Experimental Investigations on Particle Number Emissions from GDI Engines

Diese Dissertation behandelt experimentelle Untersuchungen zur Reduktion von Partikelanzahlemissionen beim Ottomotor mit Direkteinspritzung. Messungen an einem Einzylinder-Forschungsaggregat mit kombiniertem Einsatz von Partikelanzahlmessgerät, Partikelgrößenverteilungsmessung sowie optischer Diagnostik und thermodynamischer Analyse ermöglichen dabei die detaillierte Analyse der Partikelbildung und -oxidation. Hierzu werden zahlreiche optische Diagnosetechniken zur Visualisierung der Gemischbildung (Mie-Streulicht, High-Speed PIV) sowie der Rußbildung und -oxidation (High-Speed Imaging, Lichtleitermesstechnik) eingesetzt. Zunächst werden zwei Injektoren mit unterschiedlichem hydraulischen Durchfluss und identischem Spraytargeting in einer Einspritzdruckkammer charakterisiert und bewertet. Im Fokus der experimentellen Arbeiten am Versuchsmotor steht dann der Betrieb bei erhöhter Motorlast und geringer Motordrehzahl. Hierbei stellen die geringen Strömungsgeschwindigkeiten im Brennraum, bedingt durch die geringe Motordrehzahl, sowie die große eingebrachte Kraftstoffmasse eine zentrale Herausforderung für den Gemischbildungsprozess dar. Einen wesentlichen Teil der Arbeit stellt deshalb die detaillierte Analyse des Gemischbildungsprozesses, welcher als Summe aus Kraftstoffeinbringung, Interaktion der Ladungsbewegung mit dem eingebrachten Kraftstoff sowie der Kraftstoffbeschaffenheit beschrieben werden kann, dar. Maßnahmen zur Optimierung der Gemischbildung und Minimierung der Partikelemissionen werden abgeleitet und bewertet. Neben der gezielten Beeinflussung der Ladungsbewegung durch das Aufprägen einer gerichteten Strömung und der Variation der Ventilöffnungszeitpunkte und -öffnungsverläufe, wird auch die Einspritzung gezielt beeinflusst. Hierzu wird neben einer Reduktion des hydraulischen Durchflusses des Injektors auch eine Erhöhung des Einspritzdruckes auf bis zu 500 bar diskutiert

Determination of the Effective Viscosity of Non-newtonian Fluids Flowing Through Porous Media

When non-Newtonian fluids flow through porous media, the topology of the pore space leads to a broad range of flow velocities and shear rates. Consequently, the local viscosity of the fluid also varies in space with a non-linear dependence on the Darcy velocity. Therefore, an effective viscosity μeff is usually used to describe the flow at the Darcy scale. For most non-Newtonian flows the rheology of the fluid can be described by a (non linear) function of the shear rate. Current approaches estimate the effective viscosity by first calculating an effective shear rate mainly by adopting a power-law model for the rheology and including an empirical correction factor. In a second step this averaged shear rate is used together with the real rheology of the fluid to calculate μeff. In this work, we derive a semi-analytical expression for the local viscosity profile using a Carreau type fluid, which is a more broadly applicable model than the power-law model. By solving the flow equations in a circular cross section of a capillary we are able to calculate the average viscous resistance 〈μ〉 directly as a spatial average of the local viscosity. This approach circumvents the use of classical capillary bundle models and allows to upscale the viscosity distribution in a pore with a mean pore size to the Darcy scale. Different from commonly used capillary bundle models, the presented approach does neither require tortuosity nor permeability as input parameters. Consequently, our model only uses the characteristic length scale of the porous media and does not require empirical coefficients. The comparison of the proposed model with flow cell experiments conducted in a packed bed of monodisperse spherical beads shows, that our approach performs well by only using the physical rheology of the fluid, the porosity and the estimated mean pore size, without the need to determine an effective shear rate. The good agreement of our model with flow experiments and existing models suggests that the mean viscosity 〈μ〉 is a good estimate for the effective Darcy viscosity μeff providing physical insight into upscaling of non-Newtonian flows in porous media

an interim analysis from the prospective GMMG-MM5 trial

We investigated the impact of subcutaneous versus intravenous bortezomib in the MM5 trial of the German-Speaking Myeloma Multicenter Group which compared bortezomib, doxorubicin, and dexamethasone with bortezomib, cyclophosphamide, and dexamethasone induction therapy in newly diagnosed multiple myeloma. Based on data from relapsed myeloma, the route of administration for bortezomib was changed from intravenous to subcutaneous after 314 of 604 patients had been enrolled. We analyzed 598 patients who received at least one dose of trial medication. Adverse events were reported more frequently in patients treated with intravenous bortezomib (intravenous=65%; subcutaneous=56%, P=0.02). Rates of grade 2 or more peripheral neuropathy were higher in patients treated with intravenous bortezomib during the third cycle (intravenous=8%; subcutaneous=2%, P=0.001). Overall response rates were similar in patients treated intravenously or subcutaneously. The presence of International Staging System stage III disease, renal impairment or adverse cytogenetic abnormalities did not have a negative impact on overall response rates in either group. To our knowledge this is the largest study to present data comparing subcutaneous with intravenous bortezomib in newly diagnosed myeloma. We show better tolerance and similar overall response rates for subcutaneous compared to intravenous bortezomib. The clinical trial is registered at eudract.ema.europa.eu as n. 2010-019173-16

