419 research outputs found
Management of diarrhea in patients with HER2-positive breast cancer treated with neratinib: A case series and summary of the literature
INTRODUCTION: Neratinib and neratinib-based combinations have demonstrated efficacy for treatment of human epidermal growth factor receptor 2-positive (HER2+) early-stage and metastatic breast cancers. However, diarrhea has been reported as a common adverse event leading to neratinib discontinuation. Results from the CONTROL trial suggest that proactive diarrhea management with antidiarrheal prophylaxis or dose escalation of neratinib from a lower starting dose to the full FDA-approved dose of 240 mg/day can reduce the incidence, duration, and severity of neratinib-associated diarrhea in patients with early-stage breast cancer. Dose escalation has been included in the FDA-approved label for both early-stage and metastatic HER2+ breast cancer since June 2021.
CASE SERIES: This series of five cases details real-world clinical implementation of strategies for management of neratinib-induced diarrhea in patients with early-stage and metastatic HER2+ breast cancer, including a patient with a pre-existing gastrointestinal disorder.
MANAGEMENT AND OUTCOME: In four of five cases, diarrhea was managed with neratinib dose escalation, and antidiarrheal prophylaxis with loperamide plus colestipol was used in the remaining case. Management of diarrhea allowed all patients to remain on therapy.
DISCUSSION: This case series shows that neratinib-associated diarrhea can be managed effectively with neratinib dose escalation from a lower initial starting dose and/or prophylactic antidiarrheal medications in a real-world clinical setting. The findings highlight the importance of patient-provider communication in proactive management of adverse events. Widespread implementation of the strategies described here may improve adherence and thereby clinical outcomes for patients with HER2+ breast cancer treated with neratinib
Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog with Measured Completeness and Reliability Based on Data Release 25
We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching 4 yr of Kepler time series photometry (Data Release 25, Q1–Q17). The catalog contains 8054 KOIs, of which 4034 are planet candidates with periods between 0.25 and 632 days. Of these candidates, 219 are new, including two in multiplanet systems (KOI-82.06 and KOI-2926.05) and 10 high-reliability, terrestrial-size, habitable zone candidates. This catalog was created using a tool called the Robovetter, which automatically vets the DR25 threshold crossing events (TCEs). The Robovetter also vetted simulated data sets and measured how well it was able to separate TCEs caused by noise from those caused by low signal-to-noise transits. We discuss the Robovetter and the metrics it uses to sort TCEs. For orbital periods less than 100 days the Robovetter completeness (the fraction of simulated transits that are determined to be planet candidates) across all observed stars is greater than 85%. For the same period range, the catalog reliability (the fraction of candidates that are not due to instrumental or stellar noise) is greater than 98%. However, for low signal-to-noise candidates between 200 and 500 days around FGK-dwarf stars, the Robovetter is 76.7% complete and the catalog is 50.5% reliable. The KOI catalog, the transit fits, and all of the simulated data used to characterize this catalog are available at the NASA Exoplanet Archive
Discovery and Rossiter-McLaughlin Effect of Exoplanet Kepler-8b
We report the discovery and the Rossiter-McLaughlin effect of Kepler-8b, a
transiting planet identified by the NASA Kepler Mission. Kepler photometry and
Keck-HIRES radial velocities yield the radius and mass of the planet around
this F8IV subgiant host star. The planet has a radius RP = 1.419 RJ and a mass,
MP = 0.60 MJ, yielding a density of 0.26 g cm^-3, among the lowest density
planets known. The orbital period is P = 3.523 days and orbital semima jor axis
is 0.0483+0.0006/-0.0012 AU. The star has a large rotational v sin i of 10.5
+/- 0.7 km s^-1 and is relatively faint (V = 13.89 mag), both properties
deleterious to precise Doppler measurements. The velocities are indeed noisy,
with scatter of 30 m s^-1, but exhibit a period and phase consistent with the
planet implied by the photometry. We securely detect the Rossiter-McLaughlin
effect, confirming the planet's existence and establishing its orbit as
prograde. We measure an inclination between the projected planetary orbital
axis and the projected stellar rotation axis of lambda = -26.9 +/- 4.6 deg,
indicating a moderate inclination of the planetary orbit. Rossiter-McLaughlin
measurements of a large sample of transiting planets from Kepler will provide a
statistically robust measure of the true distribution of spin-orbit
orientations for hot jupiters in general.Comment: 26 pages, 8 figures, 2 tables; In preparation for submission to the
Astrophysical Journa
Planetary Candidates Observed by Kepler V: Planet Sample from Q1-Q12 (36 Months)
The Kepler mission discovered 2842 exoplanet candidates with 2 years of data.
