Turbulent Drag Reduction by Flexible and Rodlike Polymers: Crossover Effects at Small Concentrations

Drag reduction by polymers is bounded between two universal asymptotes, the von-K\'arm\'an log-law of the law and the Maximum Drag Reduction (MDR) asymptote. It is theoretically understood why the MDR asymptote is universal, independent of whether the polymers are flexible or rodlike. The cross-over behavior from the Newtonian von-K\'arm\'an log-law to the MDR is however not universal, showing different characteristics for flexible and rodlike polymers. In this paper we provide a theory for this cross-over phenomenology.Comment: 5 pages, 4 figures, submitted to Physical Review

Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: Bevacizumab in combination with interferon-α2a compared with sunitinib

Background: Bevacizumab plus interferon-α2a (IFN) prolongs progression-free survival to>10 months, which is comparable with sunitinib as first-line treatment of metastatic renal cell carcinoma (RCC). The two regimens have different tolerability profiles; therefore, costs for managing adverse events may be an important factor in selecting therapy.Methods: Costs of managing adverse events affecting patients with metastatic RCC eligible for treatment with bevacizumab plus IFN or sunitinib were evaluated using a linear decision analytical model. Management costs were calculated from the published incidence of adverse events and health-care costs for treating adverse events in the United Kingdom, Germany, France and Italy.Results: Adverse event management costs were higher for sunitinib than for bevacizumab plus IFN. The average cost per patient for the management of grade 3-4 adverse events was markedly lower with bevacizumab plus IFN compared with sunitinib in the United Kingdom (\[euro]1475 vs \[euro]804), Germany (\[euro]1785 vs \[euro]1367), France (\[euro]2590 vs \[euro]1618) and Italy (\[euro]891 vs \[euro]402). The main cost drivers were lymphopaenia, neutropaenia, thrombocytopaenia, leucopaenia and fatigue/asthaenia for sunitinib; and proteinuria, fatigue/asthaenia, bleeding, anaemia and gastrointestinal perforation for bevacizumab plus IFN.Conclusion: The costs of managing adverse events are lower for bevacizumab plus IFN than for sunitinib. The potential for cost savings should be considered when selecting treatments for RCC

Colloquium: Theory of Drag Reduction by Polymers in Wall Bounded Turbulence

The flow of fluids in channels, pipes or ducts, as in any other wall-bounded flow (like water along the hulls of ships or air on airplanes) is hindered by a drag, which increases many-folds when the fluid flow turns from laminar to turbulent. A major technological problem is how to reduce this drag in order to minimize the expense of transporting fluids like oil in pipelines, or to move ships in the ocean. It was discovered in the mid-twentieth century that minute concentrations of polymers can reduce the drag in turbulent flows by up to 80%. While experimental knowledge had accumulated over the years, the fundamental theory of drag reduction by polymers remained elusive for a long time, with arguments raging whether this is a "skin" or a "bulk" effect. In this colloquium review we first summarize the phenomenology of drag reduction by polymers, stressing both its universal and non-universal aspects, and then proceed to review a recent theory that provides a quantitative explanation of all the known phenomenology. We treat both flexible and rod-like polymers, explaining the existence of universal properties like the Maximum Drag Reduction (MDR) asymptote, as well as non-universal cross-over phenomena that depend on the Reynolds number, on the nature of the polymer and on its concentration. Finally we also discuss other agents for drag reduction with a stress on the important example of bubbles.Comment: Invited Colloquium Paper for Reviews of Modern Physics, 24 pages, 18 Figs., submitte

Impact of thixotropy on flow patterns induced in a stirred tank : numerical and experimental studies

Agitation of a thixotropic shear-thinning fluid exhibiting a yield stress is investigated both experimentally and via simulations. Steady-state experiments are conducted at three impeller rotation rates (1, 2 and 8 s−1) for a tank stirred with an axial-impeller and flow-field measurements are made using particle image velocimetry (PIV) measurements. Threedimensional numerical simulations are also performed using the commercial CFD code ANSYS CFX10.0. The viscosity of the suspension is determined experimentally and is modelled using two shear-dependant laws, one of which takes into account the flow instabilities of such fluids at low shear rates. At the highest impeller speed, the flow exhibits the familiar outward pumping action associated with axial-flow impellers. However, as the impeller speed decreases, a cavern is formed around the impeller, the flow generated in the vicinity of the agitator reorganizes and its pumping capacity vanishes. An unusual flow pattern, where the radial velocity dominates, is observed experimentally at the lowest stirring speed. It is found to result from wall slip effects. Using blades with rough surfaces prevents this peculiar behaviour and mainly resolves the discrepancies between the experimental and computational results

Fate of yeast and grape pectic polysaccharides of a young red wine in the cross-flow microfiltration process