Concept of the Munich/Augsburg Consortium Precision in Mental Health for the German Center of Mental Health

The Federal Ministry of Education and Research (BMBF) issued a call for a new nationwide research network on mental disorders, the German Center of Mental Health (DZPG). The Munich/Augsburg consortium was selected to participate as one of six partner sites with its concept “Precision in Mental Health (PriMe): Understanding, predicting, and preventing chronicity.” PriMe bundles interdisciplinary research from the Ludwig-Maximilians-University (LMU), Technical University of Munich (TUM), University of Augsburg (UniA), Helmholtz Center Munich (HMGU), and Max Planck Institute of Psychiatry (MPIP) and has a focus on schizophrenia (SZ), bipolar disorder (BPD), and major depressive disorder (MDD). PriMe takes a longitudinal perspective on these three disorders from the at-risk stage to the first-episode, relapsing, and chronic stages. These disorders pose a major health burden because in up to 50% of patients they cause untreatable residual symptoms, which lead to early social and vocational disability, comorbidities, and excess mortality. PriMe aims at reducing mortality on different levels, e.g., reducing death by psychiatric and somatic comorbidities, and will approach this goal by addressing interdisciplinary and cross-sector approaches across the lifespan. PriMe aims to add a precision medicine framework to the DZPG that will propel deeper understanding, more accurate prediction, and personalized prevention to prevent disease chronicity and mortality across mental illnesses. This framework is structured along the translational chain and will be used by PriMe to innovate the preventive and therapeutic management of SZ, BPD, and MDD from rural to urban areas and from patients in early disease stages to patients with long-term disease courses. Research will build on platforms that include one on model systems, one on the identification and validation of predictive markers, one on the development of novel multimodal treatments, one on the regulation and strengthening of the uptake and dissemination of personalized treatments, and finally one on testing of the clinical effectiveness, utility, and scalability of such personalized treatments. In accordance with the translational chain, PriMe’s expertise includes the ability to integrate understanding of bio-behavioral processes based on innovative models, to translate this knowledge into clinical practice and to promote user participation in mental health research and care

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.</p

Rationale and design of the German-speaking myeloma multicenter group (GMMG) trial HD6: a randomized phase III trial on the effect of elotuzumab in VRD induction/consolidation and lenalidomide maintenance in patients with newly diagnosed myeloma

Background: Despite major advances in therapy, multiple myeloma is still an incurable malignancy in the majority of patients. To increase survival, deeper remissions (i.e. CR) translating into longer PFS need to be achieved. Incorporation of new drugs (i.e. bortezomib and lenalidomide) as induction and maintenance treatment in an intensified treatment concept, including high dose melphalan (200 mg/m2), has resulted in increased CR rates, and is considered the standard of care for younger patients. Elotuzumab in combination with lenalidomide and dexamethasone has given better results as lenalidomide and dexamethasone alone in a phase III trial. The GMMG-HD6 trial will be the first phase III trial investigating the role of elotuzumab in combination with bortezomib, lenalidomide and dexamethasone (VRD) induction/consolidation and lenalidomide maintenance within a high dose concept. Methods: GMMG-HD6 is a randomized, open, multicenter phase III trial. The planned recruitment number is 564 NDMM patients. All patients will receive 4 VRD cycles as induction and undergo peripheral blood stem cell mobilization and harvesting. Thereafter they will be treated with high dose melphalan therapy plus autologous stem cell transplantation followed by 2 cycles of VRD consolidation and lenalidomide maintenance. Patients in arm B1 + B2 will additionally receive elotuzumab in the induction phase, whereas patients in A2 + B2 will be treated with elotuzumab added to consolidation and maintenance. The primary endpoint of the trial is PFS. Secondary objectives and endpoints are OS, CR rates after induction therapy comparing the two arms VRD (A1 + A2) vs VRD + elotuzumab (B1 + B2), CR rates after consolidation treatment, best response to treatment during the study, time to progression (TTP), duration of response (DOR), toxicity and quality of life. Results: Since this is the publication of a study protocol of an ongoing study, no results can be presented. Discussion: This phase III trial is designed to evaluate whether the addition of elotuzumab to an intensified treatment concept with high dose melphalan chemotherapy plus autologous stem cell transplantation and induction, consolidation and maintenance treatment with bortezomib and lenalidomide is able to improve PFS compared to the same concept without elotuzumab. Trial registration: NCT02495922 on June 24th, 2015

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049