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Mike Irwin

Bio: Mike Irwin is an academic researcher from University of Cambridge. The author has contributed to research in topics: Galaxy & Milky Way. The author has an hindex of 136, co-authored 755 publications receiving 83262 citations. Previous affiliations of Mike Irwin include University of New South Wales & Lawrence Berkeley National Laboratory.


Papers
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Journal ArticleDOI
TL;DR: A data-driven analysis of computational pathology reveals lymphocyte density as an independent predictor of pCR, a histological indicator of chemotherapy response, in women with breast cancer who received neoadjuvant chemotherapy.
Abstract: There is a need to improve prediction of response to chemotherapy in breast cancer in order to improve clinical management and this may be achieved by harnessing computational metrics of tissue pathology. We investigated the association between quantitative image metrics derived from computational analysis of digital pathology slides and response to chemotherapy in women with breast cancer who received neoadjuvant chemotherapy. We digitised tissue sections of both diagnostic and surgical samples of breast tumours from 768 patients enrolled in the Neo-tAnGo randomized controlled trial. We subjected digital images to systematic analysis optimised for detection of single cells. Machine-learning methods were used to classify cells as cancer, stromal or lymphocyte and we computed estimates of absolute numbers, relative fractions and cell densities using these data. Pathological complete response (pCR), a histological indicator of chemotherapy response, was the primary endpoint. Fifteen image metrics were tested for their association with pCR using univariate and multivariate logistic regression. Median lymphocyte density proved most strongly associated with pCR on univariate analysis (OR 4.46, 95 % CI 2.34-8.50, p < 0.0001; observations = 614) and on multivariate analysis (OR 2.42, 95 % CI 1.08-5.40, p = 0.03; observations = 406) after adjustment for clinical factors. Further exploratory analyses revealed that in approximately one quarter of cases there was an increase in lymphocyte density in the tumour removed at surgery compared to diagnostic biopsies. A reduction in lymphocyte density at surgery was strongly associated with pCR (OR 0.28, 95 % CI 0.17-0.47, p < 0.0001; observations = 553). A data-driven analysis of computational pathology reveals lymphocyte density as an independent predictor of pCR. Paradoxically an increase in lymphocyte density, following exposure to chemotherapy, is associated with a lack of pCR. Computational pathology can provide objective, quantitative and reproducible tissue metrics and represents a viable means of outcome prediction in breast cancer. ClinicalTrials.gov NCT00070278 ; 03/10/2003

62 citations

Journal ArticleDOI
TL;DR: In this article, the Initial Star formation and Lifetimes of Andromeda Satellites (ISLAndS) project employed Hubble Space Telescope imaging to study a representative sample of six Andromeda dSph satellite companion galaxies.
Abstract: The Initial Star formation and Lifetimes of Andromeda Satellites (ISLAndS) project employs Hubble Space Telescope imaging to study a representative sample of six Andromeda dSph satellite companion galaxies. Our main goal is to determine whether the star formation histories (SFHs) of the Andromeda dSph satellites demonstrate significant statistical differences from those of the Milky Way (MW). Our deep observations yield a time resolution at the oldest ages of ∼1 Gyr, allowing meaningful comparisons to the MW satellites. The six dSphs present a variety of SFHs (e.g., a significant range in quenching times, τq, from 9 to 6 Gyr ago) that are not strictly correlated with luminosity or present distance from M31. In agreement with observations of MW companions of similar mass, there is no evidence of complete quenching of star formation by the cosmic UV background responsible for reionization, but the possibility of a degree of quenching at reionization cannot be ruled out. We do not find significant differences between the SFHs of the members and non-members of the vast, thin plane of satellites. The SFHs of the ISLAndS M31 dSphs appear to be more uniform than those of the MW dSphs. Specifically, the primary difference between the SFHs of the ISLAndS dSphs and MW dSph companions of similar luminosities and host distances is the absence of late-quenching (τq ⩽ 5 Gyr) dSphs in the ISLAndS sample. Thus, models that can produce satellite populations with and without late-quenching satellites are of extreme interest.

