Non-Newtonian turbulent jets at low-Reynolds number

We perform direct numerical simulations of planar jets of non-Newtonian fluids at low Reynolds number, in typical laminar conditions for a Newtonian fluid. We select three different non-Newtonian fluid models characterized by shear-thinning (Carreau), viscoelasticity (Oldroyd-B) and shear-thinning and viscoelasticity together (Giesekus), and perform a thorough analysis of the resulting flow statistics. We observe that, as the Weissenberg number is increased, the jet transitions from a laminar flow at low Weissenberg number, to a turbulent flow at high Weissenberg number. We show that the different non-Newtonian features and their combination give rise to rather different flowing regimes, originating from the competition of viscous, elastic and inertial effects. We observe that both viscoelasticity and shear-thinning can develop the instability and the consequent transition to a turbulent flowing regime; however, the purely viscoelastic Oldroyd-B fluid exhibits the onset of disordered fluid motions at a lower Weissenberg number than what observed for the purely shear-thinning Carreau fluid. When the two effects are both present, an intermediate condition is found, suggesting that, in this case, the shear-thinning feature is acting against the fluid elasticity. Despite the qualitative differences observed in the flowing regime, the bulk statistics, namely the centerline velocity and jet thickness, follow almost the same power-law scalings obtained for laminar and turbulent Newtonian planar jets

Non-Newtonian turbulent jets at low-Reynolds number

We perform direct numerical simulations of planar jets of non-Newtonian fluids at low Reynolds number, in typical laminar conditions for a Newtonian fluid. We select three different non-Newtonian fluid models mainly characterized by shear-thinning (Carreau), viscoelasticity (Oldroyd-B) and shear-thinning and viscoelasticity together (Giesekus), and perform a thorough analysis of the resulting flow statistics. We characterize the fluids using the parameter , defined as the ratio of the relevant non-Newtonian time scale over a flow time scale. We observe that, as is increased, the jet transitions from a laminar flow at low , to a turbulent flow at high . We show that the different non-Newtonian features and their combination give rise to rather different flowing regimes, originating from the competition of viscous, elastic and inertial effects. We observe that both viscoelasticity and shear-thinning can develop the instability and the consequent transition to a turbulent flowing regime; however, the purely viscoelastic Oldroyd-B fluid exhibits the onset of disordered fluid motions at a lower value of than what observed for the purely shear-thinning Carreau fluid. When the two effects are both present, an intermediate condition is found, suggesting that, in this case, the shear-thinning feature is acting against the fluid elasticity. Despite the qualitative differences observed in the flowing regime, the bulk statistics, namely the centerline velocity and jet thickness, follow almost the same power-law scalings obtained for laminar and turbulent Newtonian planar jets. The simulations reported here are, to the best of our knowledge, the first direct numerical simulations showing the appearance of turbulence at low Reynolds number in jets, with the turbulent motions fully induced by the non-Newtonian properties of the fluid, since the Newtonian case at the same Reynolds number is characterized by steady, laminar flow.journal articl

Appropriate administration of Granulocyte-Colony Stimulating Factors

 Chemotherapy-induced febrile neutropenia is a potentially fatal complication of cancer treatment and is also the main reason of dose-reduction and/or delay of chemotherapy regimen. Prophylaxis with G-CSF is applicable to reduce the risk of chemotherapy-induced neutropenia. Two molecules of recombinant G-CSF are available for clinical use: lenograstim, identical to human native G-CSF, that is derived from mammalian cells and filgrastim, different to human native G-CSF, expressed in E coli and commercialized in normal form and pegilated long-acting form. Neutrophil morphology and expected defense functions are modified by treatment with filgrastim, while they are not affected by lenograstim. These functionality differences observed in vitro are recently confirmed in a clinical trial that shows a lower incidence of febrile episodes with lenograstim compared to filgrastim in presence of G-CSF induced neutrophils. The long-term safety of lenograstim was supported by the results of a prospective, longer-term study involving almost 4,000 healthy donors. Another important question is the respect of timing of administration of G-CSF and chemotherapy. Absolutely in no case the plasma concentration of G-CSF is to be detected 48h before to 24h post chemotherapeutic drugs administration. In fact, this combination could result in an increased risk of mielotoxicity and a potential for an increase in sensitivity of rapidly dividing myeloid cells to cytotoxic-mutagenic chemotherapy potential. Lenograstim and filgrastim shows short half-life time, instead pegfilgrastim shows detectable concentrations for 16 days after a single administration. This is important to be considered, in particular in bi-weekly and tri-weekly adjuvant chemotherapy regimens. Anyway, the use of the lowest effective dose for the shortest adequate time of medications ensures the optimal balance among effectiveness, safety and costs of treatments, in a context that takes into account effectiveness and efficiency

Morphology of clean and surfactant-laden droplets in homogeneous isotropic turbulence

