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Exploring Meaningful Patient Engagement in ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness).
BackgroundGenuine patient engagement can improve research relevance, impact and is required for studies using the National Patient-Centered Clinical Research Network including major multicenter research projects. It is unclear, however, how best to integrate patients into governance of such projects.MethodsADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness) is the first major multicenter research project to be conducted in National Patient-Centered Clinical Research Network. Here, we provide a description of how we implemented patient engagement in ADAPTABLE thus far, including a description of committee structures and composition, first-hand patient testimonials, specific contributions, and lessons learned during the planning and early implementation of ADAPTABLE.ResultsWe recruited 1 patient leader from 6 of the 7 enrolling networks to serve on a Patient Review Board for ADAPTABLE, supported the Board with an experienced patient engagement team including an "investigator-advocate" not otherwise involved in the trial, and facilitated bidirectional communication between the Board and ADAPTABLE Coordinating Center. The Board has reviewed and provided substantial input on the informed consent procedure, recruitment materials, patient portal design, and study policy including compensation of participants. Although it was "too late" for some suggested modifications, most modifications suggested by the patient leaders have been implemented, and they are enthusiastic about the study and their role. The patient leaders also attend Steering and Executive Committee calls; these experiences have been somewhat less productive.ConclusionsWith adequate support, a cadre of committed patient leaders can provide substantial value to design and implementation of a major multicenter clinical trial
The Regulation of Pulmonary Immunity
This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.No evidence has emerged which suggests that the principles of immunity derived from studies on cells from other body sites are contradicted in the lung and its associated lymphoid tissue. What is clear, however, is that the environment dictates the types of cells, their relationship to one another, and what perturbing events will set in motion either the development of an "active" immune response or tolerance. Investigating mechanisms for the development of lung immunity has increased our understanding of how human diseases develop and is continuing to suggest new ways to manipulate pulmonary immune responses. Demonstration that lung cells regulate both nonspecific inflammation and immunity through the expression of adhesion molecules and the secretion of cytokines offers hope for ways to design more effective vaccines, enhance microbial clearance in immunosuppressed hosts, and to suppress manifestations of immunologically mediated lung disease. Important lung diseases targeted for intensive research efforts in the immediate future are tuberculosis, asthma, and fibrotic lung disease. Perhaps even the common cold might be conquered. Considering the pace of current research on lung immunity, it may not be too ambitious to predict that these diseases may be conquered in the next decade
Bringing "The Moth" to Light: A Planet-Sculpting Scenario for the HD 61005 Debris Disk
The HD 61005 debris disk ("The Moth") stands out from the growing collection
of spatially resolved circumstellar disks by virtue of its unusual swept-back
morphology, brightness asymmetries, and dust ring offset. Despite several
suggestions for the physical mechanisms creating these features, no definitive
answer has been found. In this work, we demonstrate the plausibility of a
scenario in which the disk material is shaped dynamically by an eccentric,
inclined planet. We present new Keck NIRC2 scattered-light angular differential
imaging of the disk at 1.2-2.3 microns that further constrains its outer
morphology (projected separations of 27-135 AU). We also present complementary
Gemini Planet Imager 1.6 micron total intensity and polarized light detections
that probe down to projected separations less than 10 AU. To test our
planet-sculpting hypothesis, we employed secular perturbation theory to
construct parent body and dust distributions that informed scattered-light
models. We found that this method produced models with morphological and
photometric features similar to those seen in the data, supporting the premise
of a planet-perturbed disk. Briefly, our results indicate a disk parent body
population with a semimajor axis of 40-52 AU and an interior planet with an
eccentricity of at least 0.2. Many permutations of planet mass and semimajor
axis are allowed, ranging from an Earth mass at 35 AU to a Jupiter mass at 5
AU.Comment: Accepted to AJ; added Figure 5 and minor text edit
Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases
In women, breast cancer is the most common cancer diagnosis and second most common cause of cancer death. More than half of breast cancer patients will develop metastases to the bone, liver, lung, or brain. Breast cancer brain metastases (BCBM) confers a poor prognosis, as current therapeutic options of surgery, radiation, and chemotherapy rarely significantly extend life and are considered palliative. Within the realm of chemotherapy, the last decade has seen an explosion of novel chemotherapeutics involving targeting agents and unique dosage forms. We provide a historical overview of BCBM chemotherapy, review the mechanisms of new agents such as poly-ADP ribose polymerase inhibitors, cyclin-dependent kinase 4/6 inhibitors, phosphatidyl inositol 3-kinaseinhibitors, estrogen pathway antagonists for hormone-receptor positive BCBM; tyrosine kinase inhibitors, antibodies, and conjugates for HER2+ BCBM; repurposed cytotoxic chemotherapy for triple negative BCBM; and the utilization of these new agents and formulations in ongoing clinical trials. The mechanisms of novel dosage formulations such as nanoparticles, liposomes, pegylation, the concepts of enhanced permeation and retention, and drugs utilizing these concepts involved in clinical trials are also discussed. These new treatments provide a promising outlook in the treatment of BCBM
Type II Supernovae as Probes of Cosmology
- Constraining the cosmological parameters and understanding Dark Energy have
tremendous implications for the nature of the Universe and its physical laws.
