Comparison of circulating tumor cells and AR-V7 as clinical biomarker in metastatic castration-resistant prostate cancer patients

Abstract Biomarker in metastatic castration resistant prostate cancer (mCRPC) treatment are rare. We aimed to compare the clinical value of circulating tumor cells (CTCs) and androgen receptor splice variant 7 (AR-V7) as biomarker in mCRPC patients undergoing androgen receptor-targeted agent (ARTA) treatment. Overall cohort (65 patients) was stratified regarding either CTC or AR-V7 status followed by further sub-stratification of the respective other marker. Subsequently, prostate specific antigen (PSA) response, progression free survival (PFS) and overall survival (OS)) of subgroups was compared. CTCs and AR-V7 were detected in 54 (83%) and 33 (61%) patients, respectively. All AR-V7 + were CTC +. We detected PSA response in all subgroups. For PFS and OS, biomarker stratification revealed differences between all subgroups. Interestingly, no significant differences of AR-V7 transcript copy numbers were detected between responding and non-responding patients. Additionally, multivariable analysis revealed no independent prognostic value of AR-V7 positivity. Both biomarkers show clinical value in prognosticating clinical outcome. Nonetheless, AR-V7 stratification underestimates the heterogenous subgroup of CTC − and CTC + patient, the latter requiring more intense clinical surveillance. Additionally, AR-V7 level does not correlate with clinical response. Thus, the value of AR-V7 as a clinical biomarker must be considered skeptically

Substance Abuse-Related Self-Stigma in Women with Substance Use Disorder and Comorbid Posttraumatic Stress Disorder

Background: Self-stigma is a result of internalizing negative stereotypes by the affected person. Research on self-stigma in substance use disorders (SUD) is still scarce, especially regarding the role of childhood trauma and subsequent posttraumatic disorders. Objectives: The present study investigated the progressive model of self-stigma in women with SUD and posttraumatic stress disorder (PTSD), and the predictive value of PTSD severity and childhood trauma experiences on self-stigma. Method: In a cross-sectional study with 343 women with SUD and PTSD, we used the Self-Stigma in Alcohol Dependency Scale, the Childhood Trauma Questionnaire (CTQ), the PTSD Symptom Scale Interview (PSS-I), and to control for SUD severity and depression, the Addiction Severity Index Lite and the Beck Depression Inventory-II. Hierarchical regression analyses were conducted for each stage of self-stigma (aware-agree-apply-harm). Results: The interrelated successive stages of self-stigma were largely confirmed. In the regression models, no significant effects of the PSS-I- and the CTQ-scores were observed at any stage of self-stigma. Agreeing with negative stereotypes was solely predicted by younger age, applying these stereotypes to oneself was higher in women with younger age, higher depression and SUD severity, and suffering from the application (harm) was only predicted by depression. Conclusions: The progressive model of self-stigma could be confirmed in women with SUD and PTSD, but PTSD severity and childhood trauma did not directly affect this process. Self-stigma appears to be related to depression in a stronger way than PTSD is related to women with SUD and PTSD

Membrane Deployment Technology Development at DLR for Solar Sails and Large-Scale Photovoltaics

Following the highly successful flight of the first interplanetary solar sail, JAXA's IKAROS, with missions in the pipeline such as NASA's NEASCOUT nanospacecraft solar sail and JAXA's Solar Power Sail solar-electric propelled mission to a Jupiter Trojan asteroid, and on the back-ground of the ever increasing power demand of GEO satellites now including all-electric spacecraft, there is renewed interest in large lightweight structures in space. Among these, deployable membrane or 'gossamer' structures can provide very large functional area units for innovative space applications which can be stowed into the limited volumes of launch vehicle fairings as well as secondary payload launch slots, depending on the scale of the mission. Large area structures such as solar sails or high-power photovoltaic generators require a technology that allows their controlled and thereby safe deployment. Before employing such technology for a dedicated science or commercial mission, it is necessary, to demonstrate its reliability, i.e., TRL 6 or higher. A reliable technology that enables controlled deployment was developed in the GOSSAMER-1 solar sail deployment demonstrator project of the German Aerospace Center, DLR, including verification of its functionality with various laboratory tests to qualify the hardware for a first demonstration in low Earth orbit. We provide an overview of the GOSSAMER-1 hardware development and qualification campaign. The design is based on a crossed boom configuration with triangular sail segments. Employing engineering models, all aspects of the deployment were tested under ambient environment. Several components were also subjected to environmental qualification testing. An innovative stowing and deployment strategy for a controlled deployment and the required mechanisms are described. The tests conducted provide insight into the deployment process and allow a mechanical characterization of this process, in particular the measurement of the deployment forces. The stowing and deployment strategy was verified by tests with an engineering qualification model of one out of four GOSSAMER-1 deployment units. According to a test-as-you-fly approach the tests included vibration tests, venting, thermal-vacuum tests and ambient deployment. In these tests the deployment strategy proved to be suitable for a controlled deployment of gossamer spacecraft, and deployment on system level was demonstrated to be robust and controllable. The GOSSAMER-1 solar sail membranes were also equipped with small thin-film photovoltaic arrays intended to supply the core spacecraft. In our follow-on project GOSOLAR, the focus is now entirely on deployment systems for huge thin-film photovoltaic arrays. Based on the GOSSAMER-1 experience, deployment technology and qualification strategies, new technologies for the integration of thin-film photovoltaics are being developed and qualified for a first in-orbit technology demonstration within five years. Main objective is the further development of deployment technology for a 25 m² gossamer solar power generator and a flexible photovoltaic membrane. GOSOLAR enables a wider range of deployment concepts beyond solar sail optimized methods. It uses the S²TEP bus system developed at the Institute of Space Systems as part of the DLR satellite roadmap

