222 research outputs found
Vorticity Confinement methods for cavitating flows
Present work deals with investigations of numerical aspects of cavitating vortex dominated flows. Computations of the viscous flow on realistic, technical configurations require efficient methods and high grid resolution, which is not sufficient in most cases to capture important details of the flow. Insufficient resolution increases the numerical dissipation of vortices generated at the tip region of lifting surfaces. One possible solution to reduce the unphysical decay of the strength of the vortices (despite of moderate resolution) is the application of vorticity confinement methods. Aim of the paper is the development and the comparison of Vorticity Confinement (VC) methods for cavitating flows on unstructured grids. Applications are proposed to control devices and marine propulsion systems. The numerical dissipation of vortices is compared for different VC formulations. Especially the influence of the source terms on cavitating flows is investigated. The numerical computations are carried out by the finite volume solution method FreSCo on arbitrary grids. In the study vorticity confinement techniques are combined with different cavitation models available in the applied numerical method to investigate tip vortex flow. The cavitation models are based on Volume-of-Fluid (VoF). A NACA16020 elliptical wing is selected as a validation case. The combination of vorticity confinement formulations and cavitation models enables a better and a more detailed study of cavitation effects.http://deepblue.lib.umich.edu/bitstream/2027.42/84314/1/CAV2009-final139.pd
Implementation of on-site velocity boundary conditions for D3Q19 lattice Boltzmann
On-site boundary conditions are often desired for lattice Boltzmann
simulations of fluid flow in complex geometries such as porous media or
microfluidic devices. The possibility to specify the exact position of the
boundary, independent of other simulation parameters, simplifies the analysis
of the system. For practical applications it should allow to freely specify the
direction of the flux, and it should be straight forward to implement in three
dimensions. Furthermore, especially for parallelized solvers it is of great
advantage if the boundary condition can be applied locally, involving only
information available on the current lattice site. We meet this need by
describing in detail how to transfer the approach suggested by Zou and He to a
D3Q19 lattice. The boundary condition acts locally, is independent of the
details of the relaxation process during collision and contains no artificial
slip. In particular, the case of an on-site no-slip boundary condition is
naturally included. We test the boundary condition in several setups and
confirm that it is capable to accurately model the velocity field up to second
order and does not contain any numerical slip.Comment: 13 pages, 4 figures, revised versio
Quantitative analysis of numerical estimates for the permeability of porous media from lattice-Boltzmann simulations
During the last decade, lattice-Boltzmann (LB) simulations have been improved
to become an efficient tool for determining the permeability of porous media
samples. However, well known improvements of the original algorithm are often
not implemented. These include for example multirelaxation time schemes or
improved boundary conditions, as well as different possibilities to impose a
pressure gradient. This paper shows that a significant difference of the
calculated permeabilities can be found unless one uses a carefully selected
setup. We present a detailed discussion of possible simulation setups and
quantitative studies of the influence of simulation parameters. We illustrate
our results by applying the algorithm to a Fontainebleau sandstone and by
comparing our benchmark studies to other numerical permeability measurements in
the literature.Comment: 14 pages, 11 figure
Evaluation of Euler Fluxes for Hypersonic Flow Computations
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76462/1/AIAA-33735-324.pd
Genotyping and antibiotic resistance of thermophilic Campylobacter isolated from chicken and pig meat in Vietnam
Background Campylobacter species are recognized as the most common cause of
foodborne bacterial gastroenteritis in humans. In this study nine
Campylobacter strains isolated from chicken meat and pork in Hanoi, Vietnam,
were characterized using molecular methods and tested for antibiotic
resistance. Results The nine isolates (eight C. jejuni and one C. coli) were
identified by multiplex PCR, and tested for the presence or absence of 29 gene
loci associated with virulence, lipooligosaccharide (LOS) biosynthesis and
further functions. flaA typing, multilocus sequence typing and microarray
assay investigation showed a high degree of genetic diversity among these
isolates. In all isolates motility genes (flaA, flaB, flhA, fliM),
colonization associated genes (cadF, docB), toxin production genes (cdtA,
cdtB, secD, secF), and the LOS biosynthesis gene pglB were detected. Eight
gene loci (fliY, virB11, Cje1278, Cj1434c, Cj1138, Cj1438c, Cj1440c, Cj1136)
