Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited.
We analysed clinical ...data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions.
Median age at diagnosis of BMs was 56 years (22–90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)–positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000–2009 with 2010–2015 (51%–44%), whereas the percentage of patients with luminal-like tumours increased (28%–34%; p = 0.0331). Patients with BMs in the posterior fossa were more often HER2 positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n = 65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p < 0.0001). Median overall survival (OS) time after development of BMs for the overall cohort was 7.4 months (95% confidence interval CI: 6.7–8.0 months). One-year survival rate was 37.7% (95% CI: 35.2–40.1). Patients with HER2-positive tumours had the longest median OS of 11.6 months (95% CI: 10.0–13.4) compared with 5.9 months (95% CI: 5.0–7.2) for patients with luminal-like and 4.6 months (95% CI: 3.9–5.4) for patients with triple-negative tumours. Patients with HER2-positive tumours who received anti-HER2 treatment had longer median OS than those without (17.1 months versus 7.2 months, p < 0.0001).
Prognosis of patients after developing BMs varies significantly according to the subtype. The outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2-negative patients. Our results underline the high medical need for improvement of treatment and prevention strategies for BMs in breast cancer patients.
•The first analysis of 1712 patients of breast cancer patients with brain metastases (BMs) is presented.•Localisation of BMs was different depending on tumour subtypes.•Survival times differ depending on the subtype and localisation of BMs.•A change in the incidence of BMs over time was observed.
ABSTRACT The Atacama Cosmology Telescope (ACT) makes high angular resolution measurements of anisotropies in the Cosmic Microwave Background (CMB) at millimeter wavelengths. We describe ACTPol, an ...upgraded receiver for ACT, which uses feedhorn-coupled, polarization-sensitive detector arrays, a 3° field of view, 100 mK cryogenics with continuous cooling, and meta material antireflection coatings. ACTPol comprises three arrays with separate cryogenic optics: two arrays at a central frequency of 148 GHz and one array operating simultaneously at both 97 GHz and 148 GHz. The combined instrument sensitivity, angular resolution, and sky coverage are optimized for measuring angular power spectra, clusters via the thermal Sunyaev-Zel'dovich (SZ) and kinetic SZ signals, and CMB lensing due to large-scale structure. The receiver was commissioned with its first 148 GHz array in 2013, observed with both 148 GHz arrays in 2014, and has recently completed its first full season of operations with the full suite of three arrays. This paper provides an overview of the design and initial performance of the receiver and related systems.
We report a study of ν(μ) charged-current quasielastic events in the segmented scintillator inner tracker of the MINERvA experiment running in the NuMI neutrino beam at Fermilab. The events were ...selected by requiring a μ- and low calorimetric recoil energy separated from the interaction vertex. We measure the flux-averaged differential cross section, dσ/dQ², and study the low energy particle content of the final state. Deviations are found between the measured dσ/dQ² and the expectations of a model of independent nucleons in a relativistic Fermi gas. We also observe an excess of energy near the vertex consistent with multiple protons in the final state.
Three masses of the Chelyabinsk meteorite have been studied with a wide range of analytical techniques to understand the mineralogical variation and thermal history of the Chelyabinsk parent body. ...The samples exhibit little to no postentry oxidation via Mössbauer and Raman spectroscopy indicating their fresh character, but despite the rapid collection and care of handling some low levels of terrestrial contamination did nonetheless result. Detailed studies show three distinct lithologies, indicative of a genomict breccia. A light‐colored lithology is LL5 material that has experienced thermal metamorphism and subsequent shock at levels near S4. The second lithology is a shock‐darkened LL5 material in which the darkening is caused by melt and metal‐troilite veins along grain boundaries. The third lithology is an impact melt breccia that formed at high temperatures (~1600 °C), and it experienced rapid cooling and degassing of S2 gas. Portions of light and dark lithologies from Chel‐101, and the impact melt breccias (Chel‐102 and Chel‐103) were prepared and analyzed for Rb‐Sr, Sm‐Nd, and Ar‐Ar dating. When combined with results from other studies and chronometers, at least eight impact events (e.g., ~4.53 Ga, ~4.45 Ga, ~3.73 Ga, ~2.81 Ga, ~1.46 Ga, ~852 Ma, ~312 Ma, and ~27 Ma) are clearly identified for Chelyabinsk, indicating a complex history of impacts and heating events. Finally, noble gases yield young cosmic ray exposure ages, near 1 Ma. These young ages, together with the absence of measurable cosmogenic derived Sm and Cr, indicate that Chelyabinsk may have been derived from a recent breakup event on an NEO of LL chondrite composition.
We have isolated ν(μ) charged-current quasielastic (QE) interactions occurring in the segmented scintillator tracking region of the MINERvA detector running in the NuMI neutrino beam at Fermilab. We ...measure the flux-averaged differential cross section, dσ/dQ², and compare to several theoretical models of QE scattering. Good agreement is obtained with a model where the nucleon axial mass, M(A), is set to 0.99 GeV/c² but the nucleon vector form factors are modified to account for the observed enhancement, relative to the free nucleon case, of the cross section for the exchange of transversely polarized photons in electron-nucleus scattering. Our data at higher Q² favor this interpretation over an alternative in which the axial mass is increased.
