Emerging treatment options for BRAF-mutant colorectal cancer.

The personalization of cancer care is rooted in the premise that there are subsets of patients with tumors harboring clinically relevant targets for patient-specific treatments. Colorectal cancer (CRC) is a disease that has historically been notable for its dearth of biomarkers that are predictive of response to targeted therapies. In recent years, BRAFV600E-mutated CRC has emerged as a distinct biologic entity, typically refractory to standard chemotherapy regimens approved for the treatment of metastatic CRC and associated with a dismal prognosis. Multiple clinical trials sought to replicate the successes of targeted therapies seen in BRAFV600E-mutated melanoma without success; metastatic BRAFV600E-mutated CRC is clearly a distinct biologic entity. We review a number of recent studies demonstrating the evidence of modest responses to combinations of BRAF, EGFR, and/or MEK inhibition in patients with metastatic BRAFV600E-mutated CRC; however, despite advances, overall survival remains far inferior for these patients compared to their BRAF-wild-type counterparts. Development of combination therapies to impede signaling through the MAPK pathway through alternate targets remains an area of active investigation. Reflecting the rapid evolution of efforts for this small subset of CRC patients, the first-ever Phase III study is now underway evaluating the combination of BRAF, EGFR, and MEK inhibition. Immunotherapies are also an area of active research, particularly for the subset of patients with tumors that are also microsatellite instability (MSI) high. Here, we summarize the current landscape and emerging data on the molecular, clinical, and therapeutic aspects of BRAF-mutant CRC

Using Text Analysis Tools to Improve Reference FAQs

A team of WSU reference librarians regularly reviews email reference questions and creates online FAQs as an aid to patrons and librarians. In the current project, text analysis tools were used to supplement the traditional process in an attempt to better understand the frequency and context of email reference queries. The presentation provides information on the text analysis tools used in the project, and presents several Q&A pairs developed using this process

Visual Characterisation of Temporal Occupancy for Movement Ecology

Movement ecologists study aspects of animals' movement, behaviour, and the factors that might drive these. Temporal patterns of local occupancy often reveal the type of usage at a location. We present and apply temporal tile-maps that embed temporal visual encodings into cartographic representations, and do so in an interactive visual analysis context. This reveals spatial variation in temporal occupancy that allows places to be identified and distinguished according to their use by animals. We apply these to GPS data from tracking gulls and illustrate the application to movement ecology. The tool that implements this and data are available to download and use

Library inventory using a RFID wand: contribution of tag and book specific factors on the read rate

Purpose Low read rates are a general problem in library inventories. The purpose of this study is to examine the factors that contribute to the success of library inventory by means of a radio-frequency identification (RFID) inventory taker. The factors investigated were tag position, tag orientation, book thickness, tag density (related to thickness of a sequence of books) and position on the shelf. Design/methodology/approach A total of 210 books were placed in eight random permutations on three fixed book shelves. For each configuration, the RFID tags were read forty times. The resulting data were analysed by means of a generalized linear model, relating the combined contribution of tag position, tag orientation, book thickness and position on the bookshelf to the read rate. Findings The tags positioned directly next to the spine were always read, but those near the opening of the book (far from the spine and inventory reader) were not always read. Considering only books with tags near the opening, tag orientation and position on the shelf appeared not to be related to the read rate, while book thickness, thickness over three books and spine tag density appeared to have a small positive contribution to the read rate. Practical implications Low read rates during a library inventory can be prevented by placing the tags near the book spine – the other book specific factors (listed in the previous paragraph) are of little influence. When not scanned during a first sweep, repeated scanning can increase the read rate with 0.15. Originality/value This paper is one of the first to analyse the influence of tag location and book specific factors on the read rate of RFID tags in library books. The experimental approach sets an example for future work

