion criteria were coagulation disorders, therapy with anticoagulant drugs, and acute infections of the urinary and the lower gastrointestinal tract. Directly after, one week and one year after the biopsy, we assessed biopsy related complications (e.g. hemorrhages or signs of prostatitis). Differences between patients with and without complications were analyzed regarding possible risk factors: age, prostate volume, number of taken samples, biopsy duration, biopsy of more than one lesion, diabetes, arterial hypertension, hemorrhoids, benign prostate hyperplasia, carcinoma or prostatitis (according to histopathological analysis), and lesion localization. Complications were classified according to the Clavien-Dindo classification. Results We observed 15 grade I complications in 90 biopsies (16.7%) with slight hematuria in 9 cases (10%), minor vasovagal reactions in 4 cases (4.4%), and urinary retention and positioning-related facial dysesthesia in 1 case each (1.1%). One patient showed acute prostatitis requiring antibiotics as the only grade II complication (1.1%). There were no adverse events that occurred later than one week. Complications grade III or higher such as pelvic abscesses, urosepsis or severe hemorrhages were not seen. There were no significant associations between the assessed risk factors and biopsy-related complications. Conclusion In-bore transrectal MRI-guided prostate biopsies can be considered safe procedures in the diagnosis of prostate cancer with very low complication rates. There seem to be no risk factors for complications.

Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we first describe the application of low-flow venovenous extracorporeal CO2 removal (LFVV-ECCO2R) as bridge to LVRS in patients with end-stage lung emphysema experiencing severe hypercapnia caused by acute failure of the breathing pump. Between March and October 2015, n = 4 patients received single-site LFVV-ECCO2R as bridge to LVRS. Indication for extracorporeal lung support was severe hypercapnia with respiratory acidosis and acute breathing pump failure. Two patients required continuous mechanical ventilation over a temporary tracheostomy and were bed ridden. The other two patients were nearly immobile because of severe dyspnea at rest. Length of preoperative ECCO2R was 14 (1-42) days. All patients underwent unilateral LVRS. Anatomical resection of the right (n = 3) or left (n = 1) upper lobe was performed. Postoperatively, both patients with previous mechanical ventilatory support were successfully weaned. ECCO2R in patients with end-stage lung emphysema experiencing severe hypercapnia caused by acute breathing pump failure is a safe and effective bridging tool to LVRS. In such patients, radical surgery leads to a significant improvement of the performance status and furthermore facilitates respiratory weaning from mechanical ventilation.

Lanthanide-doped nanocrystals are of particular interest for the research community not only due to their ability to shape light by downshifting, quantum cutting, and upconversion but also because novel optical properties can be found by the precise engineering of core–shell nanocrystals. Because of the large surface area-to-volume ratio of nanocrystals, the luminescence is typically suppressed by surface quenching. Here, we demonstrate a mechanism that exploits surface quenching processes to improve the luminescence of our core–shell lanthanide-doped nanocrystals. By carefully tuning the shell thickness of inert β-NaLuF4 around β-NaYF4 nanocrystals doped with Yb3+ and Er3+, we unravel the relationship between quantum yield and shell thickness, and quantify surface quenching rates for the relevant Er3+ and Yb3+ energy levels. This enhanced understanding of the system’s dynamics allowed us to design nanocrystals with a surface quenching-assisted mechanism for bright NIR to NIR downshifting with a distincti...

Lanthanide-based upconverting nanoparticles exhibit significant promise for solar energy generation, biological imaging, and security technologies but have not seen widespread adoption due to the prohibitively low efficiencies of current materials. Weak transition dipole moments between 4f orbitals hinder both photon absorption and emission. Here, we introduce a novel way to increase the radiative transition rates in Yb,Er-based upconverting nanoparticles based on local symmetry distortion. Beginning from a host matrix of the well-studied hexagonal (β)-phase NaYF4, we incrementally remove Y3+ ions and cosubstitute for them a 1:1 mixture of Gd3+ and Lu3+. These two ions act to expand and contract the lattice, respectively, inducing local-level distortion while maintaining the average host structure. We synthesize a range of β-NaY0.8–2xGdxLuxF4:Yb0.18Er0.02 nanoparticles and experimentally confirm that particle size, phase, global structure, and Yb3+ and Er3+ concentrations remain constant as x is varied. U...

To determine if prostate cancer (PCa) and prostatitis can be differentiated by using PI-RADS.3T MR images of 68 patients with 85 cancer suspicious lesions were analyzed. The findings were correlated with histopathology. T2w imaging (T2WI), diffusion weighted imaging (DWI), dynamic contrast enhancement (DCE), and MR-Spectroscopy (MRS) were acquired. Every lesion was given a single PI-RADS score for each parameter, as well as a sum score and a PI-RADS v2 score. Furthermore, T2-morphology, ADC-value, perfusion type, citrate/choline-level, and localization were evaluated.44 of 85 lesions showed PCa (51.8%), 21 chronic prostatitis (24.7%), and 20 other benign tissue such as hyperplasia or fibromuscular tissue (23.5%). The single PI-RADS score for T2WI, DWI, DCE, as well as the aggregated score including and not including MRS, and the PI-RADS v2-score were all significantly higher for PCa than for prostatitis or other tissue (p0.001). The single PI-RADS score for MRS and the PI-RADS sum score including MRS were significantly higher for prostatitis than for other tissue (p=0.029 and p=0.020), whereas the other parameters were not different. Prostatitis usually presented borderline pathological PI-RADS scores, showed restricted diffusion with ADC≥900mm(2)/s in 100% of cases, was more often indistinctly hypointense on T2WI (66.7%), and localized in the transitional zone (57.1%). An ADC≥900mm(2)/s achieved the highest predictive value for prostatitis (AUC=0.859).Prostatitis can be differentiated from PCa using PI-RADS, since all available parameters are more distinct in cases of cancer. However, there is significant overlap between prostatitis and other benign findings, thus PI-RADS is only suitable to a limited extent for the primary assessment of prostatitis. Restricted diffusion with ADC≥900mm(2)/s is believed to be a good indicator for prostatitis. MRS can help to distinguish between prostatitis and other tissue.

