Quantification and expert evaluation of evidence for chemopredictive biomarkers to personalize cancer treatment.

Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines. We focused on studies that investigated changes in gene or protein expression as predictors of drug sensitivity or resistance. We considered an evidence framework that ranked studies from high level I evidence for randomized controlled trials to low level IV evidence for pre-clinical studies and patient case studies.We found that further in-depth analysis will be required to explore methodological issues, inconsistencies between studies, and tumor specific effects present even within high evidence level studies. Some of these nuances will lend themselves to automation, others will require manual curation. However, the comprehensive cataloging and analysis of dispersed public data utilizing an evidence framework provides a high level perspective on clinical actionability of these protein biomarkers. This framework and perspective will ultimately facilitate clinical trial design as well as therapeutic decision-making for individual patients

Perfect quantum error correction coding in 24 laser pulses

An efficient coding circuit is given for the perfect quantum error correction of a single qubit against arbitrary 1-qubit errors within a 5 qubit code. The circuit presented employs a double `classical' code, i.e., one for bit flips and one for phase shifts. An implementation of this coding circuit on an ion-trap quantum computer is described that requires 26 laser pulses. A further circuit is presented requiring only 24 laser pulses, making it an efficient protection scheme against arbitrary 1-qubit errors. In addition, the performance of two error correction schemes, one based on the quantum Zeno effect and the other using standard methods, is compared. The quantum Zeno error correction scheme is found to fail completely for a model of noise based on phase-diffusion.Comment: Replacement paper: Lost two laser pulses gained one author; added appendix with circuits easily implementable on an ion-trap compute

A composite HII region luminosity function in H alpha of unprecedented statistical weight

Context. Statistical properties of HII region populations in disk galaxies yield important clues to the physics of massive star formation. Aims. We present a set of HII region catalogues and luminosity functions for a sample of 56 spiral galaxies in order to derive the most general form of their luminosity function. Methods. HII region luminosity functions are derived for individual galaxies which, after photometric calibration, are summed to form a total luminosity function comprising 17,797 HII regions from 53 galaxies. Results. The total luminosity function, above its lower limit of completeness, is clearly best fitted by a double power law with a significantly steeper slope for the high luminosity portion of the function. This change of slope has been reported in the literature for individual galaxies, and occurs at a luminosity of log L = 38.6\pm0.1 (L in erg/s) which has been termed the Stromgren luminosity. A steep fall off in the luminosity function above log L = 40 is also noted, and is related to an upper limit to the luminosities of underlying massive stellar clusters. Detailed data are presented for the individual sample galaxies. Conclusions. The luminosity functions of HII regions in spiral galaxies show a two slope power law behaviour, with a significantly steeper slope for the high luminosity branch. This can be modelled by assuming that the high luminosity regions are density bounded, though the scenario is complicated by the inhomogeneity of the ionized interstellar medium. The break, irrespective of its origin, is of potential use as a distance indicator for disc galaxies.Comment: Accepted for publication as a Letter in Astronomy & Astrophysics. Latex with postscript figures. Online-only tables and figures are included in this preprint. The HII region catalogues for 56 galaxies will be published electronically on the CDS but are available also on request from the author

Stability of undissociated screw dislocations in zinc-blende covalent materials from first principle simulations

The properties of perfect screw dislocations have been investigated for several zinc-blende materials such as diamond, Si, $\beta$-SiC, Ge and GaAs, by performing first principles calculations. For almost all elements, a core configuration belonging to shuffle set planes is favored, in agreement with low temperature experiments. Only for diamond, a glide configuration has the lowest defect energy, thanks to an sp$^2$ hybridization in the core

The kinematics of the quadrupolar nebula M1-75 and the identification of its central star

