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"Busch, Daniel"
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Accuracy of hemodynamic parameters derived by GE E-PiCCO in comparison with PiCCO® in patients admitted to the intensive care unit
To evaluate the agreement and accuracy of a novel advanced hemodynamic monitoring (AHM) device, the GE E-PiCCO module, with the well-established PiCCO® device in intensive care patients using pulse contour analysis (PCA) and transpulmonary thermodilution (TPTD). A total of 108 measurements were performed in 15 patients with AHM. Each of the 27 measurement sequences (one to four per patient) consisted of a femoral and a jugular indicator injection via central venous catheters (CVC) and measurement using both PiCCO (PiCCO® Jug and Fem) and GE E-PiCCO (GE E-PiCCO Jug and Fem) devices. For statistical analysis, Bland–Altman plots were used to compare the estimated values derived from both devices. The cardiac index measured via PCA (CIpc) and TPTD (CItd) was the only parameter that fulfilled all a priori-defined criteria based on bias and the limits of agreement (LoA) by the Bland–Altman method as well as the percentage error by Critchley and Critchley for all three comparison pairs (GE E-PiCCO Jug vs. PiCCO® Jug, GE E-PiCCO Fem vs. PiCCO® Fem, and GE E-PiCCO Fem vs. GE E-PiCCO Jug), while the GE E-PiCCO did not accurately estimate EVLWI, SVRI, SVV, and PPV values measured via the jugular and femoral CVC compared with values assessed by PiCCO®. Consequently, measurement discrepancy should be considered on evaluation and interpretation of the hemodynamic status of patients admitted to the ICU when using the GE E-PiCCO module instead of the PiCCO® device.
Journal Article
LLM-based code generation and system migration in language-driven engineering
This paper illustrates the power of extending Language Driven Engineering (LDE) with Domain-Specific Natural Languages (DSNLs) through a case study on two levels. Both cases benefit from the characteristic decomposition feature of LDE, resulting in tasks tailored to the application of domain-specific languages, here with a focus on the application of DSNLs supported by LLM-based code generation. In the first case study, we show how DSNL-supported LDE facilitates the development of point-and-click adventures, whereas the second case study focuses on migration: We demonstrate how the entire LDE scenario for point-and-click adventure games can be migrated to output TypeScript instead of JavaScript using LLM-based code generation exclusively, without manually writing any code. This migration not only infers the required types, but also preserves an important property of the original LDE scenario: generated web applications can be automatically validated by design via automata learning and subsequent model checking. Even better, this property can be exploited to automatically validate the correctness of the migration by learning so-called
difference automata
that characterize the behavioral differences between the generated JavaScript-based and Type-Script-based applications.
Journal Article
Biases in ‘sustainable finance’ metrics could hinder lending to those that need it most
Private-investor approaches for measuring the emissions associated with lending to governments risk creating perverse incentives.
Private-investor approaches for measuring the emissions associated with lending to governments risk creating perverse incentives.
Journal Article
Characterization and first results from LACIS-T: a moist-air wind tunnel to study aerosol–cloud–turbulence interactions
The interactions between turbulence and cloud microphysical processes have been investigated primarily through numerical simulation and field measurements over the last 10 years. However, only in the laboratory we can be confident in our knowledge of initial and boundary conditions and are able to measure under statistically stationary and repeatable conditions. In the scope of this paper, we present a unique turbulent moist-air wind tunnel, called the Turbulent Leipzig Aerosol Cloud Interaction Simulator (LACIS-T) which has been developed at TROPOS in order to study cloud physical processes in general and interactions between turbulence and cloud microphysical processes in particular. The investigations take place under well-defined and reproducible turbulent and thermodynamic conditions covering the temperature range of warm, mixed-phase and cold clouds (25∘C>T>-40∘C). The continuous-flow design of the facility allows for the investigation of processes occurring on small temporal (up to a few seconds) and spatial scales (micrometer to meter scale) and with a Lagrangian perspective. The here-presented experimental studies using LACIS-T are accompanied and complemented by computational fluid dynamics (CFD) simulations which help us to design experiments as well as to interpret experimental results. In this paper, we will present the fundamental operating principle of LACIS-T, the numerical model, and results concerning the thermodynamic and flow conditions prevailing inside the wind tunnel, combining both characterization measurements and numerical simulations. Finally, the first results are depicted from deliquescence and hygroscopic growth as well as droplet activation and growth experiments. We observe clear indications of the effect of turbulence on the investigated microphysical processes.
Journal Article
Protective Role of Peroxisome Proliferator–activated Receptor-β/δ in Septic Shock
Abstract
Rationale
Peroxisome proliferator–activated receptor (PPAR)-β/δ is a transcription factor that belongs to the PPAR nuclear hormone receptor family, but the role of PPAR-β/δ in sepsis is unknown.
Objectives
We investigated the role of PPAR-β/δ in murine models of LPS-induced organ injury and dysfunction and cecal ligation and puncture (CLP)–induced polymicrobial sepsis.