62 citations

Journal ArticleDOI
TL;DR: In this paper, the authors used He-burning red clump stars as tracers for the analysis of the Canis Major system in the Galactic plane and found that the main body of the system has an integrated absolute magnitude M V = -14.4 ± 0.8, a central surface brightness μ V,0 ≃ 24.0 ± 1.6 and a line-of-sight (LOS) profile peaked at D ⊙ = 7.0 kpc with half width at half maximum ∼ 2.
Abstract: The recently discovered stellar system in Canis Major is analysed using He-burning red clump stars as tracers. Canis Major turns out to be the strongest and the most spatially confined overdensity of the whole Galactic disc, in terms of both number density and statistical significance. When projected on to the Galactic plane, it appears as an elongated and compact overdensity extending from l ∼ 200° to 280° with a roundish core towards l ∼240°. We find that the main body of the system has an integrated absolute magnitude M V = -14.4 ± 0.8, a central surface brightness μ V,0 ≃ 24.0 ± 0.6 and a line-of-sight (LOS) profile peaked at D ⊙ = 7.2 ± 1.0 kpc with half width at half maximum ∼ 2.0kpc, in excellent agreement with the results obtained with widely different tracers (M giants and main-sequence stars) in previous analyses. The mean distance to the main body of Canis Major is observed to increase with increasing Galactic longitude, from D ⊙ ≃ 6.3 kpc at l ≃ 225° to D ⊙ ≃ 9.3 kpc at l ≃ 265°, in good agreement with the predictions of our more recent N-body simulation that models Canis Major (CMa) as a dwarf galaxy being accreted in a planar orbit on to the disc of the Milky Way. We confirm that the Canis Major system has all the characteristics of the relic of a dwarf galaxy seen on top of a large-scale overdensity that we detect all over the third and fourth Galactic quadrants (180° ≤ l ≤ 360°, with a strong maximum around l = 290° and b ≥ -5°) that is identified as the stellar component of the Southern Galactic warp. On the other hand, the possibility that a peculiar deformation/asymmetry of the outer Galactic disc may be at the origin of the observed distribution of overdensities towards CMa cannot be definitely ruled out with the data presented in this paper. We also address a recent claim that Canis Major is on the outskirts of a larger 'Argo' structure centred at l ≃ 290°. Our analysis shows that the stellar populations in the latter are distributed over a very large distance range along the LOS, and do not give rise to a narrow peak in density in this direction, contrary to what is observed in Canis Major. This suggests that the Argo structure is likely due to Galactic asymmetries such as the warn.

62 citations

Journal ArticleDOI
TL;DR: In this article, the authors report on the Galactic stellar structures that appear in the foreground of the Canada-France-Hawaii-Telecopse/MegaCam survey of the halo of the Andromeda galaxy and recover the main sequence and main sequence turnoff of the Triangulum-Andromeda structure recently found by Majewski and collaborators at a heliocentric distance of ~20 kpc.
Abstract: This letter reports on the Galactic stellar structures that appear in the foreground of our Canada-France-Hawaii-Telecopse/MegaCam survey of the halo of the Andromeda galaxy. We recover the main sequence and main sequence turn-off of the Triangulum-Andromeda structure recently found by Majewski and collaborators at a heliocentric distance of ~20 kpc. The survey also reveals another less populated main sequence at fainter magnitudes that could correspond to a more distant stellar structure at ~28 kpc. Both structures are smoothly distributed over the ~76 sq. deg. covered by the survey although the closer one shows an increase in density by a factor of ~2 towards the North-West. The discovery of a stellar structure behind the Triangulum-Andromeda structure that itself appears behind the low-latitude stream that surrounds the Galactic disk gives further evidence that the inner halo of the Milky Way is of a spatially clumpy nature.