We provide updates to the Kepler planet candidate sample based upon 3 years
(Q1-Q12) of data. Through a series of tests to exclude false-positives,
primarily caused by eclipsing binary stars and instrumental systematics, 855
additional planetary candidates have been discovered, bringing the total number
known to 3697. We provide revised transit parameters and accompanying posterior
distributions based on a Markov Chain Monte Carlo algorithm for the cumulative
catalogue of Kepler Objects of Interest. There are now 130 candidates in the
cumulative catalogue that receive less than twice the flux the Earth receives
and more than 1100 have a radius less than 1.5 Rearth. There are now a dozen
candidates meeting both criteria, roughly doubling the number of candidate
Earth analogs. A majority of planetary candidates have a high probability of
being bonafide planets, however, there are populations of likely
false-positives. We discuss and suggest additional cuts that can be easily
applied to the catalogue to produce a set of planetary candidates with good
fidelity. The full catalogue is publicly available at the NASA Exoplanet
Archive.Comment: Accepted for publication, ApJ
Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog With Measured Completeness and Reliability Based on Data Release 25
We present the Kepler Object of Interest (KOI) catalog of transiting
exoplanets based on searching four years of Kepler time series photometry (Data
Release 25, Q1-Q17). The catalog contains 8054 KOIs of which 4034 are planet
candidates with periods between 0.25 and 632 days. Of these candidates, 219 are
new and include two in multi-planet systems (KOI-82.06 and KOI-2926.05), and
ten high-reliability, terrestrial-size, habitable zone candidates. This catalog
was created using a tool called the Robovetter which automatically vets the
DR25 Threshold Crossing Events (TCEs, Twicken et al. 2016). The Robovetter also
vetted simulated data sets and measured how well it was able to separate TCEs
caused by noise from those caused by low signal-to-noise transits. We discusses
the Robovetter and the metrics it uses to sort TCEs. For orbital periods less
than 100 days the Robovetter completeness (the fraction of simulated transits
that are determined to be planet candidates) across all observed stars is
greater than 85%. For the same period range, the catalog reliability (the
fraction of candidates that are not due to instrumental or stellar noise) is
greater than 98%. However, for low signal-to-noise candidates between 200 and
500 days around FGK dwarf stars, the Robovetter is 76.7% complete and the
catalog is 50.5% reliable. The KOI catalog, the transit fits and all of the
simulated data used to characterize this catalog are available at the NASA
Exoplanet Archive.Comment: 61 pages, 23 Figures, 9 Tables, Accepted to The Astrophysical Journal
Supplement Serie
Transit Timing Observations from Kepler: III. Confirmation of 4 Multiple Planet Systems by a Fourier-Domain Study of Anti-correlated Transit Timing Variations
We present a method to confirm the planetary nature of objects in systems
with multiple transiting exoplanet candidates. This method involves a
Fourier-Domain analysis of the deviations in the transit times from a constant
period that result from dynamical interactions within the system. The
combination of observed anti-correlations in the transit times and mass
constraints from dynamical stability allow us to claim the discovery of four
planetary systems Kepler-25, Kepler-26, Kepler-27, and Kepler-28, containing
eight planets and one additional planet candidate.Comment: Accepted to MNRA
Planetary Candidates Observed by Kepler, III: Analysis of the First 16 Months of Data
New transiting planet candidates are identified in sixteen months (May 2009 -
September 2010) of data from the Kepler spacecraft. Nearly five thousand
periodic transit-like signals are vetted against astrophysical and instrumental
false positives yielding 1,091 viable new planet candidates, bringing the total
count up to over 2,300. Improved vetting metrics are employed, contributing to
higher catalog reliability. Most notable is the noise-weighted robust averaging
of multi-quarter photo-center offsets derived from difference image analysis
which identifies likely background eclipsing binaries. Twenty-two months of
photometry are used for the purpose of characterizing each of the new
candidates. Ephemerides (transit epoch, T_0, and orbital period, P) are
tabulated as well as the products of light curve modeling: reduced radius