- The pervasive limit of systematic uncertainties reached by cosmography
based on Cepheids and Type Ia supernovae (SNe Ia) warrants a search for
complementary approaches.
- Type II SNe have been shown to offer such a path. Their distances can be
well constrained by luminosity-based or geometric methods. Competing,
complementary, and concerted efforts are underway, to explore and exploit those
objects that are extremely well matched to next generation facilities.
Spectroscopic follow-up will be enabled by space- based and 20-40 meter class
telescopes.
- Some systematic uncertainties of Type II SNe, such as reddening by dust and
metallicity effects, are bound to be different from those of SNe Ia. Their
stellar progenitors are known, promising better leverage on cosmic evolution.
In addition, their rate - which closely tracks the ongoing star formation rate
- is expected to rise significantly with look- back time, ensuring an adequate
supply of distant examples.
- These data will competitively constrain the dark energy equation of state,
allow the determination of the Hubble constant to 5%, and promote our
understanding of the processes involved in the last dramatic phases of massive
stellar evolution.Comment: Science white paper, submitted to the Decadal committee Astro201
Automated data processing architecture for the Gemini Planet Imager Exoplanet Survey
The Gemini Planet Imager Exoplanet Survey (GPIES) is a multi-year direct
imaging survey of 600 stars to discover and characterize young Jovian
exoplanets and their environments. We have developed an automated data
architecture to process and index all data related to the survey uniformly. An
automated and flexible data processing framework, which we term the Data
Cruncher, combines multiple data reduction pipelines together to process all
spectroscopic, polarimetric, and calibration data taken with GPIES. With no
human intervention, fully reduced and calibrated data products are available
less than an hour after the data are taken to expedite follow-up on potential
objects of interest. The Data Cruncher can run on a supercomputer to reprocess
all GPIES data in a single day as improvements are made to our data reduction
pipelines. A backend MySQL database indexes all files, which are synced to the
cloud, and a front-end web server allows for easy browsing of all files
associated with GPIES. To help observers, quicklook displays show reduced data
as they are processed in real-time, and chatbots on Slack post observing
information as well as reduced data products. Together, the GPIES automated
data processing architecture reduces our workload, provides real-time data
reduction, optimizes our observing strategy, and maintains a homogeneously
reduced dataset to study planet occurrence and instrument performance.Comment: 21 pages, 3 figures, accepted in JATI
OpenFermion: The Electronic Structure Package for Quantum Computers
Quantum simulation of chemistry and materials is predicted to be an important
application for both near-term and fault-tolerant quantum devices. However, at
present, developing and studying algorithms for these problems can be difficult
due to the prohibitive amount of domain knowledge required in both the area of
chemistry and quantum algorithms. To help bridge this gap and open the field to
more researchers, we have developed the OpenFermion software package
(www.openfermion.org). OpenFermion is an open-source software library written
largely in Python under an Apache 2.0 license, aimed at enabling the simulation
of fermionic models and quantum chemistry problems on quantum hardware.