62 citations

Journal ArticleDOI
TL;DR: In this paper, the stellar structure of the isolated, Local Group dwarf galaxy Pegasus (DDO 216) was compared with low-resolution H I maps from L. M. Young et al. They concluded that this is strong evidence for an intergalactic medium associated with the Local Group.
Abstract: We compare the stellar structure of the isolated, Local Group dwarf galaxy Pegasus (DDO 216) with low-resolution H I maps from L. M. Young et al. Our comparison reveals that Pegasus displays the characteristic morphology of ram pressure stripping; in particular, the H I has a "cometary" appearance that is not reflected in the regular, elliptical distribution of the stars. This is the first time this phenomenon has been observed in an isolated Local Group galaxy. The density of the medium required to ram pressure strip Pegasus is at least 10-5 to 10-6 cm-3. We conclude that this is strong evidence for an intergalactic medium associated with the Local Group.

61 citations


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TL;DR: In this paper, the mass density, Omega_M, and cosmological-constant energy density of the universe were measured using the analysis of 42 Type Ia supernovae discovered by the Supernova Cosmology project.
Abstract: We report measurements of the mass density, Omega_M, and cosmological-constant energy density, Omega_Lambda, of the universe based on the analysis of 42 Type Ia supernovae discovered by the Supernova Cosmology Project. The magnitude-redshift data for these SNe, at redshifts between 0.18 and 0.83, are fit jointly with a set of SNe from the Calan/Tololo Supernova Survey, at redshifts below 0.1, to yield values for the cosmological parameters. All SN peak magnitudes are standardized using a SN Ia lightcurve width-luminosity relation. The measurement yields a joint probability distribution of the cosmological parameters that is approximated by the relation 0.8 Omega_M - 0.6 Omega_Lambda ~= -0.2 +/- 0.1 in the region of interest (Omega_M <~ 1.5). For a flat (Omega_M + Omega_Lambda = 1) cosmology we find Omega_M = 0.28{+0.09,-0.08} (1 sigma statistical) {+0.05,-0.04} (identified systematics). The data are strongly inconsistent with a Lambda = 0 flat cosmology, the simplest inflationary universe model. An open, Lambda = 0 cosmology also does not fit the data well: the data indicate that the cosmological constant is non-zero and positive, with a confidence of P(Lambda > 0) = 99%, including the identified systematic uncertainties. The best-fit age of the universe relative to the Hubble time is t_0 = 14.9{+1.4,-1.1} (0.63/h) Gyr for a flat cosmology. The size of our sample allows us to perform a variety of statistical tests to check for possible systematic errors and biases. We find no significant differences in either the host reddening distribution or Malmquist bias between the low-redshift Calan/Tololo sample and our high-redshift sample. The conclusions are robust whether or not a width-luminosity relation is used to standardize the SN peak magnitudes.

16,838 citations

Journal ArticleDOI
TL;DR: In this article, the authors used spectral and photometric observations of 10 Type Ia supernovae (SNe Ia) in the redshift range 0.16 " z " 0.62.
Abstract: We present spectral and photometric observations of 10 Type Ia supernovae (SNe Ia) in the redshift range 0.16 " z " 0.62. The luminosity distances of these objects are determined by methods that employ relations between SN Ia luminosity and light curve shape. Combined with previous data from our High-z Supernova Search Team and recent results by Riess et al., this expanded set of 16 high-redshift supernovae and a set of 34 nearby supernovae are used to place constraints on the following cosmo- logical parameters: the Hubble constant the mass density the cosmological constant (i.e., the (H 0 ), () M ), vacuum energy density, the deceleration parameter and the dynamical age of the universe ) " ), (q 0 ), ) M \ 1) methods. We estimate the dynamical age of the universe to be 14.2 ^ 1.7 Gyr including systematic uncer- tainties in the current Cepheid distance scale. We estimate the likely e†ect of several sources of system- atic error, including progenitor and metallicity evolution, extinction, sample selection bias, local perturbations in the expansion rate, gravitational lensing, and sample contamination. Presently, none of these e†ects appear to reconcile the data with and ) " \ 0 q 0 " 0.

