RANS and DES Computations for a Wing with Ice Accretion

A computational investigation was performed to assess the effectiveness of Detached Eddy Simulation (DES) as a tool for predicting icing effects. The AVUS code, a public domain flow solver, was employed to compute solutions for an iced wing configuration using DES and steady Reynolds Averaged Navier-Stokes (RANS) equation methodologies. The wing section considered here was a business jet airfoil (GLC305) with a 22.5-minute glaze ice accretion (944-ice shape). The section was extruded to form a rectangular planform. The model was mounted between two walls so no tip effects were considered. The numerical results were validated by comparison with experimental data for the same configuration. The time-averaged DES computations showed some improvement in lift and drag results near stall when compared to steady RANS results. However, comparisons of the flow field details did not show the level of agreement suggested by the integrated quantities. More validation is needed to determine what role DES can play as part of an overall icing effects prediction strategy

A Computational Icing Effects Study for a Three-Dimensional Wing: Comparison with Experimental Data and Investigation of Spanwise Variation

Steady-state solutions of the Reynolds-averaged Navier-Stokes (RANS) equations were computed using the Colbalt flow solver for a constant-section, rectangular wing based on an extruded two-dimensional glaze ice shape. The one equation Spalart-Allmaras turbulence model was used. The results were compared with data obtained from a recent wind tunnel test. Computed results indicate that the steady RANS solutions do not accurately capture the recirculating region downstream of the ice accretion, even after a mesh refinement. The resulting predicted reattachment is farther downstream than indicated by the experimental data. Additionally, the solutions computed on a relatively coarse baseline mesh had detailed flow characteristics that were different from those computed on the refined mesh or the experimental data. Steady RANS solutions were also computed to investigate the effects of spanwise variation in the ice shape. The spanwise variation was obtained via a bleeding function that merged the ice shape with the clean wing using a sinusoidal spanwise variation. For these configurations, the results predicted for the extruded shape provided conservative estimates for the performance degradation of the wing. Additionally, the spanwise variation in the ice shape and the resulting differences in the flow fields did not significantly change the location of the primary reattachment

Amyloidosis and 30-Day Outcomes Among Patients With Heart Failure: A Nationwide Readmissions Database Study.

BackgroundThe burden of amyloidosis among hospitalized patients is increasing over time. However, amyloidosis remains an underdiagnosed cause of heart failure (HF) hospitalization among older adults.ObjectivesWe investigated the prevalence and prognostic implications of amyloidosis among patients hospitalized with HF.MethodsAll hospitalizations for primary diagnosis of HF between January 1, 2010, and August 31, 2015, identified in the Nationwide Readmissions Database were categorized into those with and without a secondary diagnosis of amyloidosis. HF hospitalizations with amyloidosis were then matched in a 3:1 fashion to HF hospitalizations without amyloidosis using the year of admission, discharge quarter, age, sex, and Charlson comorbidity index. Primary outcomes were inpatient mortality and 30-day readmission. Multivariable logistic regression was used to estimate the association between HF with amyloidosis and clinical outcomes.ResultsOf 1,593,360 HF hospitalizations that met inclusion criteria, 2,846 (0.18%) had HF with a secondary diagnosis of amyloidosis and were matched to 8,515 hospitalizations for HF without amyloidosis. Hospitalizations for HF with amyloidosis were associated with higher prevalence of kidney disease (56% vs. 45%), malignancy (20% vs. 4%), and higher inpatient mortality (6% vs. 3%) as compared with HF without amyloidosis. In adjusted analyses, HF with amyloidosis was associated with higher odds of in-hospital mortality (odds ratio: 1.46; 95% confidence interval [CI]: 1.17 to 1.82), 30-day readmission (odds ratio: 1.17; 95% CI: 1.05 to 1.31), and longer mean length of stay (least-squares mean difference: 1.46; 95% CI: 1.12 to 1.80).ConclusionsIn patients hospitalized with decompensated HF, presence of amyloidosis was associated with higher risk of inpatient mortality and 30-day readmission

Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia

Bhatt et al. demonstrate that resistance to BCL-2 and MCL-1 antagonists emerges via selection for reduced mitochondrial apoptotic priming. Rapid measurements of drug-induced apoptotic signaling measured by dynamic BH3 profiling identify targeted agents with in vivo efficacy. BCL-2 and MCL-1 antagonist combinations overcome resistance to either single agent. Acquired resistance to BH3 mimetic antagonists of BCL-2 and MCL-1 is an important clinical problem. Using acute myelogenous leukemia (AML) patient-derived xenograft (PDX) models of acquired resistance to BCL-2 (venetoclax) and MCL-1 (S63845) antagonists, we identify common principles of resistance and persistent vulnerabilities to overcome resistance. BH3 mimetic resistance is characterized by decreased mitochondrial apoptotic priming as measured by BH3 profiling, both in PDX models and human clinical samples, due to alterations in BCL-2 family proteins that vary among cases, but not to acquired mutations in leukemia genes. BCL-2 inhibition drives sequestered pro-apoptotic proteins to MCL-1 and vice versa, explaining why in vivo combinations of BCL-2 and MCL-1 antagonists are more effective when concurrent rather than sequential. Finally, drug-induced mitochondrial priming measured by dynamic BH3 profiling (DBP) identifies drugs that are persistently active in BH3 mimetic-resistant myeloblasts, including FLT-3 inhibitors and SMAC mimetics