Beginning with an interface to common electronic structure packages, it
simplifies the translation between a molecular specification and a quantum
circuit for solving or studying the electronic structure problem on a quantum
computer, minimizing the amount of domain expertise required to enter the
field. The package is designed to be extensible and robust, maintaining high
software standards in documentation and testing. This release paper outlines
the key motivations behind design choices in OpenFermion and discusses some
basic OpenFermion functionality which we believe will aid the community in the
development of better quantum algorithms and tools for this exciting area of
research.Comment: 22 page
Constraints on the architecture of the HD 95086 planetary system with the Gemini Planet Imager
We present astrometric monitoring of the young exoplanet HD 95086 b obtained
with the Gemini Planet Imager between 2013 and 2016. A small but significant
position angle change is detected at constant separation; the orbital motion is
confirmed with literature measurements. Efficient Monte Carlo techniques place
preliminary constraints on the orbital parameters of HD 95086 b. With 68%
confidence, a semimajor axis of 61.7^{+20.7}_{-8.4} au and an inclination of
153.0^{+9.7}_{-13.5} deg are favored, with eccentricity less than 0.21. Under
the assumption of a co-planar planet-disk system, the periastron of HD 95086 b
is beyond 51 au with 68% confidence. Therefore HD 95086 b cannot carve the
entire gap inferred from the measured infrared excess in the SED of HD 95086.
We use our sensitivity to additional planets to discuss specific scenarios
presented in the literature to explain the geometry of the debris belts. We
suggest that either two planets on moderately eccentric orbits or three to four
planets with inhomogeneous masses and orbital properties are possible. The
sensitivity to additional planetary companions within the observations
presented in this study can be used to help further constrain future dynamical
simulations of the planet-disk system.Comment: Accepted for publication in ApJ
Dynamical Mass Measurement of the Young Spectroscopic Binary V343 Normae AaAb Resolved With the Gemini Planet Imager
We present new spatially resolved astrometry and photometry from the Gemini
Planet Imager of the inner binary of the young multiple star system V343
Normae, which is a member of the beta Pictoris moving group. V343 Normae
comprises a K0 and mid-M star in a ~4.5 year orbit (AaAb) and a wide 10" M5
companion (B). By combining these data with archival astrometry and radial
velocities we fit the orbit and measure individual masses for both components
of M_Aa = 1.10 +/- 0.10 M_sun and M_Ab = 0.290 +/- 0.018 M_sun. Comparing to
theoretical isochrones, we find good agreement for the measured masses and JHK
band magnitudes of the two components consistent with the age of the beta Pic
moving group. We derive a model-dependent age for the beta Pic moving group of
26 +/- 3 Myr by combining our results for V343 Normae with literature
measurements for GJ 3305, which is another group member with resolved binary
components and dynamical masses.Comment: 12 pages, 7 figures. Accepted to A
Type Ia Supernova Rate Measurements To Redshift 2.5 From CANDELS: Searching For Prompt Explosions In The Early Universe
dThe Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) was a multi-cycle treasury program on the Hubble Space Telescope (HST) that surveyed a total area of -0.25 deg2 with -900 HST orbits spread across five fields over three years. Within these survey images we discovered 65 supernovae (SNe) of all types, out to z 2.5. We classify -24 of these as Type Ia SNe (SNe Ia) based on host galaxy redshifts and SN photometry (supplemented by grism spectroscopy of six SNe). Here we present a measurement of the volumetric SN Ia rate as a function of redshift, reaching for the first time beyond z =- 2 and putting new constraints on SN Ia progenitor models. Our highest redshift bin includes detections of SNe that exploded when the universe was only -3 Gyr old and near the peak of the cosmic star formation history. This gives the CANDELS high redshift sample unique leverage for evaluating the fraction of SNe Ia that explode promptly after formation ( 40 Myr. However, mild tension is apparent between ground-based low-z surveys and space-based high-z surveys. In both CANDELS and the sister HST program CLASH (Cluster Lensing And Supernova Survey with Hubble), we find a low rate of SNe Ia at z > 1. This could be a hint that prompt progenitors are in fact relatively rare, accounting for only 20% of all SN Ia explosions-though further analysis and larger samples will be needed to examine that suggestion. Key words: infrared: general - supernovae:Astronom
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