16,674 citations

Journal ArticleDOI
22 Dec 2000-Science
TL;DR: An approach to solving dimensionality reduction problems that uses easily measured local metric information to learn the underlying global geometry of a data set and efficiently computes a globally optimal solution, and is guaranteed to converge asymptotically to the true structure.
Abstract: Scientists working with large volumes of high-dimensional data, such as global climate patterns, stellar spectra, or human gene distributions, regularly confront the problem of dimensionality reduction: finding meaningful low-dimensional structures hidden in their high-dimensional observations. The human brain confronts the same problem in everyday perception, extracting from its high-dimensional sensory inputs-30,000 auditory nerve fibers or 10(6) optic nerve fibers-a manageably small number of perceptually relevant features. Here we describe an approach to solving dimensionality reduction problems that uses easily measured local metric information to learn the underlying global geometry of a data set. Unlike classical techniques such as principal component analysis (PCA) and multidimensional scaling (MDS), our approach is capable of discovering the nonlinear degrees of freedom that underlie complex natural observations, such as human handwriting or images of a face under different viewing conditions. In contrast to previous algorithms for nonlinear dimensionality reduction, ours efficiently computes a globally optimal solution, and, for an important class of data manifolds, is guaranteed to converge asymptotically to the true structure.

13,652 citations

Journal ArticleDOI
TL;DR: In this article, a combination of seven-year data from WMAP and improved astrophysical data rigorously tests the standard cosmological model and places new constraints on its basic parameters and extensions.
Abstract: The combination of seven-year data from WMAP and improved astrophysical data rigorously tests the standard cosmological model and places new constraints on its basic parameters and extensions. By combining the WMAP data with the latest distance measurements from the baryon acoustic oscillations (BAO) in the distribution of galaxies and the Hubble constant (H0) measurement, we determine the parameters of the simplest six-parameter ΛCDM model. The power-law index of the primordial power spectrum is ns = 0.968 ± 0.012 (68% CL) for this data combination, a measurement that excludes the Harrison–Zel’dovich–Peebles spectrum by 99.5% CL. The other parameters, including those beyond the minimal set, are also consistent with, and improved from, the five-year results. We find no convincing deviations from the minimal model. The seven-year temperature power spectrum gives a better determination of the third acoustic peak, which results in a better determination of the redshift of the matter-radiation equality epoch. Notable examples of improved parameters are the total mass of neutrinos, � mν < 0.58 eV (95% CL), and the effective number of neutrino species, Neff = 4.34 +0.86 −0.88 (68% CL), which benefit from better determinations of the third peak and H0. The limit on a constant dark energy equation of state parameter from WMAP+BAO+H0, without high-redshift Type Ia supernovae, is w =− 1.10 ± 0.14 (68% CL). We detect the effect of primordial helium on the temperature power spectrum and provide a new test of big bang nucleosynthesis by measuring Yp = 0.326 ± 0.075 (68% CL). We detect, and show on the map for the first time, the tangential and radial polarization patterns around hot and cold spots of temperature fluctuations, an important test of physical processes at z = 1090 and the dominance of adiabatic scalar fluctuations. The seven-year polarization data have significantly improved: we now detect the temperature–E-mode polarization cross power spectrum at 21σ , compared with 13σ from the five-year data. With the seven-year temperature–B-mode cross power spectrum, the limit on a rotation of the polarization plane due to potential parity-violating effects has improved by 38% to Δα =− 1. 1 ± 1. 4(statistical) ± 1. 5(systematic) (68% CL). We report significant detections of the Sunyaev–Zel’dovich (SZ) effect at the locations of known clusters of galaxies. The measured SZ signal agrees well with the expected signal from the X-ray data on a cluster-by-cluster basis. However, it is a factor of 0.5–0.7 times the predictions from “universal profile” of Arnaud et al., analytical models, and hydrodynamical simulations. We find, for the first time in the SZ effect, a significant difference between the cooling-flow and non-cooling-flow clusters (or relaxed and non-relaxed clusters), which can explain some of the discrepancy. This lower amplitude is consistent with the lower-than-theoretically expected SZ power spectrum recently measured by the South Pole Telescope Collaboration.

