Goal-Focused Emotion-Regulation Therapy (GET) for young adult survivors of testicular cancer: a pilot randomized controlled trial of a biobehavioral intervention protocol.

BackgroundTesticular cancer diagnosis and treatment, especially given its threat to sexuality and reproductive health, can be distressing in the formative period of young adulthood and the majority of young survivors experience impairing, distressing, and modifiable adverse outcomes that can persist long after medical treatment. These include psychological distress, impairment in pursuit of life goals, persistent physical side effects, elevated risk of secondary malignancies and chronic illness, and biobehavioral burden (e.g., enhanced inflammation, dysregulated diurnal stress hormones). However, few targeted interventions exist to assist young survivors in renegotiating life goals and regulating cancer-related emotions, and none focus on reducing the burden of morbidity via biobehavioral mechanisms. This paper describes the methodology of a randomized controlled biobehavioral trial designed to investigate the feasibility and preliminary impact of a novel intervention, Goal-focused Emotion-Regulation Therapy (GET), aimed at improving distress symptoms, emotion regulation, goal navigation skills, and stress-sensitive biomarkers in young adult testicular cancer patients.MethodsParticipants will be randomized to receive six sessions of GET or Individual Supportive Therapy (ISP) delivered over 8 weeks. In addition to indicators of intervention feasibility, we will measure primary (depressive and anxiety symptoms) and secondary (emotion regulation and goal navigation skills, career confusion) psychological outcomes prior to (T0), immediately after (T1), and 12 weeks after (T2) intervention. Additionally, identified biomarkers will be measured at baseline and at T2.DiscussionGET may have the potential to improve self-regulation across biobehavioral domains, improve overall cancer adjustment, and address the need for targeted supportive care interventions for young adult cancer survivors.Trial registrationClinicaltrials.gov, NCT04150848. Registered on 28 October 2019

The Solar Neighborhood. XXXIV. A Search for Planets Orbiting Nearby M Dwarfs using Astrometry

Astrometric measurements are presented for seven nearby stars with previously detected planets: six M dwarfs (GJ 317, GJ 667C, GJ 581, GJ 849, GJ 876, and GJ 1214) and one K dwarf (BD $-$10 3166). Measurements are also presented for six additional nearby M dwarfs without known planets, but which are more favorable to astrometric detections of low mass companions, as well as three binary systems for which we provide astrometric orbit solutions. Observations have baselines of three to thirteen years, and were made as part of the RECONS long-term astrometry and photometry program at the CTIO/SMARTS 0.9m telescope. We provide trigonometric parallaxes and proper motions for all 16 systems, and perform an extensive analysis of the astrometric residuals to determine the minimum detectable companion mass for the 12 M dwarfs not having close stellar secondaries. For the six M dwarfs with known planets, we are not sensitive to planets, but can rule out the presence of all but the least massive brown dwarfs at periods of 2 - 12 years. For the six more astrometrically favorable M dwarfs, we conclude that none have brown dwarf companions, and are sensitive to companions with masses as low as 1 $M_{Jup}$ for periods longer than two years. In particular, we conclude that Proxima Centauri has no Jovian companions at orbital periods of 2 - 12 years. These results complement previously published M dwarf planet occurrence rates by providing astrometrically determined upper mass limits on potential super-Jupiter companions at orbits of two years and longer. As part of a continuing survey, these results are consistent with the paucity of super-Jupiter and brown dwarf companions we find among the over 250 red dwarfs within 25 pc observed longer than five years in our astrometric program.Comment: 18 pages, 5 figures, 4 tables, accepted for publication in A

Famine Early Warning Systems Network (FEWS NET) Land Data Assimilation System (LDAS) and Other Assimilated Hydrological Data at NASA GES DISC

The NASA Goddard Earth Sciences Data and Information Services Center (GES DISC) provides science support for several data sets relevant to agriculture and food security, including the Famine Early Warning Systems Network (FEWS NET) Land Data Assimilation System (LDAS), or FLDAS data set. The GES DISC is one of twelve NASA Earth Observing System (EOS) data centers that process, archive, document, and distribute data from Earth science missions and related projects. The GES DISC hosts a wide range of remote sensing and model data, and provides reliable and robust data access and other services to users worldwide. Beyond data archive and access, the GES DISC offers many services to visualize and analyze the data. This presentation provides a summary of the hydrological data available at the GES DISC, along with an overview of related data services. Specifically, the FLDAS data set has been adapted to work with domains, data streams, and monitoring and forecast requirements associated with food security assessment in data-sparse, developing country settings. The FLDAS global monthly data have a 0.1 x 0.1 degree spatial resolution covering the period from January 1982 to present. Global FLDAS monthly anomaly and monthly climatology data are also available at the GES DISC to evaluate how current conditions compare to averages over the FLDAS 35-year period. Several case studies using the FLDAS soil moisture, evapotranspiration, rainfall, runoff, and surface temperature data will be presented

