Validierung der Solverimplementierung des hygrothermischen Simulationsprogramms Delphin

Das Simulationsprogramm Delphin ermöglicht die Berechnung des gekoppelten Wärme-, Feuchte-, Luft- und Stofftransports in kapillarporösen Materialien. Die Simulation verwendet ein numerisches Lösungsverfahren für die Differentialgleichungen welche die Transportprozesse beschreiben. Zur Kontrolle der numerischen Fehler sowie der korrekten Implementierung der physikalischen Gleichungen werden Validierungsrechnungen durchgeführt. Dafür werden vordefinierte Testfälle eingegeben, gerechnet und mit Referenzlösungen bzw. den Ergebnissen anderer Simulationsprogramme verglichen. In diesem Artikel werden die Ergebnisse der Validierung der Delphin Versionen 5.6, 5.8, 6.0 und 6.1 zusammengefasst. Es wurden folgende Testfälle gerechnet: HAMSTAD Benchmarks 1 bis 5, DIN EN ISO 10211 Fall 1 und 2, DIN EN 15026 und der Aufsaug-Trocknungs-Test. Die Validierung von Delphin erfolgte hinsichtlich des Wärme-, Feuchte- und Lufttransports bei ein- und zweidimensionalen Problemstellungen. Alle Programmversionen erfüllen die Anforderungen aller Testfälle.:1 Einleitung 1.1 Fehlerquellen bei numerischen Lösungsverfahren 1.2 Validierungssystematik 1.3 Beschreibung der Testfälle 2 Materialgenerierung 2.1 Konstante Speichereigenschaften 2.2 Konstante Transporteigenschaften 2.3 Feuchtespeicherung 2.4 Feuchtetransport 2.5 Wärmeleitung 2.6 Materialdatei 3 HAMSTAD Benchmark 1 3.1 Materialdaten 3.2 Klimadaten und Randbedingungen 3.3 Validierungsrechnung 4 HAMSTAD Benchmark 2 4.1 Materialdaten 4.2 Klimadaten und Randbedingungen 4.3 Validierungsrechnung 5 HAMSTAD Benchmark 3 5.1 Materialdaten 5.2 Klimadaten und Randbedingungen 5.3 Validierungsrechnung 6 HAMSTAD Benchmark 4 6.1 Materialdaten 6.2 Klimadaten und Randbedingungen 6.3 Validierungsrechnung 7 HAMSTAD Benchmark 5 7.1 Materialdaten 7.2 Klimadaten und Randbedingungen 7.3 Validierungsrechnung 8 DIN EN ISO 10211 Fall 1 8.1 Materialdaten 8.2 Klimadaten und Randbedingungen 8.3 Validierungsrechnung 9 DIN EN ISO 10211 Fall 2 9.1 Materialdaten 9.2 Klimadaten und Randbedingungen 9.3 Validierungsrechnung 10 DIN EN 15026 10.1 Materialdaten 10.2 Klimadaten und Randbedingungen 10.3 Validierungsrechnung 11 Aufsaug-Trocknungs-Testfall (Wetting&Drying) 11.1 Materialdaten 11.2 Klimadaten und Randbedingungen 11.3 Validierungsrechnung 12 Zusammenfassun

Infants hospitalized for Bordetella pertussis infection commonly have respiratory viral coinfections