11,309 citations

Journal ArticleDOI
Peter A. R. Ade1, Nabila Aghanim2, Monique Arnaud3, M. Ashdown4  +334 moreInstitutions (82)
TL;DR: In this article, the authors present a cosmological analysis based on full-mission Planck observations of temperature and polarization anisotropies of the cosmic microwave background (CMB) radiation.
Abstract: This paper presents cosmological results based on full-mission Planck observations of temperature and polarization anisotropies of the cosmic microwave background (CMB) radiation. Our results are in very good agreement with the 2013 analysis of the Planck nominal-mission temperature data, but with increased precision. The temperature and polarization power spectra are consistent with the standard spatially-flat 6-parameter ΛCDM cosmology with a power-law spectrum of adiabatic scalar perturbations (denoted “base ΛCDM” in this paper). From the Planck temperature data combined with Planck lensing, for this cosmology we find a Hubble constant, H0 = (67.8 ± 0.9) km s-1Mpc-1, a matter density parameter Ωm = 0.308 ± 0.012, and a tilted scalar spectral index with ns = 0.968 ± 0.006, consistent with the 2013 analysis. Note that in this abstract we quote 68% confidence limits on measured parameters and 95% upper limits on other parameters. We present the first results of polarization measurements with the Low Frequency Instrument at large angular scales. Combined with the Planck temperature and lensing data, these measurements give a reionization optical depth of τ = 0.066 ± 0.016, corresponding to a reionization redshift of . These results are consistent with those from WMAP polarization measurements cleaned for dust emission using 353-GHz polarization maps from the High Frequency Instrument. We find no evidence for any departure from base ΛCDM in the neutrino sector of the theory; for example, combining Planck observations with other astrophysical data we find Neff = 3.15 ± 0.23 for the effective number of relativistic degrees of freedom, consistent with the value Neff = 3.046 of the Standard Model of particle physics. The sum of neutrino masses is constrained to ∑ mν < 0.23 eV. The spatial curvature of our Universe is found to be very close to zero, with | ΩK | < 0.005. Adding a tensor component as a single-parameter extension to base ΛCDM we find an upper limit on the tensor-to-scalar ratio of r0.002< 0.11, consistent with the Planck 2013 results and consistent with the B-mode polarization constraints from a joint analysis of BICEP2, Keck Array, and Planck (BKP) data. Adding the BKP B-mode data to our analysis leads to a tighter constraint of r0.002 < 0.09 and disfavours inflationarymodels with a V(φ) ∝ φ2 potential. The addition of Planck polarization data leads to strong constraints on deviations from a purely adiabatic spectrum of fluctuations. We find no evidence for any contribution from isocurvature perturbations or from cosmic defects. Combining Planck data with other astrophysical data, including Type Ia supernovae, the equation of state of dark energy is constrained to w = −1.006 ± 0.045, consistent with the expected value for a cosmological constant. The standard big bang nucleosynthesis predictions for the helium and deuterium abundances for the best-fit Planck base ΛCDM cosmology are in excellent agreement with observations. We also constraints on annihilating dark matter and on possible deviations from the standard recombination history. In neither case do we find no evidence for new physics. The Planck results for base ΛCDM are in good agreement with baryon acoustic oscillation data and with the JLA sample of Type Ia supernovae. However, as in the 2013 analysis, the amplitude of the fluctuation spectrum is found to be higher than inferred from some analyses of rich cluster counts and weak gravitational lensing. We show that these tensions cannot easily be resolved with simple modifications of the base ΛCDM cosmology. Apart from these tensions, the base ΛCDM cosmology provides an excellent description of the Planck CMB observations and many other astrophysical data sets.

10,728 citations