Eutectic Growth in Two-Phase Multicomponent Alloys

A theory of two-phase eutectic growth for a multicomponent alloy is presented. This theory employs the thermodynamic equilibrium at the solid/liquid interface and thus makes it possible to use standard CALPHAD databases to determine the effects of multicomponent phase equilibrium on eutectic growth. Using the same hypotheses as the Jackson Hunt theory, we find that the growth law determined for binary alloys in the Jackson Hunt theory can be generalized to systems with N elements. In particular, a new model is derived from this theory for ternary two-phase eutectics. The use of this model to predict the eutectic microstructure of systems is discussed

Community Education Has Promise

Despite discouragement about what a couple of studies reveal about some administrators' views of community education, these authors are optimistic that the concept can help schools cope with today's problems and that, perhaps, it holds the key to positive change.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66904/2/10.1177_019263657505939409.pd

Long-term safety of siltuximab in patients with idiopathic multicentric Castleman disease: a prespecified, open-label, extension analysis of two trials.

BACKGROUND:Siltuximab is recommended by international consensus as a first-line treatment for idiopathic multicentric Castleman disease on the basis of durable efficacy and safety data. This study was done to assess the long-term safety and activity of siltuximab over up to 6 years of treatment. METHODS:This study is a prespecified open-label extension analysis of a phase 1 trial (NCT00412321) and a phase 2 trial (NCT01024036), done at 26 hospitals worldwide. Patients in both studies were at least 18 years old with histologically confirmed, symptomatic Castleman disease. This extension study enrolled 60 patients who completed the previous trials without disease progression on siltuximab. Patients received siltuximab infusions of 11 mg/kg every 3 weeks (which could be extended to 6 weeks) for up to 6 years. Descriptive statistics were used to summarise the data. No formal hypothesis testing was performed. The primary endpoint was the safety of siltuximab, assessed at each dosing cycle. The study was registered with ClinicalTrials.gov, number NCT01400503 and with EudraCT, number 2010-022837-27. FINDINGS:Patient enrolment into the phase 1 trial was from June 20, 2005, to Sept 15, 2009, and enrolment into the phase 2 trial was from Feb 9, 2010, to Feb 3, 2012. Patients were enrolled in this long-term extension from April 1, 2011, to Jan 15, 2014. Median follow-up was 6 years (IQR 5·11-7·76). Median treatment duration, from the beginning of the previous trials to the end of the present study, was 5·5 years (IQR 4·26-7·14). Siltuximab was well tolerated; however, adverse events of grade 3 or worse were reported in 36 (60%) of 60 patients with the most common being hypertension (eight [13%]), fatigue (five [8%]), nausea (four [7%]), neutropenia (four [7%]), and vomiting (three [5%]). 25 (42%) patients reported at least one serious adverse event, which most commonly was an infection (eight [13%]). Only two serious adverse events, polycythaemia and urinary retention, were considered related to siltuximab treatment. 18 patients discontinued before study completion, either to receive siltuximab locally (eight) or because of progressive disease (two), adverse events (two), or other reasons (six). No deaths were reported. INTERPRETATION:These results show that siltuximab is well tolerated long term and provides important evidence for the feasibility of the life-long use required by patients with idiopathic multicentric Castleman disease. FUNDING:Janssen R&D and EUSA Pharma

A quantitative variational phase field framework

The finite solid-liquid interface width in phase field models results in non-equilibrium effects, including solute trapping. Prior phase field modeling has shown that this extra degree of freedom, when compared to sharp-interface models, results in solute trapping that is well captured when realistic parameters, such as interface width, are employed. However, increasing the interface width, which is desirable for computational reasons, leads to artificially enhanced trapping thus making it difficult to model departure from equilibrium quantitatively. In the present work, we develop a variational phase field model with independent kinetic equations for the solid and liquid phases. Separate kinetic equations for the phase concentrations obviate the assumption of point wise equality of diffusion potentials, as is done in previous works. Non-equilibrium effects such as solute trapping, drag and interface kinetics can be introduced in a controlled manner in the present model. In addition, the model parameters can be tuned to obtain ``experimentally-relevant" trapping while using significantly larger interface widths than prior efforts. A comparison with these other phase field models suggests that interface width of about three to twenty-five times larger than current best-in-class models can be employed depending upon the material system at hand leading to a speed-up by a factor of $W^{(d+2)}$, where $W$ and $d$ denote the interface width and spatial dimension, respectively. Finally the capacity to model non-equilibrium phenomena is demonstrated by simulating oscillatory instability leading to the formation of solute bands.Comment: 51 pages, 9 figures, supplemental material

Which smoking cessation interventions work best?

Nicotine replacement therapy (NRT), bupropion, nortriptyline, clonidine, and varenicline are all effective, although insufficient evidence exists to recommend one intervention over another (SOR: A, systematic reviews). Effective nonpharmacologic interventions include brief physician advice and more intensive counseling, such as proactive telephone counseling, group and individual counseling, and use of quit lines (SOR: A, systematic reviews)