The Prompt Gamma-Ray and Afterglow Energies of Short-Duration Gamma-Ray Bursts

I present an analysis of the gamma-ray and afterglow energies of the complete sample of 17 short duration GRBs with prompt X-ray follow-up. I find that 80% of the bursts exhibit a linear correlation between their gamma-ray fluence and the afterglow X-ray flux normalized to t=1 d, a proxy for the kinetic energy of the blast wave ($F_{X,1}~F_{gamma}^1.01). An even tighter correlation is evident between E_{gamma,iso} and L_{X,1} for the subset of 13 bursts with measured or constrained redshifts. The remaining 20% of the bursts have values of F_{X,1}/F_{gamma} that are suppressed by about three orders of magnitude, likely because of low circumburst densities (Nakar 2007). These results have several important implications: (i) The X-ray luminosity is generally a robust proxy for the blast wave kinetic energy, indicating nu_X>nu_c and hence a circumburst density n>0.05 cm^{-3}; (ii) most short GRBs have a narrow range of gamma-ray efficiency, with ~0.85 and a spread of 0.14 dex; and (iii) the isotropic-equivalent energies span 10^{48}-10^{52} erg. Furthermore, I find tentative evidence for jet collimation in the two bursts with the highest E_{gamma,iso}, perhaps indicative of the same inverse correlation that leads to a narrow distribution of true energies in long GRBs. I find no clear evidence for a relation between the overall energy release and host galaxy type, but a positive correlation with duration may be present, albeit with a large scatter. Finally, I note that the outlier fraction of 20% is similar to the proposed fraction of short GRBs from dynamically-formed neutron star binaries in globular clusters. This scenario may naturally explain the bimodality of the F_{X,1}/F_{gamma} distribution and the low circumburst densities without invoking speculative kick velocities of several hundred km/s.Comment: Submitted to ApJ; 9 pages, 2 figures, 1 tabl

The M33 Variable Star Population Revealed by Spitzer

We analyze five epochs of Spitzer Space Telescope/Infrared Array Camera (IRAC) observations of the nearby spiral galaxy M33. Each epoch covered nearly a square degree at 3.6, 4.5, and 8.0 microns. The point source catalog from the full dataset contains 37,650 stars. The stars have luminosities characteristic of the asymptotic giant branch and can be separated into oxygen-rich and carbon-rich populations by their [3.6] - [4.5] colors. The [3.6] - [8.0] colors indicate that over 80% of the stars detected at 8.0 microns have dust shells. Photometric comparison of epochs using conservative criteria yields a catalog of 2,923 variable stars. These variables are most likely long-period variables amidst an evolved stellar population. At least one-third of the identified carbon stars are variable.Comment: Accepted for publication in ApJ. See published article for full resolution figures and electronic table

Mapping atomic and diffuse interstellar band absorption across the Magellanic Clouds and the Milky Way

Diffuse interstellar bands (DIBs) trace warm neutral and weakly-ionized diffuse interstellar medium (ISM). Here we present a dedicated, high signal-to-noise spectroscopic study of two of the strongest DIBs, at 5780 and 5797 \AA, in optical spectra of 666 early-type stars in the Small and Large Magellanic Clouds, along with measurements of the atomic Na\,{\sc i}\,D and Ca\,{\sc ii}\,K lines. The resulting maps show for the first time the distribution of DIB carriers across large swathes of galaxies, as well as the foreground Milky Way ISM. We confirm the association of the 5797 \AA\ DIB with neutral gas, and the 5780 \AA\ DIB with more translucent gas, generally tracing the star-forming regions within the Magellanic Clouds. Likewise, the Na\,{\sc i}\,D line traces the denser ISM whereas the Ca\,{\sc ii}\,K line traces the more diffuse, warmer gas. The Ca\,{\sc ii}\,K line has an additional component at $\sim200$--220 km s$^{-1}$ seen towards both Magellanic Clouds; this may be associated with a pan-Magellanic halo. Both the atomic lines and DIBs show sub-pc-scale structure in the Galactic foreground absorption; the 5780 and 5797 \AA\ DIBs show very little correlation on these small scales, as do the Ca\,{\sc ii}\,K and Na\,{\sc i}\,D lines. This suggests that good correlations between the 5780 and 5797 \AA\ DIBs, or between Ca\,{\sc ii}\,K and Na\,{\sc i}\,D, arise from the superposition of multiple interstellar structures. Similarity in behaviour between DIBs and Na\,{\sc i} in the SMC, LMC and Milky Way suggests the abundance of DIB carriers scales in proportion to metallicity.Comment: Accepted for publication in MNRA