Considering both channel quality and stability may enhance the likelihood of optimum channel decision for stream-based communication. Good quality stable channels may maintain a particular quality level during data stream transmission and thereby minimize channel switching overheads such as switching delay, energy consumption, and the associated data loss. Among the published multichannel MAC protocols for WSNs, only a few consider channel quality before assigning wireless channels. Whereas to the best of our knowledge, only few contemplates both channel quality and stability during stream-based communication, however, not very suitable for varying (noisy) environment. To bridge this gap, this work proposes a novel dynamic Multichannel Adaptive approach for Grading Immediate Channels (MAGIC). The MAGIC protocol may predict and classify the available channels under channel quality and stability assessment methodology and determines Local Preferred Channels (LPCs) in a noisy environment. Afterwards, the best among those channels may be selected (under some QoS criteria) for stream-based communication in WSNs. The proposed MAGIC algorithm minimizes channel processing overheads by considering only non-blacklisted channels during a communication session. Simulation results show that the MAGIC algorithm achieves better performance than the counterparts in terms of channel switching delay, energy consumption, and the associated throughput loss.

Mental mapping is a method of interpreting with conceptual metaphors. This method is applied to the admiration song in Song of Songs 7:2–7. The song is interpreted in the context of a dance. For the purpose of interpretation, ancient Egyptian dance paintings and love poems are taken into account. The interpretation presents a methodological study that unmasks arbitrary exegesis and implausible interpretations. It discovers its subtle conceptual metaphors and shows a strategy for a comprehensible exegesis. As a side effect, the male chauvinism present in this song is deconstructed.

We investigate photonic effects of optimized 1D photonic structures on embedded upconverting core-shell nanoparticle layers in a thorough comparison of simulation and experiment regarding parameters relevant for photovoltaic applications.

Unlike the scalar data (such as temperature, pressure and humidity), the vector data (such as image, audio and video) necessitates more stringent Quality of Service (QoS) requirements in terms of bandwidth, delay, reliability and information security. These QoS requirements can be hardly achieved in a proper fashion by using a single channel for wireless communication. However, multichannel methodology may assist in accomplishing these QoS requirements by making possible parallel communication, enhancing throughput/delivery ratio, reducing transmission delay and countering jamming attacks. Furthermore, enabling data gathering at multiple points (i.e. multisink approach) may improve QoS by handling congestion, avoiding single point of failure issue and making possible load balancing between the available routes towards the corresponding destinations. To achieve reliable communication in stream based multichannel Wireless Sensor Networks (WSNs), this work proposes a novel QoS-aware Cross-layered Multichannel Multisink Routing protocol (QCM2R) for WSNs. For substantiating the performance of QCM2R protocol, the simulations are performed in NS-2 demonstrating the performance superiority of the proposed QCM2R protocol against the counterpart in terms of network lifetime, reliability, delay and throughput.

The development of future network architectures and of wireless devices needs to take the challenges in developing region into account. The unexpectedly intermittent connections due to sparse deployment, dynamic topology, or node mobility create a new challenge environment that has not been tackled before in both wired and wireless networks. Many developing regions’ network infrastructures have a lack of a reliable connectivity, such as frequent packet losses and bit errors due to low-quality hardware, and frequent network disconnections. Delay Tolerant Networks were developed to be used as an advanced step towards building a future reliable interplanetary Internet. It has shown significant potential for building systems to deliver public services to remote parts of developing countries. Most of the current work has focused on the problem of message delivery within a single region with the same network infrastructure and namespace. However, many deployments in developing countries will probably involve routing between multiple regions, based on technologies such as WiMAX, Satellites or Ad-hoc networks with short-range radio devices, as in the case of mobile phones with Bluetooth interface. In this paper, we consider the design and implementation of an infrastructure based solutions that effectively handle the intermittent connection in DTNs, for a scenario with hybrid DTN and infrastructure networks (HIDTN) which employs the global handover technologies to manage the performance of developing regions’ network infrastructures.

Robust and effective support for the detection and management of software features and their interactions is crucial for many development tasks but has proven to be an elusive goal despite extensive research on the subject. This is especially challenging for variable systems where multiple variants of a system and their features must be collectively considered. Here an important issue is the typically large number of feature interactions that can occur in variable systems. We propose a method that computes, from a set of known source code level interactions of n features, the relevant interactions involving n+1 features. Our method is based on the insight that, if a set of features interact, it is much more likely that these features also interact with additional features, as opposed to completely different features interacting. This key insight enables us to drastically prune the space of potential feature interactions to those that will have a true impact at source code level. This substantial space reduction can be leveraged by analysis techniques that are based on feature interactions (e.g Combinatorial Interaction Testing). Our observation is based on eight variable systems, implemented in Java and C, totaling over nine million LoC, with over seven thousand feature interactions.