Low-Dose Continuous 5-Fluorouracil Combined with Leucovorin, nab-Paclitaxel, Oxaliplatin, and Bevacizumab for Patients with Advanced Pancreatic Cancer: A Retrospective Analysis.

BackgroundContinuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic.ObjectiveIn this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy.Patients and methodsSince July of 2008, we have treated 65 patients with 5FU (180 mg/m2/day × 14 days) via an ambulatory pump. Calcium leucovorin (20 mg/m2 IV), nab-paclitaxel (60 mg/m2) IV as a 30-min infusion, and oxaliplatin (50 mg/m2) IV as a 60-min infusion were given on days 1, 8, and 15. Bevacizumab (5 mg/kg) IV over 30 min was administered on days 1 and 15. Cycles were repeated every 28-35 days. There were 42 women and 23 men, and the median age was 59 years. Forty-six patients had stage IV disease.ResultsThe median survival was 19 months, with 82% of patients surviving 12 months or longer. The overall response rate was 49%. There were 28 patients who had received prior treatment, 15 of whom responded to therapy. Fifty-two patients had elevated CA 19-9 prior to treatment. Of these, 21 patients had 90% or greater reduction in CA 19-9 levels. This cohort had an objective response rate of 71% and a median survival of 27 months. Thirty patients stopped treatment due to disease progression, and an additional 22 stopped because of toxicity. One patient died while on therapy.ConclusionsThis non-gemcitabine-based regimen resulted in higher response rates and better survival than what is commonly observed with therapy given at conventional dosing schedules. Low-dose continuous (metronomic therapy) cytotoxic chemotherapy combined with antiangiogenic therapy is safe and effective

Alignment-Insensitive Lower-Cost Telescope Architecture

This architecture features an active wavefront sensing and control scheme along with methods for measuring the relative positions of the primary to aft optics, such as the secondary mirror, and should enable larger and cheaper telescope architectures needed for future applications. A wavefront source/sensor is placed at the center of curvature of the primary mirror. The system provides continuous light onto a primary mirror that is retro-reflected onto itself. This allows the wavefront controller to constantly update the positions of the primary mirror segments (or deformable mirror actuators). Another function of this innovation involves using a concave mirror on the back of the secondary mirror (or other aft optic) that has the same center-of-curvature location (in defocus) as the primary mirror. The two return beams can be aligned next to each other on a detector, or radially on top of each other. This provides a means with which to measure the relative position of the primary to the secondary (or other aft optics), thus allowing for the removal of misalignment of the center-of-curvature source/sensor (meaning it doesn't need precision placement) and also provides a means with which to monitor the relative alignment over time. This innovation does not require extremely good thermal stability on the primary mirror and can thus be used in any thermal environment and with cheaper materials. In addition to this, the architecture lets one phase (or align) the primary mirror independent of whether a star or scene is in the field. The segmented, spherical primary allows for cost-effective three-meter class (e.g. Midex and Discovery) missions as well as enabling 30-meter telescope solutions that can be manufactured in a reasonable amount of time. The continuous wavefront sensing and control architecture enables missions for low-Earth-orbit

Targeted and all-sky search for nanosecond optical pulses at Harvard-Smithsonian

We have built a system to detect nanosecond pulsed optical signals from a target list of some 10,000 sun-like stars, and have made some 20,000 observations during its two years of operation. A beamsplitter feeds a pair of hybrid avalanche photodetectors at the focal plane of the 1.5m Cassegrain at the Harvard/Smithsonian Oak Ridge Observatory (Agassiz Station), with a coincidence triggering measurement of pulse width and intensity at sub-nanosecond resolution. A flexible web-enabled database, combined with mercifully low background coincidence rates (approximately 1 event per night), makes it easy to sort through far-flung data in search of repeated events from any candidate star. An identical system will soon begin observations, synchronized with ours, at the 0.9m Cassegrain at Princeton University. These will permit unambiguous identification of even a solitary pulse. We are planning an all-sky search for optical pulses, using a dedicated 1.8m f/2.4 spherical glass light bucket and an array of pixelated photomultipliers deployed in a pair of matched focal planes. The sky pixels, 1.5 arcmin square, tessellate a 1.6 by 0.2 degree patch of sky in transit mode, covering the Northern sky in approximately 150 clear nights. Fast custom IC electronics will monitor corresponding pixels for coincident optical pulses of nanosecond timescale, triggering storage of a digitized waveform of the light flash

Majority Dynamics and Aggregation of Information in Social Networks

Consider n individuals who, by popular vote, choose among q >= 2 alternatives, one of which is "better" than the others. Assume that each individual votes independently at random, and that the probability of voting for the better alternative is larger than the probability of voting for any other. It follows from the law of large numbers that a plurality vote among the n individuals would result in the correct outcome, with probability approaching one exponentially quickly as n tends to infinity. Our interest in this paper is in a variant of the process above where, after forming their initial opinions, the voters update their decisions based on some interaction with their neighbors in a social network. Our main example is "majority dynamics", in which each voter adopts the most popular opinion among its friends. The interaction repeats for some number of rounds and is then followed by a population-wide plurality vote. The question we tackle is that of "efficient aggregation of information": in which cases is the better alternative chosen with probability approaching one as n tends to infinity? Conversely, for which sequences of growing graphs does aggregation fail, so that the wrong alternative gets chosen with probability bounded away from zero? We construct a family of examples in which interaction prevents efficient aggregation of information, and give a condition on the social network which ensures that aggregation occurs. For the case of majority dynamics we also investigate the question of unanimity in the limit. In particular, if the voters' social network is an expander graph, we show that if the initial population is sufficiently biased towards a particular alternative then that alternative will eventually become the unanimous preference of the entire population.Comment: 22 page

A NOVEL ANTIBACTERIAL RESIN COMPOSITE CONTAINING QUATERNARY AMMONIUM SALTS

poster abstractObjectives: The objective of this study was to synthesize new quater-nary ammonium bromide (QAB)-containing oligomers, incorporate them to dental resin composites, and evaluate the effects of these new oligo-mers on the mechanical strength and antibacterial activity of the formed composites. Methods: The novel quaternary ammonium bromide (QAB)-containing oligomers were synthesized and applied for developing an an-tibacterial resin composite. Compressive strength (CS) and S. mutans (an oral bacteria strain) viability were used to evaluate the mechanical strength and antibacterial activity of the formed composites. Results: All the QAB-modified resin composites showed significant antibacterial activi-ty and mechanical strength reduction. Increasing chain length and loading significantly enhanced the antibacterial activity but dramatically reduced the CS. The 30-day aging study showed that the incorporation of the QAB accelerated the degradation of the composite, suggesting that the QAB may not be well suitable for development of antibacterial dental resin composites or at least the QAB loading should be well controlled, unlike its use in dental glass-ionomer cements. Conclusions: The work in this study is beneficial and valuable to those who are interested in studying antibacterial dental resin composites

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery