Clinical development of new drug-radiotherapy combinations.

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group's consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer.National Institute for Health ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/nrclinonc.2016.7

The fifteenth data release of the Sloan Digital Sky Surveys : first release of MaNGA derived quantities, data visualization tools and stellar library

Twenty years have passed since first light for the Sloan Digital SkySurvey (SDSS). Here, we release data taken by the fourth phase of SDSS(SDSS-IV) across its first three years of operation (July 2014-July2017). This is the third data release for SDSS-IV, and the fifteenth from SDSS (Data Release Fifteen; DR15). New data come from MaNGA - we release 4824 datacubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g. stellar and gas kinematics, emission line, andother maps) from the MaNGA Data Analysis Pipeline (DAP), and a new data visualisation and access tool we call "Marvin". The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials and examples of data use. While SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V(2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.Publisher PDFPeer reviewe

Galaxy Zoo: CANDELS Barred Disks and Bar Fractions

The formation of bars in disk galaxies is a tracer of the dynamical maturity of the population. Previous studies have found that the incidence of bars in disks decreases from the local Universe to z ~ 1, and by z > 1 simulations predict that bar features in dynamically mature disks should be extremely rare. Here we report the discovery of strong barred structures in massive disk galaxies at z ~ 1.5 in deep rest-frame optical images from CANDELS. From within a sample of 876 disk galaxies identified by visual classification in Galaxy Zoo, we identify 123 barred galaxies. Selecting a sub-sample within the same region of the evolving galaxy luminosity function (brighter than L*), we find that the bar fraction across the redshift range 0.5< z < 2 (f_bar = 10.7 +6.3 -3.5% after correcting for incompleteness) does not significantly evolve. We discuss the implications of this discovery in the context of existing simulations and our current understanding of the way disk galaxies have evolved over the last 11 billion years

Galaxy Zoo: Quantitative Visual Morphological Classifications for 48,000 galaxies from CANDELS

We present quantified visual morphologies of approximately 48 000 galaxies observed in three Hubble Space Telescope legacy fields by the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) and classified by participants in the Galaxy Zoo project. 90 per cent of galaxies have z ≤ 3 and are observed in rest-frame optical wavelengths by CANDELS. Each galaxy received an average of 40 independent classifications, which we combine into detailed morphological information on galaxy features such as clumpiness, bar instabilities, spiral structure, and merger and tidal signatures. We apply a consensus-based classifier weighting method that preserves classifier independence while effectively down-weighting significantly outlying classifications. After analysing the effect of varying image depth on reported classifications, we also provide depth-corrected classifications which both preserve the information in the deepest observations and also enable the use of classifications at comparable depths across the full survey. Comparing the Galaxy Zoo classifications to previous classifications of the same galaxies shows very good agreement; for some applications, the high number of independent classifications provided by Galaxy Zoo provides an advantage in selecting galaxies with a particular morphological profile, while in others the combination of Galaxy Zoo with other classifications is a more promising approach than using any one method alone. We combine the Galaxy Zoo classifications of ‘smooth’ galaxies with parametric morphologies to select a sample of featureless discs at 1 ≤ z ≤ 3, which may represent a dynamically warmer progenitor population to the settled disc galaxies seen at later epochs

Searching for (Dynamic) Principles of Learning

International audienceIn order to provide a comprehensive and predictive framework for learning and memory, a dynamical pattern theory seeks for very general laws and principles that determine stability and change of behavioral patterns. In the nineties, learning was defined as the emergence of a new stable behavioral pattern involving the alteration of the entire layer of underlying dynamics. Twelve years after, we attempt to evaluate what new insights this approach may afford. After a brief outline of a dynamic theory of learning, we propose three generic principles underlying learning, coming from an overview of experimental work on bimanual coordination and pattern perception: a principle of symmetry conservation, a principle of distance, and a principle of time scales. Throughout this first round of research, a deep question lingers as to the possible existence of two routes to learning. Future research has to establish whether they correspond to two levels of behavioral organization, a metric and a topological level, discerned by Bernstein

Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome

Item does not contain fulltextThe exon-junction complex (EJC) performs essential RNA processing tasks. Here, we describe the first human disorder, thrombocytopenia with absent radii (TAR), caused by deficiency in one of the four EJC subunits. Compound inheritance of a rare null allele and one of two low-frequency SNPs in the regulatory regions of RBM8A, encoding the Y14 subunit of EJC, causes TAR. We found that this inheritance mechanism explained 53 of 55 cases (P < 5 x 10(-228)) of the rare congenital malformation syndrome. Of the 53 cases with this inheritance pattern, 51 carried a submicroscopic deletion of 1q21.1 that has previously been associated with TAR, and two carried a truncation or frameshift null mutation in RBM8A. We show that the two regulatory SNPs result in diminished RBM8A transcription in vitro and that Y14 expression is reduced in platelets from individuals with TAR. Our data implicate Y14 insufficiency and, presumably, an EJC defect as the cause of TAR syndrome

Long-lived connection between southern Siberia and northern Laurentia in the Proterozoic

Precambrian supercontinents Nuna-Columbia (1.7 to 1.3 billion years ago) and Rodinia (1.1 to 0.7 billion years ago) have been proposed. However, the arrangements of crustal blocks within these supercontinents are poorly known. Huge, dominantly basaltic magmatic outpourings and intrusions, covering up to millions of square kilometres, termed Large Igneous Provinces, typically accompany (super) continent breakup, or attempted breakup and offer an important tool for reconstructing supercontinents. Here we focus on the Large Igneous Province record for Siberia and Laurentia, whose relative position in Nuna-Columbia and Rodinia reconstructions is highly controversial. We present precise geochronology—nine U–Pb and six Ar–Ar ages—on dolerite dykes and sills, along with existing dates from the literature, that constrain the timing of emplacement of Large Igneous Province magmatism in southern Siberia and northern Laurentia between 1,900 and 720 million years ago. We identify four robust age matches between the continents 1,870, 1,750, 1,350 and 720 million years ago, as well as several additional approximate age correlations that indicate southern Siberia and northern Laurentia were probably near neighbours for this 1.2-billion-year interval. Our reconstructions provide a framework for evaluating the shared geological, tectonic and metallogenic histories of these continental blocks