(Rp/R*), reduced semi-major axis (d/R*), and impact parameter (b). The largest
fractional increases are seen for the smallest planet candidates (197% for
candidates smaller than 2Re compared to 52% for candidates larger than 2Re) and
those at longer orbital periods (123% for candidates outside of 50-day orbits
versus 85% for candidates inside of 50-day orbits). The gains are larger than
expected from increasing the observing window from thirteen months (Quarter 1--
Quarter 5) to sixteen months (Quarter 1 -- Quarter 6). This demonstrates the
benefit of continued development of pipeline analysis software. The fraction of
all host stars with multiple candidates has grown from 17% to 20%, and the
paucity of short-period giant planets in multiple systems is still evident. The
progression toward smaller planets at longer orbital periods with each new
catalog release suggests that Earth-size planets in the Habitable Zone are
forthcoming if, indeed, such planets are abundant.Comment: Submitted to ApJS. Machine-readable tables are available at
http://kepler.nasa.gov, http://archive.stsci.edu/kepler/results.html, and the
NASA Exoplanet Archiv
Planet Occurrence within 0.25 AU of Solar-type Stars from Kepler
We report the distribution of planets as a function of planet radius (R_p),
orbital period (P), and stellar effective temperature (Teff) for P < 50 day
orbits around GK stars. These results are based on the 1,235 planets (formally
"planet candidates") from the Kepler mission that include a nearly complete set
of detected planets as small as 2 Earth radii (Re). For each of the 156,000
target stars we assess the detectability of planets as a function of R_p and P.
We also correct for the geometric probability of transit, R*/a. We consider
first stars within the "solar subset" having Teff = 4100-6100 K, logg =
4.0-4.9, and Kepler magnitude Kp < 15 mag. We include only those stars having
noise low enough to permit detection of planets down to 2 Re. We count planets
in small domains of R_p and P and divide by the included target stars to
calculate planet occurrence in each domain. Occurrence of planets varies by
more than three orders of magnitude and increases substantially down to the
smallest radius (2 Re) and out to the longest orbital period (50 days, ~0.25
AU) in our study. For P < 50 days, the radius distribution is given by a power
law, df/dlogR= k R^\alpha. This rapid increase in planet occurrence with
decreasing planet size agrees with core-accretion, but disagrees with
population synthesis models. We fit occurrence as a function of P to a power
law model with an exponential cutoff below a critical period P_0. For smaller
planets, P_0 has larger values, suggesting that the "parking distance" for
migrating planets moves outward with decreasing planet size. We also measured
planet occurrence over Teff = 3600-7100 K, spanning M0 to F2 dwarfs. The
occurrence of 2-4 Re planets in the Kepler field increases with decreasing
Teff, making these small planets seven times more abundant around cool stars
than the hottest stars in our sample. [abridged]Comment: Submitted to ApJ, 22 pages, 10 figure
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Transiting circumbinary planets Kepler-34 b and Kepler-35 b
Most Sun-like stars in the Galaxy reside in gravitationally bound pairs of stars (binaries). Although long anticipated the existence of a ‘circumbinary planet’ orbiting such a pair of normal stars was not definitively established until the discovery of the planet transiting (that is, passing in front of) Kepler-16. Questions remained, however, about the prevalence of circumbinary planets and their range of orbital and physical properties. Here we report two additional transiting circumbinary planets: Kepler-34 (AB)b and Kepler-35 (AB)b, referred to here as Kepler-34 b and Kepler-35 b, respectively. Each is a low-density gas-giant planet on an orbit closely aligned with that of its parent stars. Kepler-34 b orbits two Sun-like stars every 289 days, whereas Kepler-35 b orbits a pair of smaller stars (89% and 81% of the Sun’s mass) every 131 days. The planets experience large multi-periodic variations in incident stellar radiation arising from the orbital motion of the stars. The observed rate of circumbinary planets in our sample implies that more than ~1% of close binary stars have giant planets in nearly coplanar orbits, yielding a Galactic population of at least several million
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