Micro-Environment Causes Reversible Changes in DNA Methylation and mRNA Expression Profiles in Patient-Derived Glioma Stem Cells

In vitro and in vivo models are widely used in cancer research. Characterizing the similarities and differences between a patient\u27s tumor and corresponding in vitro and in vivo models is important for understanding the potential clinical relevance of experimental data generated with these models. Towards this aim, we analyzed the genomic aberrations, DNA methylation and transcriptome profiles of five parental tumors and their matched in vitro isolated glioma stem cell (GSC) lines and xenografts generated from these same GSCs using high-resolution platforms. We observed that the methylation and transcriptome profiles of in vitro GSCs were significantly different from their corresponding xenografts, which were actually more similar to their original parental tumors. This points to the potentially critical role of the brain microenvironment in influencing methylation and transcriptional patterns of GSCs. Consistent with this possibility, ex vivo cultured GSCs isolated from xenografts showed a tendency to return to their initial in vitro states even after a short time in culture, supporting a rapid dynamic adaptation to the in vitro microenvironment. These results show that methylation and transcriptome profiles are highly dependent on the microenvironment and growth in orthotopic sites partially reverse the changes caused by in vitro culturing

A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis.

ObjectiveEtrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.DesignIn the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).ResultsIn the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.ConclusionEtrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018

Intrinsic Absorption in the Spectrum of NGC 7469: Simultaneous Chandra, FUSE, and STIS Observations

We present simultaneous X-ray, far-ultraviolet, and near-ultraviolet spectra of the Seyfert 1 galaxy NGC 7469 obtained with the Chandra X-Ray Observatory, the Far Ultraviolet Spectroscopic Explorer, and the Space Telescope Imaging Spectrograph on the Hubble Space Telescope. Previous non-simultaneous observations of this galaxy found two distinct UV absorption components, at -560 and -1900 km/s, with the former as the likely counterpart of the X-ray absorber. We confirm these two absorption components in our new UV observations, in which we detect prominent O VI, Ly alpha, N V, and C IV absorption. In our Chandra spectrum we detect O VIII emission, but no significant O VIII or O VII absorption. We also detect a prominent Fe K alpha emission line in the Chandra spectrum, as well as absorption due to hydrogen-like and helium-like neon, magnesium, and silicon at velocities consistent with the -560 km/s UV absorber. The FUSE and STIS data reveal that the H I and C IV column densities in this UV- and X-ray- absorbing component have increased over time, as the UV continuum flux decreased. We use measured H I, N V, C IV, and O VI column densities to model the photoionization state of both absorbers self-consistently. We confirm the general physical picture of the outflow in which the low velocity component is a highly ionized, high density absorber with a total column density of 10^20 cm^-2, located near the broad emission line region, although due to measurable columns of N V and C IV, we assign it a somewhat smaller ionization parameter than found previously, U~1. The high velocity UV component is of lower density, log N=18.6, and likely resides farther from the central engine as we find its ionization parameter to be U=0.08.Comment: Minor correction to abstract; STScI eprint #1683; 50 pages, incl. 19 figures, 4 tables; Accepted to Ap

Assimilated Hydrological Data at NASA GES DISC with Examples of Extreme Events

Extreme weather and climate events, such as heavy rainfall, heatwave, floods and droughts, and strong wind, can have devastating impacts on society. NASA and NOAA, based on independent analyses, recently announced that global surface temperatures in 2018 are the fourth warmest since 1880, behind only those of 2016, 2017, and 2015 (nasa.gov). Also in 2018, the United States experienced 14 billion-dollar disasters, ranking as the fourth highest total number of such events, behind only the years 2017, 2011, and 2016 (climate.gov). Many research studies have focused on acquiring observational and modeling data, to reveal linkages between increasing extreme events, global water and energy cycle, and global climate change. However, draw conclusions is still a challenge. NASA Goddard Earth Sciences Data and Information Services Center is one of twelve NASA Earth Observing System (EOS) data centers that process, archive, document, and distribute data from Earth science missions and related projects. The GES DISC hosts a wide range of remotely-sensed and model data and provides reliable and robust data access and services to users worldwide. This presentation provides a few examples of extreme event study that use Land Surface Model (LSM) assimilated, quality-controlled, and spatially and temporally consistent, hydrological data from the GES DISC. Also provided is a summary table for the hydrological data holdings, along with discussions of recent updates to data and data services