Methods
Wild-type (WT) and PPAR-β/δ knockout (KO) mice and C57BL/6 mice were subjected to LPS for 16 hours. C57BL/6 mice received the PPAR-β/δ agonist GW0742 (0.03 mg/kg intravenously, 1 h after LPS) or GW0742 plus the PPAR-β/δ antagonist GSK0660 (0.1 mg/kg intravenously, 30 min before LPS). CD-1 mice subjected to CLP received GW0742 or GW0742 plus GSK0660.
Measurements and Main Results
In PPAR-β/δ KO mice, endotoxemia exacerbated organ injury and dysfunction (cardiac, renal, and hepatic) and inflammation (lung) compared with WT mice. In C57BL/6 mice subjected to endotoxemia, GW0742 significantly (1) attenuated organ (cardiac and renal) dysfunction and inflammation (lung); (2) increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β; (3) attenuated the increase in extracellular signal-regulated kinase (ERK)1/2 and signal transducer and activator of transcription (STAT)-3 phosphorylation; and (4) attenuated the activation of nuclear factor (NF)-κB and the expression of inducible nitric oxide synthase (iNOS). In CD-1 mice subjected to CLP, GW0742 improved 10-day survival. All the observed beneficial effects of GW0742 were attenuated by the PPAR-β/δ antagonist GSK0660.
Conclusions
PPAR-β/δ protects against multiple organ injury and dysfunction, and inflammation caused by endotoxic shock and improves survival in polymicrobial sepsis by a mechanism that may involve activation of Akt and inhibition of GSK-3β and NF-κB.
Journal Article
Delayed activation of PPAR-β/δ improves long-term survival in mouse sepsis: effects on organ inflammation and coagulation
Activation of peroxisome proliferator-activated receptor (PPAR)-β/δ reduces tissue injury in murine endotoxemia. We hypothesized that the PPAR-β/δ-agonist GW0742 improves long-term outcome after sepsis caused by cecal ligation and puncture (CLP). Fifty-one CD-1 female mice underwent CLP and received either vehicle (control), GW0742 (0.03 mg/kg/injection; five post-CLP i.v. injections), GSK0660 (PPAR-β/δ-antagonist) or both and were monitored for 28 d. Another 20 CLP mice treated with GW0742 and vehicle were sacrificed 24 h post-CLP to assess coagulopathy. Compared to vehicle, survival of CLP-mice treated with GW0742 was higher by 35% at d 7 and by 50% at d 28. CLP mice treated with GW0742 had 60% higher IFN-γ but circulating monocyte chemoattractant protein-1 and chemokine ligand were lower at 48 h post-CLP. Compared to vehicle, CLP mice treated with GW0742 exhibited a 50% reduction in the circulating plasminogen activator inhibitor-1 associated with an increase in platelet number at 24 h post-CLP (but no changes occurred in anti-thrombin-III, plasminogen, fibrinogen and clotting-times). CLP mice treated with GW0742 exhibited a similar increase in most of the biochemical markers of organ injury/dysfunction (lactate dehydrogenase, alanine aminotransferase, creatine kinase, creatinine, blood urea nitrogen, and triglycerides) measured. Treatment with GW0742 consistently improved long-term survival in septic CD-1 mice by partially modulating the post-CLP systemic cytokine response and coagulation systems.
Journal Article
Influence of CD68.sup.+ macrophages and neutrophils on anastomotic healing following laparoscopic sigmoid resection due to diverticulitis
Background The aim of this prospective study was to evaluate the predictive value of a potential preexisting low-grade inflammation regarding the incidence of anastomotic leakage in elective laparoscopic sigmoid resection due to diverticulitis. Methods Patients with either chronically recurrent diverticulitis or sigmoid stenosis caused by chronic diverticulitis were included in this study. All patients with acute local or systemic inflammation were excluded. Detailed patient information (e.g. American Society of Anesthesiologists (ASA) grade, comorbidities, duration of hospital stay, and anastomotic leakage) was prospectively recorded. CD68.sup.+ macrophages, neutrophils, CD3.sup.+ T-lymphocytes, CD11c.sup.+ dendritic cells, MHCII, TNFR1, and NF-[kappa]B were evaluated by immunohistochemistry within the acquired sample of colonic bowel wall tissue. Clinical and immunohistochemical data was compared between groups (leakage vs. no leakage). Additionally, a matched-pair analysis was performed due to the widely heterogeneous groups concerning the number of patients and to minimize the effect of extraneous variables. Results A total of 83 patients were included in the study, of which 7 patients suffered an anastomotic leakage. Neither the clinical nor the immunohistochemical parameters were significantly different between the groups. The matched-pair analysis revealed a nonsignificant increase in mean duration of hospital stay for the group with anastomotic leakage and a significantly higher percentage of CD68.sup.+ macrophages and neutrophils in the colonic wall obtained at the index operation in both the mucosal and submucosal layers for the leakage group. Conclusions A preexisting low-grade inflammation represented by infiltrates of macrophages and neutrophils is a predictor for increased risk of developing colon anastomotic leakage.
Journal Article