Lagrangian filtered density function for LES-based stochastic modelling of turbulent dispersed flows

The Eulerian-Lagrangian approach based on Large-Eddy Simulation (LES) is one of the most promising and viable numerical tools to study turbulent dispersed flows when the computational cost of Direct Numerical Simulation (DNS) becomes too expensive. The applicability of this approach is however limited if the effects of the Sub-Grid Scales (SGS) of the flow on particle dynamics are neglected. In this paper, we propose to take these effects into account by means of a Lagrangian stochastic SGS model for the equations of particle motion. The model extends to particle-laden flows the velocity-filtered density function method originally developed for reactive flows. The underlying filtered density function is simulated through a Lagrangian Monte Carlo procedure that solves for a set of Stochastic Differential Equations (SDEs) along individual particle trajectories. The resulting model is tested for the reference case of turbulent channel flow, using a hybrid algorithm in which the fluid velocity field is provided by LES and then used to advance the SDEs in time. The model consistency is assessed in the limit of particles with zero inertia, when "duplicate fields" are available from both the Eulerian LES and the Lagrangian tracking. Tests with inertial particles were performed to examine the capability of the model to capture particle preferential concentration and near-wall segregation. Upon comparison with DNS-based statistics, our results show improved accuracy and considerably reduced errors with respect to the case in which no SGS model is used in the equations of particle motion

Phase I/II study of single-agent bortezomib for the treatment of patients with myelofibrosis. Clinical and biological effects of proteasome inhibition.

A phase I/II trial was undertaken to determine maximum tolerated dose (MTD), toxicity, clinical efficacy and biological activity of bortezomib in patients with advanced stage primary or post-polycythemia vera/post-essential thrombocythemia myelofibrosis (MF). Bortezomib (0.8, 1.0, or 1.3 mg/m(2)) was administered on days 1, 4, 8, and 11 by intravenous push to patients previously resistant to at least one line of therapy, or with an intermediate/high risk IWG’s score [1]. Therapy was repeated every 28 days for 6 cycles. At 1.3 mg/m(2) dose, one of six patients experienced a dose limiting toxicity, and this was determined to be the MTD. Neither remissions or clinical improvements were recorded in 16 patients treated at this dose level, fulfilling the early stopping rule in the Simon two-stage study design. Major toxicity was on thrombocytopenia. In 9 out of 15 patients bortezomib proved able to reduce bone marrow vessel density. However, the agent was associated with worsening of markers of disease activity, like enhancement of hematopoietic CD34-positive progenitor cell mobilization, WT-1 gene expression in mononuclear cells, and down-regulation of CXCR4 expression on CD34-positive cells. Occurrence of both beneficial and detrimental biological effects claims further investigation on the mechanisms of the drug in MF

Cardiovascular risk changes after lipid lowering medications: are they predictable?

Abstract Changes in cardiovascular risk after lipid lowering medications are generally expressed as relative risk reduction (RRR). Comparison of the eight major studies published in this last decade indicates that the RRRs ranged from a minimum (19%) for the LRC Study with cholestyramine, to maximal values of 34 -37% for studies such as the HHS, 4S and AFCAPS/TexCAPS. These RRRs were barely related to the drugs' effects on major lipid parameters, e.g. LDL cholesterol. Instead, by using the absolute risk reduction (ARRs), easily calculated by subtracting the percentage end points for the drug treated from these values of the placebo group in all studies, a wide range of values was found, also adding to the series a non pharmacological study such as the Program on the Surgical Control of the Hyperlipidemias (POSCH) trial. Calculated ARRs were directly correlated to the baseline cardiovascular (CV) risk in all studies, thus allowing an easy prediction of a drug's effect in the selected population. Drugs with different mechanisms (statins, fibrates and resins) all fitted into this correlation nomogram. These findings clearly indicate that the CV effects of lipid changes, such as LDL cholesterol and triglyceride reduction or HDL rises, are in the same direction, and can be well predicted. The similar, almost identical behavior of drugs affecting LDL cholesterolemia to a different degree or not at all, indicates that novel approaches should be sought to improve risk reduction and that individual therapy should be ideally pursued, rather than a 'one drug' approach

The treatment of polycythaemia vera: an update in the JAK2 era

The clinical course of polycythaemia vera is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukaemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, with the drug of choice being hydroxyurea because its leukaemogenicity is low. The recent discovery of JAK2 V617F mutation in the vast majority of polycythaemia vera patients opens new avenues for the treatment of this disease. Novel therapeutic options theoretically devoid of leukaemic risk, such as alpha-interferon and imatinib, affect JAK2 expression in some patients. Nevertheless, these drugs require further clinical experience and, for the time being, should be reserved for selected cases