could not be detected by PCR. A differing presence of the gene loci ciaB (22.2
%), Cje1280 (77.8 %), docC (66.7 %), and cgtB (55.6 %) was found. iamA, cdtC,
and the type 6 secretion system were present in all C. jejuni isolates but not
in C. coli. flaA typing resulted in five different genotypes within C. jejuni,
MLST classified the isolates into seven sequence types (ST-5155, ST-6736,
ST-2837, ST-4395, ST-5799, ST-4099 and ST-860). The microarray assay analysis
showed a high genetic diversity within Vietnamese Campylobacter isolates which
resulted in eight different types for C. jejuni. Antibiotic susceptibility
profiles showed that all isolates were sensitive to gentamicin and most
isolates (88.8 %) were sensitive to chloramphenicol, erythromycin and
streptomycin. Resistance rates to nalidixic acid, tetracycline and
ciprofloxacin were 88.9, 77.8 and 66.7 %, respectively. Conclusions To the
best of our knowledge, this study is the first report that shows high genetic
diversity and remarkable antibiotic resistance of Campylobacter strains
isolated from meat in Vietnam which can be considered of high public health
significance. These preliminary data show that large scale screenings are
justified to assess the relevance of Campylobacter infections on human health
in Vietnam
Evaluation of Euler Fluxes for Hypersonic Heating Computations
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83575/1/AIAA-41605-439.pd
Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE):a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network
Background: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. Methods: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II–IV mantle cell lymphoma, aged 18–65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1–5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1–4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1–19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. Findings: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84–92) versus 72% (67–79; hazard ratio 0·52 [one-sided 98·3% CI 0–0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67–79) versus 86% (82–91; hazard ratio 1·77 [one-sided 98·3% CI 0–3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3–5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3–5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). Interpretation: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. Funding: Janssen and Leukemia & Lymphoma Society.</p
Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE):a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network
Background: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. Methods: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II–IV mantle cell lymphoma, aged 18–65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1–5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1–4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1–19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. Findings: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84–92) versus 72% (67–79; hazard ratio 0·52 [one-sided 98·3% CI 0–0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67–79) versus 86% (82–91; hazard ratio 1·77 [one-sided 98·3% CI 0–3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3–5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3–5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). Interpretation: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. Funding: Janssen and Leukemia & Lymphoma Society.</p
Point Mutations in the FLT3-ITD Region Are Rare but Recurrent Alterations in Adult AML and Associated With Concomitant KMT2A-PTD
FLT3-ITD mutations are common druggable alterations in patients with acute myeloid leukemia (AML) and associated with poor prognosis. Beside typical ITD mutations, point mutations and deletions in the juxtamembrane domain (JMD) have been observed. However, due to the low frequency of these alterations, there is only limited information on molecular and clinical associations. To evaluate the prognostic impact of non-ITD mutations in the FLT3 JMD region, we analyzed a large cohort of 1,539 adult AML patients treated in different protocols of the Study Alliance Leukemia, using next-generation sequencing. Non-ITD point mutations and deletions within the FLT3 JMD were identified with a prevalence of ~1.23% (n = 19). Both FLT3-ITD and non-ITD mutations were associated with a higher rate of NPM1 (42%–61%; p < 0.001) and DNMT3A mutations (37%–43%; p < 0.001), as well as an increased percentage of peripheral blood (54%–65%) and bone marrow blast cells (74%; p < 0.001), compared to FLT3-wild-type patients. Most significantly, AML patients with FLT3 non-ITD mutations had a higher rate of concomitant KMT2A-PTD mutations (37.5%; p < 0.001) as compared to FLT3-ITD (7%) or FLT3-wild-type cases (4.5%). In a multivariable analysis, FLT3 non-ITD mutations were not an independent prognostic factor. However, patients with dual FLT3 non-ITD and KMT2A-PTD mutations showed a trend for inferior outcome, which points at a functional interaction in this subset of AML
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