Background: Whether viral coinfections cause more severe disease than Bordetella pertussis (B. pertussis) alone remains unclear. We compared clinical disease severity and sought clinical and demographic differences between infants with B. pertussis infection alone and those with respiratory viral coinfections. We also analyzed how respiratory infections were distributed during the 2 years study. Methods: We enrolled 53 infants with pertussis younger than 180 days (median age 58 days, range 17–109 days, 64. 1% boys), hospitalized in the Pediatric Departments at “Sapienza” University Rome and Bambino Gesù Children’s Hospital from August 2012 to November 2014. We tested in naso-pharyngeal washings B. pertussis and 14 respiratory viruses with real-time reverse-transcriptase-polymerase chain reaction. Clinical data were obtained from hospital records and demographic characteristics collected using a structured questionnaire. Results: 28/53 infants had B. pertussis alone and 25 viral coinfection: 10 human rhinovirus (9 alone and 1 in coinfection with parainfluenza virus), 3 human coronavirus, 2 respiratory syncytial virus. No differences were observed in clinical disease severity between infants with B. pertussis infection alone and those with coinfections. Infants with B. pertussis alone were younger than infants with coinfections, and less often breastfeed at admission. Conclusions: In this descriptive study, no associations between clinical severity and pertussis with or without co-infections were found

Genotype-Specific ECG-Based Risk Stratification Approaches in Patients With Long-QT Syndrome.

Background Congenital long-QT syndrome (LQTS) is a major cause of sudden cardiac death (SCD) in young individuals, calling for sophisticated risk assessment. Risk stratification, however, is challenging as the individual arrhythmic risk varies pronouncedly, even in individuals carrying the same variant. Materials and Methods In this study, we aimed to assess the association of different electrical parameters with the genotype and the symptoms in patients with LQTS. In addition to the heart-rate corrected QT interval (QTc), markers for regional electrical heterogeneity, such as QT dispersion (QTmax-QTmin in all ECG leads) and delta Tpeak/end (Tpeak/end V5 - Tpeak/end V2), were assessed in the 12-lead ECG at rest and during exercise testing. Results QTc at rest was significantly longer in symptomatic than asymptomatic patients with LQT2 (493.4 ms ± 46.5 ms vs. 419.5 ms ± 28.6 ms, p = 0.004), but surprisingly not associated with symptoms in LQT1. In contrast, post-exercise QTc (minute 4 of recovery) was significantly longer in symptomatic than asymptomatic patients with LQT1 (486.5 ms ± 7.0 ms vs. 463.3 ms ± 16.3 ms, p = 0.04), while no such difference was observed in patients with LQT2. Enhanced delta Tpeak/end and QT dispersion were only associated with symptoms in LQT1 (delta Tpeak/end 19.0 ms ± 18.1 ms vs. -4.0 ms ± 4.4 ms, p = 0.02; QT-dispersion: 54.3 ms ± 10.2 ms vs. 31.4 ms ± 10.4 ms, p = 0.01), but not in LQT2. Delta Tpeak/end was particularly discriminative after exercise, where all symptomatic patients with LQT1 had positive and all asymptomatic LQT1 patients had negative values (11.8 ± 7.9 ms vs. -7.5 ± 1.7 ms, p = 0.003). Conclusion Different electrical parameters can distinguish between symptomatic and asymptomatic patients in different genetic forms of LQTS. While the classical "QTc at rest" was only associated with symptoms in LQT2, post-exercise QTc helped distinguish between symptomatic and asymptomatic patients with LQT1. Enhanced regional electrical heterogeneity was only associated with symptoms in LQT1, but not in LQT2. Our findings indicate that genotype-specific risk stratification approaches based on electrical parameters could help to optimize risk assessment in LQTS

Prospects of Bioenergy Cropping Systems for A More Social-Ecologically Sound Bioeconomy

The growing bioeconomy will require a greater supply of biomass in the future for both bioenergy and bio-based products. Today, many bioenergy cropping systems (BCS) are suboptimal due to either social-ecological threats or technical limitations. In addition, the competition for land between bioenergy-crop cultivation, food-crop cultivation, and biodiversity conservation is expected to increase as a result of both continuous world population growth and expected severe climate change effects. This study investigates how BCS can become more social-ecologically sustainable in future. It brings together expert opinions from the fields of agronomy, economics, meteorology, and geography. Potential solutions to the following five main requirements for a more holistically sustainable supply of biomass are summarized: (i) bioenergy-crop cultivation should provide a beneficial social-ecological contribution, such as an increase in both biodiversity and landscape aesthetics, (ii) bioenergy crops should be cultivated on marginal agricultural land so as not to compete with food-crop production, (iii) BCS need to be resilient in the face of projected severe climate change effects, (iv) BCS should foster rural development and support the vast number of small-scale family farmers, managing about 80% of agricultural land and natural resources globally, and (v) bioenergy-crop cultivation must be planned and implemented systematically, using holistic approaches. Further research activities and policy incentives should not only consider the economic potential of bioenergy-crop cultivation, but also aspects of biodiversity, soil fertility, and climate change adaptation specific to site conditions and the given social context. This will help to adapt existing agricultural systems in a changing world and foster the development of a more social-ecologically sustainable bioeconomy