The link between the shaping of bipolar planetary nebulae and their central stars is still poorly understood. The kinematics and shaping of the multipolar nebula M 1-75 are hereby investigated, and the location and nature of its central star are briefly discussed. Fabry-Perot data from GHaFAS on the WHT sampling the Doppler shift of the [N II] 658.3 nm line are used to study the dynamics of the nebula, by means of a detailed 3-D spatio-kinematical model. Multi-wavelength images and spectra from the WFC and IDS on the INT, and from ACAM on the WHT, allowed us to constrain the parameters of the central star. The two pairs of lobes, angularly separated by ~22 degrees, were ejected simultaneously approx. ~3500-5000 years ago, at the adopted distance range from 3.5 to 5.0 kpc. The larger lobes show evidence of a slight degree of point symmetry. The shaping of the nebula could be explained by wind interaction in a system consisting of a post-AGB star surrounded by a disc warped by radiative instabilities. This requires the system to be a close binary or a single star which engulfed a planet as it died. On the other hand, we present broad- and narrow-band images and a low S/N optical spectrum of the highly-reddened, previously unnoticed star which is likely the nebular progenitor. Its estimated V-I colour allows us to derive a rough estimate of the parameters and nature of the central star.Comment: 8 pages, 6 figures, accepted for publication in Astronomy & Astrophysic

Assessing regional patterns of juvenile salmon growth in the Salish Sea

Early marine juvenile growth in Pacific salmon is generally positively correlated with overall survival to reproductive age. In this study, regional patterns of juvenile salmon growth are being analyzed over a two-year period (2012-2013) in the Salish Sea and surrounding waters to better assess juvenile productivity, via growth, in the Salish Sea and surrounding waters to provide us insight into possible mechanisms regulating survival. Insulin-like growth factor-1 (IGF-1), a hormone used to assess instantaneous growth in fishes, including juvenile salmon, was measured in late June and early July of 2012 and 2013 in the Strait of Georgia, Johnstone Strait, Queen Charlotte Strait, and Puget Sound. Juvenile sockeye (Oncorhynchus nerka) and pink salmon (O. gorbuscha) were collected in 2012, whereas juvenile coho (O. kisutch), Chinook (O. tshawytscha), and chum salmon (O. keta) where obtained in both years. In 2012 IGF-1 levels were highest in pink salmon from the Gulf Islands and Puget Sound; this was a unique pattern among the 5 species of juvenile salmon sampled. Coho salmon IGF-1 levels were highest in samples from the Northern Strait of Georgia. Chinook salmon IGF-1 levels were significantly higher in the Strait of Georgia than Puget Sound. The only regions where IGF-1 values were consistently low for three of the four species were Queen Charlotte Strait and Johnstone Strait. Analyses of 2013 IGF-1 levels (juvenile coho, Chinook, chum and a low number of sockeye) are underway and scheduled plans to obtain samples in late June to early July of 2014 are in place

Operational improvements of long-term predicted ephemerides of the Tracking and Data Relay Satellites (TDRSs)

Tracking and Data Relay Satellite (TDRS) orbit determination and prediction are supported by the Flight Dynamics Facility (FDF) of the Goddard Space Flight Center (GSFC) Flight Dynamics Division (FDD). TDRS System (TDRSS)-user satellites require predicted TDRS ephemerides that are up to 10 weeks in length. Previously, long-term ephemerides generated by the FDF included predictions from the White Sands Complex (WSC), which plans and executes TDRS maneuvers. TDRSs typically have monthly stationkeeping maneuvers, and predicted postmaneuver state vectors are received from WSC up to a month in advance. This paper presents the results of an analysis performed in the FDF to investigate more accurate and economical long-term ephemerides for the TDRSs. As a result of this analysis, two new methods for generating long-term TDRS ephemeris predictions have been implemented by the FDF. The Center-of-Box (COB) method models a TDRS as fixed at the center of its stationkeeping box. Using this method, long-term ephemeris updates are made semiannually instead of weekly. The impulse method is used to model more maneuvers. The impulse method yields better short-term accuracy than the COB method, especially for larger stationkeeping boxes. The accuracy of the impulse method depends primarily on the accuracy of maneuver date forecasting

Thrombosis And Hemostasis Centers Pilot Sites Registry: Thrombophilia Screening In Children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106147/1/jth03026.pd