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