We perform direct numerical simulations of surfactant-laden droplets in homogeneous-isotropic turbulence with Taylor Reynolds number $Re_\lambda\approx180$. Effects of surfactant on the droplet and local flow statistics are well approximated using a lower, averaged value of surface tension, allowing us to extend the framework developed by Kolmogorov (1949) and Hinze (1955) for surfactant-free bubbles to surfactant-laden droplets. We find the Kolmogorov-Hinze scale ($d_H$) is indeed a pivotal length scale in the droplets' dynamics, separating the coalescence-dominated and the breakage-dominated regimes in the droplet size distribution. We see that droplets smaller than $d_H$ have spheroid-like shapes, whereas larger droplets have long convoluted filamentous shapes with diameters equal to $d_H$. As a result, droplets smaller than $d_H$ have areas that scale as $d^2$, while larger droplets have areas that scale as $d^3$, where $d$ is the droplet equivalent diameter. We further characterise the filamentous droplets by computing the number of handles (loops of the dispersed phase extending into the carrier phase) and voids (regions of the carrier phase enclosed by the dispersed phase) on each droplet. The number of handles per unit length of filament ($0.06d_H^{-1}$) scales inversely with surface tension, while the number of voids is independent of surface tension. Handles are indeed an unstable feature of the interface and are destroyed by the restoring effect of surface tension, whereas voids can move freely inside the droplets.Comment: 31 pages, 13 figure

Vascular endothelial growth factor promoted endothelial progenitor cell mobilization into the peripheral blood of a patient with POEMS syndrome

We assessed the percentage of endothelial progenitor cells (EPCs) in the peripheral blood of a patient with POEMS with elevated VEGF plasma levels. High VEGF plasma levels were associated with increased EPC concentration and treatment with an anti-VEGF antibody induced a consensual decrease of both parameters. In vitro cultures of the patient BM cells suggested that the stromal compartment could be responsible for VEGF overproduction

Nilotinib: a novel encouraging therapeutic option for chronic myeloid leukemia patients with imatinib resistance or intolerance

Although high rates of complete hematologic and cytogenetic remission have been observed in patients with chronic phase chronic myeloid leukemia (CML) treated with imatinib, a short duration of response with eventual emergence of imatinib resistance has also been reported in a subset of CML patients. The most frequent clinically relevant mechanisms that change imatinib sensitivity in BCR-ABL-transformed cells are mutations within the Abl kinase domain, affecting several of its properties. Crystal structure analysis of the Abl-imatinib complex has proven helpful in identifying potential critical residues that hinder interactions of imatinib with mutated Abl. This has led to the development of a second generation of targeted therapies such as nilotinib and dasatinib, already in phase II clinical trials or SKI-606 and MK-0457 in phase I trials. In this review, we discuss the activity of nilotinib, developed by Novartis using a rational drug design strategy in which imatinib served as the lead compound. Preliminary studies demonstrated that nilotinib has more efficacy than imatinib in inhibiting proliferation of BCR-ABL-dependent cells, a relatively safety profile and clinical efficacy in all phases of CML

A Threefold Dose Intensity Treatment With Ifosfamide, Carboplatin, and Etoposide for Patients With Small Cell Lung Cancer: A Randomized Trial

Background The dose intensity of chemotherapy can be increased to the highest possible level by early administration of multiple and sequential high-dose cycles supported by transfusion with peripheral blood progenitor cells (PBPCs). A randomized trial was performed to test the impact of such dose intensification on the long-term survival of patients with small cell lung cancer (SCLC). Methods Patients who had limited or extensive SCLC with no more than two metastatic sites were randomly assigned to high-dose (High, n = 69) or standard-dose (Std, n = 71) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). High-ICE cycles were supported by transfusion with PBPCs that were collected after two cycles of treatment with epidoxorubicin at 150 mg/m2, paclitaxel at 175 mg/m2, and filgrastim. The primary outcome was 3-year survival. Comparisons between response rates and toxic effects within subgroups (limited or extensive disease, liver metastases or no liver metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, normal or abnormal lactate dehydrogenase levels) were also performed. Results Median relative dose intensity in the High-ICE arm was 293% (range = 174%-392%) of that in the Std-ICE arm. The 3-year survival rates were 18% (95% confidence interval [CI] = 10% to 29%) and 19% (95% CI = 11% to 30%) in the High-ICE and Std-ICE arms, respectively. No differences were observed between the High-ICE and Std-ICE arms in overall response (n = 54 [78%, 95% CI = 67% to 87%] and n = 48 [68%, 95% CI = 55% to 78%], respectively) or complete response (n = 27 [39%, 95% CI = 28% to 52%] and n = 24 [34%, 95% CI = 23% to 46%], respectively). Subgroup analyses showed no benefit for any outcome from High-ICE treatment. Hematologic toxicity was substantial in the Std-ICE arm (grade ≥ 3 neutropenia, n = 49 [70%]; anemia, n = 17 [25%]; thrombopenia, n = 17 [25%]), and three patients (4%) died from toxicity. High-ICE treatment was predictably associated with severe myelosuppression, and five patients (8%) died from toxicity. Conclusions The long-term outcome of SCLC was not improved by raising the dose intensity of ICE chemotherapy by threefol

Alpha-fetoprotein surge following high-dose chemotherapy in germ cell tumours

In patients with non-seminomatous germ cell tumours (NSGCTs) who receive chemotherapy and have residual disease, a persistently elevated serum marker level after induction chemotherapy indicates active and progressive disease. High-dose chemotherapy (HDCT) is the standard treatment for patients with relapsed NSGCT. We present a case of a patient with residual disease from NSGCT who showed an increase in serum alpha-fetoprotein levels after HDCT, mimicking progression. Resection of the mass did not show viable cells in the tumour specimen, thus suggesting that the elevated level of the marker was expression of hepatic reconstitution after drug-induced liver damage. HDCT is increasingly used in cases of relapsed NSGCT, and the possibility of treatment-induced alpha-fetoprotein elevation must be taken into account in patient management. © 2013 Edizioni Scientifiche per l'Informazione su Farmaci e Terapia