Disponibilidad eólica en Los Varela - Dpto. Ambato - Catamarca

En este trabajo se describen las características principales del recurso eólico en la región centro-norte del valle de la Subcuenca del Río Los Puestos, a partir de los registros sistemáticos de velocidad y dirección del viento, por un período de 24 meses consecutivos, en la Estación registradora instalada en Los Varela - Dpto. Ambato - Catamarca. Los datos procesados estadísticamente brindan información respecto a la distribución de frecuencias de velocidad, las velocidades clasificadas y las calmas clasificadas, siempre a partir de sus posibilidades de aprovechamiento a nivel de máquinas lentas y de turbinas rápidas. También se muestran los valores de potencia en Kw.h/m² distribuidos mensualmente. En síntesis podemos decir que se descarta la posibilidad de acceder a grandes aprovechamientos a partir de turbinas rápidas, pues los valores medios de velocidad no alcanzan los mínimos requeridos para ese tipo de máquinas. En cambio tienen muy buenas posibilidades las máquinas lentas como los molinos americanos para bombeo de agua y los pequeños generadores eléctricos para bajo consumo, pues existe una buena distribución mensual y anual, con valores de velocidad bastante aceptables.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Plasma Phospholipid Omega‐3 Fatty Acids and Incidence of Postoperative Atrial Fibrillation in the OPERA Trial

Background: Long‐chain polyunsaturated omega‐3 fatty acids (n‐3 PUFA) demonstrated antiarrhythmic potential in experimental studies. In a large multinational randomized trial (OPERA), perioperative fish oil supplementation did not reduce the risk of postoperative atrial fibrillation (PoAF) in cardiac surgery patients. However, whether presupplementation habitual plasma phospholipid n‐3 PUFA, or achieved or change in n‐3 PUFA level postsupplementation are associated with lower risk of PoAF is unknown. Methods and Results: In 564 subjects undergoing cardiac surgery between August 2010 and June 2012 in 28 centers across 3 countries, plasma phospholipid levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were measured at enrollment and again on the morning of cardiac surgery following fish oil or placebo supplementation (10 g over 3 to 5 days, or 8 g over 2 days). The primary endpoint was incident PoAF lasting ≥30 seconds, centrally adjudicated, and confirmed by rhythm strip or ECG. Secondary endpoints included sustained (≥1 hour), symptomatic, or treated PoAF; the time to first PoAF; and the number of PoAF episodes per patient. PoAF outcomes were assessed until hospital discharge or postoperative day 10, whichever occurred first. Relative to the baseline, fish oil supplementation increased phospholipid concentrations of EPA (+142%), DPA (+13%), and DHA (+22%) (P<0.001 each). Substantial interindividual variability was observed for change in total n‐3 PUFA (range=−0.7% to 7.5% after 5 days of supplementation). Neither individual nor total circulating n‐3 PUFA levels at enrollment, morning of surgery, or change between these time points were associated with risk of PoAF. The multivariable‐adjusted OR (95% CI) across increasing quartiles of total n‐3 PUFA at enrollment were 1.0, 1.06 (0.60 to 1.90), 1.35 (0.76 to 2.38), and 1.19 (0.64 to 2.20); and for changes in n‐3 PUFA between enrollment and the morning of surgery were 1.0, 0.78 (0.44 to 1.39), 0.89 (0.51 to 1.55), and 1.01 (0.58 to 1.75). In stratified analysis, demographic, medication, and cardiac parameters did not significantly modify these associations. Findings were similar for secondary PoAF endpoints. Conclusions: Among patients undergoing cardiac surgery, neither higher habitual circulating n‐3 PUFA levels, nor achieved levels or changes following short‐term fish oil supplementation are associated with risk of PoAF. Clinical Trial Registration URL: Clinicaltrials.gov Unique identifier: NCT0097048

Results of Phase II Clinical Trial MPD-RC 101: Allogeneic Hematopoietic Stem Cell Transplantation Conditioned with Fludarabine/Melphalan in Patients with Myelofibrosis

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Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

&lt;p&gt;Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.&lt;/p&gt; &lt;p&gt;Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (&#60;2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).&lt;/p&gt; &lt;p&gt;Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).&lt;/p&gt