Genotype-Specific ECG-Based Risk Stratification Approaches in Patients With Long-QT Syndrome

BackgroundCongenital long-QT syndrome (LQTS) is a major cause of sudden cardiac death (SCD) in young individuals, calling for sophisticated risk assessment. Risk stratification, however, is challenging as the individual arrhythmic risk varies pronouncedly, even in individuals carrying the same variant.Materials and MethodsIn this study, we aimed to assess the association of different electrical parameters with the genotype and the symptoms in patients with LQTS. In addition to the heart-rate corrected QT interval (QTc), markers for regional electrical heterogeneity, such as QT dispersion (QTmax-QTmin in all ECG leads) and delta Tpeak/end (Tpeak/end V5 – Tpeak/end V2), were assessed in the 12-lead ECG at rest and during exercise testing.ResultsQTc at rest was significantly longer in symptomatic than asymptomatic patients with LQT2 (493.4 ms ± 46.5 ms vs. 419.5 ms ± 28.6 ms, p = 0.004), but surprisingly not associated with symptoms in LQT1. In contrast, post-exercise QTc (minute 4 of recovery) was significantly longer in symptomatic than asymptomatic patients with LQT1 (486.5 ms ± 7.0 ms vs. 463.3 ms ± 16.3 ms, p = 0.04), while no such difference was observed in patients with LQT2. Enhanced delta Tpeak/end and QT dispersion were only associated with symptoms in LQT1 (delta Tpeak/end 19.0 ms ± 18.1 ms vs. −4.0 ms ± 4.4 ms, p = 0.02; QT-dispersion: 54.3 ms ± 10.2 ms vs. 31.4 ms ± 10.4 ms, p = 0.01), but not in LQT2. Delta Tpeak/end was particularly discriminative after exercise, where all symptomatic patients with LQT1 had positive and all asymptomatic LQT1 patients had negative values (11.8 ± 7.9 ms vs. −7.5 ± 1.7 ms, p = 0.003).ConclusionDifferent electrical parameters can distinguish between symptomatic and asymptomatic patients in different genetic forms of LQTS. While the classical “QTc at rest” was only associated with symptoms in LQT2, post-exercise QTc helped distinguish between symptomatic and asymptomatic patients with LQT1. Enhanced regional electrical heterogeneity was only associated with symptoms in LQT1, but not in LQT2. Our findings indicate that genotype-specific risk stratification approaches based on electrical parameters could help to optimize risk assessment in LQTS

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial

Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. Methods/design The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH2O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH2O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. Discussion To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. Trial registration ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1929-0) contains supplementary material, which is available to authorized users

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Ableitung einer analytische Lösung für die Dämpfung einer Temperaturwelle in einem halbunendlichen Bauteil bei Randbedingung 3. Art

