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

Sunitinib and other targeted therapies for renal cell carcinoma

Targeted therapy has radically altered the way metastatic renal cancer is treated. Six drugs are now licensed in this setting, with several other agents under evaluation. Sunitinib is currently the most widely used in the first line setting with impressive efficacy and an established toxicity profile. However, as further randomised studies report and as newer drugs become available this may change. In this review, we address our current understanding of targeted therapy in renal cancer. We also discuss areas in which our knowledge is incomplete, including the identification of correlative biomarkers and mechanisms of drug resistance. Finally, we will describe the major areas of clinical research that will report over the next few years

Outcome of minimally invasive management of salivary calculi in 4,691 patients

Objective: To evaluate the application of minimally invasive techniques in the management of salivary stones. Background: The incidence of salivary calculi is 60 cases/million/year, with most stones situated in the mid or proximal duct. The current treatment of these stones is adenectomy. This paper reports the results of minimally invasive methods of stone removal that avoid gland excision. Methods: Observational study of 5,528 consecutive patients treated by lithotripsy, endoscopy, basket retrieval, and/or surgery in five centers from 1990 to 2004 inclusive. A total of 567cases were excluded, leaving 4,691 patients (parotid n=1,165, submandibular n=3,526) for analysis. Results: Salivary calculi were eliminated in 3,775/4,691 (80.5%) of cases and partly cleared in 782/4,691 (16.7%). Salivary glands were removed in 134/4,691 (2.9%) of patients with symptoms in whom treatment failed. Conclusions: Minimally invasive techniques move treatment of salivary calculi to an outpatient or a day case setting. They are reliable ways of both retrieving stones and eliminating symptoms, and mean that the gland rarely has to be removed

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

Reuse of treated wastewater in viticulture: Can it be an alternative source of nutrient-rich water?

Water scarcity is a global problem, which leads to unprecedented pressure on water supply in arid and semi-arid regions. Treating wastewater is an alternative and valuable water resource, therefore its reuse for agricultural irrigation has been growing worldwide since the beginning of the 21st century. In several regions of the wine-producing countries subject to significant water stress (e.g., Australia, California-USA, Spain), wastewater recycling appears to be the most accessible alternative, both financially and technically, for the agricultural uses that notably not requiring drinking water. Therefore, this research was planned to quantify the contribution of treated wastewater (TWW) to fertilization-needs of the vine, evaluate the impact of irrigation with TWW on the soil, vegetative growth, yield, and wine and grape juice composition. The results provide scientific and technical knowledge on a strategy of water management with high added value. The fertilizer contribution of the TWW would be important, according to the plant's nutrient needs (e.g., in this study 19–39 Unit N, 0.5–1.1 Unit P and 14–28 Unit K ha−1 were supplied with TWW). Ensuring treated wastewater microbiological quality is essential, but without reducing of its nutrients. These nutrients would be a valuable input for crop growth and yield, and could reduce the need to resort for inorganic/synthetic fertilizers. A sustainable use of treated wastewater over the long term would, however, necessitate a good practice guidelines and an integrated vision of treated wastewater quality, crops, irrigation and post-harvest practices

Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma

Background Metastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to ≥6 yr. Objective To analyze long-term safety with sunitinib in mRCC patients. Design, setting, and participants Data were pooled from 5739 patients in nine trials, comprising seven phase II studies, a phase III study, and an expanded-access trial in various treatment settings (e.g. cytokine refractory or treatment-naïve). Outcome measurements and statistical analysis Interval and cumulative time-period analyses evaluated the incidence of treatment-related adverse events (TRAEs) for up to 6 yr, in the overall population and in those with long-term (≥2 yr) sunitinib treatment. Results and limitations Among long-term patients (n=807), most TRAEs occurred initially in the first year and then decreased in frequency; TRAEs following this pattern included decreased appetite, diarrhea, dysgeusia, dyspepsia, fatigue, hypertension, mucosal inflammation, nausea, and stomatitis. However, hypothyroidism increased by interval analysis from 6% at 0-<6 mo to 42% at 5-<6 yr and by cumulative analysis from 14% at 0-<1 yr to 36% over 6 yr. Grade 3/4 TRAEs in long-term patients peaked during the first year and then steadily decreased. The overall population displayed only minor differences from long-term patients, with no clinically significant differences between grade ≥3 TRAE profiles (<5% difference in incidence rates at all intervals). Limitations included retrospective design, assessment variability, lack of pharmacokinetic data, and absence of baseline characteristics for long-term patients. Conclusions Prolonged sunitinib was not associated with new types or increased severity of TRAEs. Except hypothyroidism, toxicity was not cumulative. Patient summary More than 800 mRCC patients received sunitinib for between 2 and 6 yr without experiencing new or more severe treatment-related toxicity. Clinicians may be able to prescribe chronic sunitinib treatment for as long as patients continue to derive clinical benefit, without untoward additional risk

Cabozantinib versus everolimus, nivolumab, axitinib, sorafenib and best supportive care: A network meta-analysis of progression-free survival and overall survival in second line treatment of advanced renal cell carcinoma

Background Relative effect of therapies indicated for the treatment of advanced renal cell carcinoma (aRCC) after failure of first line treatment is currently not known. The objective of the present study is to evaluate progression-free survival (PFS) and overall survival (OS) of cabozantinib compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC) in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI) treatment. Methodology & findings Systematic literature search identified 5 studies for inclusion in this analysis. The assessment of the proportional hazard (PH) assumption between the survival curves for different treatment arms in the identified studies showed that survival curves in two of the studies did not fulfil the PH assumption, making comparisons of constant hazard ratios (HRs) inappropriate. Consequently, a parametric survival network meta-analysis model was implemented with five families of functions being jointly fitted in a Bayesian framework to PFS, then OS, data on all treatments. The comparison relied on data digitized from the Kaplan-Meier curves of published studies, except for cabozantinib and its comparator everolimus where patient level data were available. This analysis applied a Bayesian fixed-effects network meta-analysis model to compare PFS and OS of cabozantinib versus its comparators. The log-normal fixed-effects model displayed the best fit of data for both PFS and OS, and showed that patients on cabozantinib had a higher probability of longer PFS and OS than patients exposed to comparators. The survival advantage of cabozantinib increased over time for OS. For PFS the survival advantage reached its maximum at the end of the first year’s treatment and then decreased over time to zero. Conclusion With all five families of distributions, cabozantinib was superior to all its comparators with a higher probability of longer PFS and OS during the analyzed 3 years, except with the Gompertz model, where nivolumab was preferred after 24 months