Cross-flow microfiltration of a young red wine through a mineral membrane of zirconium oxide (average pore size 0.2 μm) laid over a support of agglomerated microporous carbon reduced by 44 % the concentration of the starting wine in soluble polysaccharides. These carbohydrate polymers were mainly constituted of mannose, arabinose, galactose and galacturonic acid associated with minor amounts of rhamnose, glucose, xylose and fucose. The polysaccharides from starting wine and final permeate were separated by gel filtration on Ultrogel AcA 34 (exclusion limit for globular proteins 750,000) in at least four fractions (I-IV) of respective Kav 0.22, 0.50, 0.75 and 0.90. Each polysaccharidic population contained various proportions of yeast mannans, while grape polysaccharides were unequally distributed, fraction I containing neutral type II arabinogalactans and fractions II to IV being complex mixtures of type II arabinogalactans, arabinans and degraded forms of acidic rhamnogalactumnans (pectins). Losses due to microfiltration were positively correlated to hydrodynamic volume (molecular weight) of molecules: (I) "" 79 %, (II) "" 58 %, (III) "" 38 % and (IV) no loss. Yeast and grape polysaccharides coexisting in a given fraction (having the same Kav) were not equally affected by the microfiltration process, yeast mannans passing preferentially the membrane, while grape polymers were more retained. This differential retention was only observed in fractions of high molecular weights (I and II) and was discussed in relation with possible modifications at the molecular level (size and shape of polysaccharides) occurring in the concentration polarisation layer. Application of a back-flush pulse destined to unplug the membrane resulted in a reenrichment of the permeate in the polysaccharides present in the starting wine at a 82 % level

Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

BACKGROUND: Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. METHODS: Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416). RESULTS: The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6). CONCLUSIONS: Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings

Assessing the application of knowledge in clinical problem-solving:The structured professional reasoning exercise

Introduction: Clinical reasoning is a fundamental and core clinical competence of healthcare professionals. The study aimed to investigate the utility of the Structured Professional Reasoning Exercise (SPRE), a new competence assessment method designed to measure dental students’ clinical reasoning in simulated scenarios, covering the clinical areas of Oral Disease, Primary Dental Care and Restorative Dentistry, Child Dental Health and Dental Practice and Clinical Governance. Materials and Methods: A total of 313 year-5 students sat for the assessment. Students spent 45 minutes assimilating the scenarios, before rotating through four pairs of 39 trained examiners who each independently assessed a single scenario over a ten-minute period, using a structured marking sheet. After the assessment, all students and examiners were invited to complete an anonymous perception questionnaire of the exercise. These questionnaires and the examination scores were statistically analysed. Results and Discussion: Oral Disease showed the lowest scores; Dental Practice and Governance the highest. The overall Intraclass Correlation Coefficient (ICC) was 0.770, whilst examiner training helped to increase the ICC from 0.716 in 2013 to 0.835 in 2014. Exploratory factor analysis revealed one major factor with an eigenvalue of 2.75 (68.8% of total variance). The Generalizability coefficient was consistent at 0.806. A total of 295 students and 32 examiners completed the perception questionnaire. Students’ lowest examination perceptions were an “Unpleasant” and “Unenjoyable” experience, whilst the highest were “Interesting”, “Valuable” and “Important”. The majority of students and examiners reported the assessment as acceptable, fair and valid. Conclusion: The SPRE offers a reliable, valid and acceptable assessment method, provided it comprises at least four scenarios with two independently marking and trained assessors. 3.</p

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer

Background:Sunitinib malate (SUTENT) has promising single-agent activity given on Schedule 4/2 (4 weeks on treatment followed by 2 weeks off treatment) in advanced non-small cell lung cancer (NSCLC).Methods:We examined the activity of sunitinib on a continuous daily dosing (CDD) schedule in an open-label, multicentre phase II study in patients with previously treated, advanced NSCLC. Patients ⩾18 years with stage IIIB/IV NSCLC after failure with platinum-based chemotherapy, received sunitinib 37.5 mg per day. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), 1-year survival rate, and safety.Results:Of 47 patients receiving sunitinib, one patient achieved a confirmed partial response (ORR 2.1% (95% confidence interval (CI) 0.1, 11.3)) and 11 (23.4%) had stable disease (SD) ⩾8 weeks. Five patients had SD>6 months. Median PFS was 11.9 weeks (95% CI 8.6, 14.1) and median OS was 37.1 weeks (95% CI 31.1, 69.7). The 1-year survival probability was 38.4% (95% CI 24.2, 52.5). Treatment was generally well tolerated.Conclusions:The safety profile and time-to-event analyses, albeit relatively low response rate of 2%, suggest single-agent sunitinib on a CDD schedule may be a potential therapeutic agent for patients with advanced, refractory NSCLC

Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma

International audienceBackground: Angiogenesis is essential for tumour growth and metastasis. There are conflicting reports as to whether microvessel density (MVD) using the endothelial marker CD105 (cluster of differentiation molecule 105) in clear-cell renal cell carcinomas (ccRCC) is associated with prognosis. Recently, CD105 has been described as a RCC cancer stem cell marker.Methods: A total of 102 ccRCC were analysed. Representative tumour sections were stained for CD105. Vascularity (endothelial CD105) was quantified by MVD. The immunohistochemistry analysis detected positive (if present) or negative (if absent) CD105 tumoral staining. This retrospective population-based study was evaluated using Kaplan–Meier method, t-test and Cox proportional hazard model.Results: We found that the expression of endothelial CD105 (MVD) negatively correlated with nuclear grade (P<0.001), tumour stage (P<0.001) and Leibovitch score (P<0.001), whereas the expression of tumoral CD105 positively correlated with these three clinicopathological factors (P<0.001). In multivariate analysis, tumoral CD105 was found to be an independent predictor of poor overall survival (P=0.002).Conclusions: We have shown for the first time that tumoral CD105 is an independent predictive marker for death risk and unfavourable prognosis in patients with ccRCC after curative resection