Im Folgenden wird die analytische Lösung der eindimensionalen, instationären Wärmeleitungsgleichung mit einer Randbedingung 3. Art gegeben. Die Außentemperatur wird dabei als harmonische Schwingung angenommen. Abhängig von den materialspezifischen Eigenschaften des Bauteils (Wärmeleitfähigkeit, Rohdichte, spezifische Wärmekapazität) kommt es zur Dämpfung und zeitlichen Verschiebung der Temperaturwelle im Bauteil. Die analytische Lösung liefert den raum- und zeitaufgelösten Temperaturverlauf innerhalb des Bauteils. Die analytische Lösung ist primär für die Kalibrierung und Validierung numerischer Approximationsverfahren relevant. Die zeitliche Verfügbarkeit von thermischer Speichermasse ist für die thermische Gebäude- und Raumsimulation von besonderer Wichtigkeit. Daher muss ein numerisches Berechnungsverfahren diese Prozesse gut abbilden können. Die hier gezeigte analytische Lösung kann daher zur Bewertung der Güte der gewählten numerischen Approximation verwendet werden. Zu diesem Zweck werden Ergebnisse beispielhaft für zwei getrennte Konstruktionen angegeben

Validierung der Solverimplementierung des hygrothermischen Simulationsprogramms Delphin

Das Simulationsprogramm Delphin ermöglicht die Berechnung des gekoppelten Wärme-, Feuchte-, Luft- und Stofftransports in kapillarporösen Materialien. Die Simulation verwendet ein numerisches Lösungsverfahren für die Differentialgleichungen welche die Transportprozesse beschreiben. Zur Kontrolle der numerischen Fehler sowie der korrekten Implementierung der physikalischen Gleichungen werden Validierungsrechnungen durchgeführt. Dafür werden vordefinierte Testfälle eingegeben, gerechnet und mit Referenzlösungen bzw. den Ergebnissen anderer Simulationsprogramme verglichen. In diesem Artikel werden die Ergebnisse der Validierung der Delphin Versionen 5.6, 5.8, 6.0 und 6.1 zusammengefasst. Es wurden folgende Testfälle gerechnet: HAMSTAD Benchmarks 1 bis 5, DIN EN ISO 10211 Fall 1 und 2, DIN EN 15026 und der Aufsaug-Trocknungs-Test. Die Validierung von Delphin erfolgte hinsichtlich des Wärme-, Feuchte- und Lufttransports bei ein- und zweidimensionalen Problemstellungen. Alle Programmversionen erfüllen die Anforderungen aller Testfälle.:1 Einleitung 1.1 Fehlerquellen bei numerischen Lösungsverfahren 1.2 Validierungssystematik 1.3 Beschreibung der Testfälle 2 Materialgenerierung 2.1 Konstante Speichereigenschaften 2.2 Konstante Transporteigenschaften 2.3 Feuchtespeicherung 2.4 Feuchtetransport 2.5 Wärmeleitung 2.6 Materialdatei 3 HAMSTAD Benchmark 1 3.1 Materialdaten 3.2 Klimadaten und Randbedingungen 3.3 Validierungsrechnung 4 HAMSTAD Benchmark 2 4.1 Materialdaten 4.2 Klimadaten und Randbedingungen 4.3 Validierungsrechnung 5 HAMSTAD Benchmark 3 5.1 Materialdaten 5.2 Klimadaten und Randbedingungen 5.3 Validierungsrechnung 6 HAMSTAD Benchmark 4 6.1 Materialdaten 6.2 Klimadaten und Randbedingungen 6.3 Validierungsrechnung 7 HAMSTAD Benchmark 5 7.1 Materialdaten 7.2 Klimadaten und Randbedingungen 7.3 Validierungsrechnung 8 DIN EN ISO 10211 Fall 1 8.1 Materialdaten 8.2 Klimadaten und Randbedingungen 8.3 Validierungsrechnung 9 DIN EN ISO 10211 Fall 2 9.1 Materialdaten 9.2 Klimadaten und Randbedingungen 9.3 Validierungsrechnung 10 DIN EN 15026 10.1 Materialdaten 10.2 Klimadaten und Randbedingungen 10.3 Validierungsrechnung 11 Aufsaug-Trocknungs-Testfall (Wetting&Drying) 11.1 Materialdaten 11.2 Klimadaten und Randbedingungen 11.3 Validierungsrechnung 12 Zusammenfassun