We search for an isotropic stochastic gravitational-wave background (GWB) in the newly released 11 year data set from the North American Nanohertz Observatory for Gravitational Waves (NANOGrav). ...While we find no evidence for a GWB, we place constraints on a population of inspiraling supermassive black hole (SMBH) binaries, a network of decaying cosmic strings, and a primordial GWB. For the first time, we find that the GWB constraints are sensitive to the solar system ephemeris (SSE) model used and that SSE errors can mimic a GWB signal. We developed an approach that bridges systematic SSE differences, producing the first pulsar-timing array (PTA) constraints that are robust against SSE errors. We thus place a 95% upper limit on the GW-strain amplitude of AGWB < 1.45 × 10−15 at a frequency of f = 1 yr−1 for a fiducial f−2/3 power-law spectrum and with interpulsar correlations modeled. This is a factor of ∼2 improvement over the NANOGrav nine-year limit calculated using the same procedure. Previous PTA upper limits on the GWB (as well as their astrophysical and cosmological interpretations) will need revision in light of SSE systematic errors. We use our constraints to characterize the combined influence on the GWB of the stellar mass density in galactic cores, the eccentricity of SMBH binaries, and SMBH-galactic-bulge scaling relationships. We constrain the cosmic-string tension using recent simulations, yielding an SSE-marginalized 95% upper limit of G < 5.3 × 10−11-a factor of ∼2 better than the published NANOGrav nine-year constraints. Our SSE-marginalized 95% upper limit on the energy density of a primordial GWB (for a radiation-dominated post-inflation universe) is GWB(f) h2 < 3.4 × 10−10.
The regularity of pulsar emissions becomes apparent once we reference the pulses' times of arrivals to the inertial rest frame of the solar system. It follows that errors in the determination of ...Earth's position with respect to the solar system barycenter can appear as a time-correlated bias in pulsar-timing residual time series, affecting the searches for low-frequency gravitational waves performed with pulsar-timing arrays. Indeed, recent array data sets yield different gravitational-wave background upper limits and detection statistics when analyzed with different solar system ephemerides. Crucially, the ephemerides do not generally provide usable error representations. In this article, we describe the motivation, construction, and application of a physical model of solar system ephemeris uncertainties, which focuses on the degrees of freedom (Jupiter's orbital elements) most relevant to gravitational-wave searches with pulsar-timing arrays. This model, BayesEphem, was used to derive ephemeris-robust results in NANOGrav's 11 yr stochastic-background search, and it provides a foundation for future searches by NANOGrav and other consortia. The analysis and simulations reported here suggest that ephemeris modeling reduces the gravitational-wave sensitivity of the 11 yr data set and that this degeneracy will vanish with improved ephemerides and with pulsar-timing data sets that extend well beyond a single Jovian orbital period.
Abstract
The DECam Local Volume Exploration survey (DELVE) is a 126-night survey program on the 4 m Blanco Telescope at the Cerro Tololo Inter-American Observatory in Chile. DELVE seeks to understand ...the characteristics of faint satellite galaxies and other resolved stellar substructures over a range of environments in the Local Volume. DELVE will combine new DECam observations with archival DECam data to cover ∼15,000 deg
2
of high Galactic latitude (∣
b
∣ > 10°) southern sky to a 5
σ
depth of
g
,
r
,
i
,
z
∼ 23.5 mag. In addition, DELVE will cover a region of ∼2200 deg
2
around the Magellanic Clouds to a depth of
g
,
r
,
i
∼ 24.5 mag and an area of ∼135 deg
2
around four Magellanic analogs to a depth of
g
,
i
∼ 25.5 mag. Here, we present an overview of the DELVE program and progress to date. We also summarize the first DELVE public data release (DELVE DR1), which provides point-source and automatic aperture photometry for ∼520 million astronomical sources covering ∼5000 deg
2
of the southern sky to a 5
σ
point-source depth of
g
= 24.3 mag,
r
= 23.9 mag,
i
= 23.3 mag, and
z
= 22.8 mag. DELVE DR1 is publicly available via the NOIRLab Astro Data Lab science platform.
Statistics of radio frequency interference (RFI) observed in the band 1398-1422 MHz during an airborne campaign in the United States are reported for use in analysis and forecasting of L-band RFI for ...microwave radiometry. The observations were conducted from September to October 2008, and included approximately 92 h of flight time, of which approximately 20 h of "transit" or dedicated RFI observing flights are used in compiling the statistics presented. The observations used include outbound and return flights from Colorado to Maryland, as well as RFI surveys over large cities. The Passive Active L-Band Sensor (PALS) radiometer of NASA Jet Propulsion Laboratory augmented by three dedicated RFI observing systems was used in these observations. The complete system as well as the associated RFI characterization approaches are described, along with the resulting RFI statistical information and examinations of specific RFI sources. The results show that RFI in the protected L-band spectrum is common over North America, although the resulting interference when extrapolated to satellite observations will appear as "low-level" corruption that will be difficult to detect for traditional radiometer systems.
A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS
) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of ...the PRS
with clinicopathologic characteristics of, and survival following, breast cancer.
Women with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS
and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS
(continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.
The PRS
was associated with more favorable tumor characteristics. In BCAC, increasing PRS
was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS
was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS
was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.
An increased PRS
is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS
has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS
as increasing PRS
is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.
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