Capabilities of Gossamer-1 derived small spacecraft solar sails carrying MASCOT-derived nanolanders for in-situ surveying of NEAs

Any effort which intends to physically interact with specific asteroids requires understanding at least of the composition and multi-scale structure of the surface layers, sometimes also of the interior. Therefore, it is necessary first to characterize each target object sufficiently by a precursor mission to design the mission which then interacts with the object. In small solar system body (SSSB) science missions, this trend towards landing and sample-return missions is most apparent. It also has led to much interest in MASCOT-like landing modules and instrument carriers. They integrate at the instrument level to their mothership and by their size are compatible even with small interplanetary missions. The DLR-ESTEC Gossamer Roadmap NEA Science Working Groups‘ studies identified Multiple NEA Rendezvous (MNR) as one of the space science missions only feasible with solar sail propulsion. Parallel studies of Solar Polar Orbiter (SPO) and Displaced L1 (DL1) space weather early warning missions studies outlined very lightweight sailcraft and the use of separable payload modules for operations close to Earth as well as the ability to access any inclination and a wide range of heliocentric distances. These and many other studies outline the unique capability of solar sails to provide access to all SSSB, at least within the orbit of Jupiter. Since the original MNR study, significant progress has been made to explore the performance envelope of near-term solar sails for multiple NEA rendezvous. However, although it is comparatively easy for solar sails to reach and rendezvous with objects in any inclination and in the complete range of semi-major axis and eccentricity relevant to NEOs and PHOs, it remains notoriously difficult for sailcraft to interact physically with a SSSB target object as e.g. the Hayabusa missions do. The German Aerospace Center, DLR, recently brought the Gossamer solar sail deployment technology to qualification status in the Gossamer-1 project. Development of closely related technologies is continued for very large deployable membrane-based photovoltaic arrays in the GoSolAr project. We expand the philosophy of the Gossamer solar sail concept of efficient multiple sub-spacecraft integration to also include landers for one-way in-situ investigations and sample-return missions. These are equally useful for planetary defence scenarios, SSSB science and NEO utilization. We outline the technological concept used to complete such missions and the synergetic integration and operation of sail and lander. We similarly extend the philosophy of MASCOT and use its characteristic features as well as the concept of Constraints-Driven Engineering for a wider range of operations

Small Spacecraft Based Multiple Near-Earth Asteroid Rendezvous and Landing with Near-Term Solar Sails and ‘Now-Term‘ Technologies

Physical interaction with small solar system bodies (SSSB) is the next step in planetary science, planetary in-situ resource utilization (ISRU), and planetary defense (PD). It requires a broader understanding of the surface properties of the target objects, with particular interest focused on those near Earth. Knowledge of composition, multi-scale surface structure, thermal response, and interior structure is required to design, validate and operate missions addressing these three fields. The current level of understanding is occasionally simplified into the phrase, ”If you’ve seen one asteroid, you’ve seen one asteroid”, meaning that the in-situ characterization of SSSBs has yet to cross the threshold towards a robust and stable scheme of classification. This would enable generic features in spacecraft design, particularly for ISRU and science missions. Currently, it is necessary to characterize any potential target object sufficiently by a dedicated pre-cursor mission to design the mission which then interacts with the object in a complex fashion. To open up strategic approaches, much broader in-depth characterization of potential target objects would be highly desirable. In SSSB science missions, MASCOT-like nano-landers and instrument carriers which integrate at the instrument level to their mothership have met interest. By its size, MASCOT is compatible with small interplanetary missions. The DLR-ESTEC Gossamer Roadmap Science Working Groups‘ studies identified Multiple Near-Earth asteroid (NEA) Rendezvous (MNR) as one of the space science missions only feasible with solar sail propulsion. The Solar Polar Orbiter (SPO) study showed the ability to access any inclination, theDisplaced-L1 (DL1) mission operates close to Earth, where objects of interest to PD and for ISRU reside. Other studies outline the unique capability of solar sails to provide access to all SSSB, at least within the orbit of Jupiter, and significant progress has been made to explore the performance envelope of near-term solar sails for MNR. However, it is difficult for sailcraft to interact physically with a SSSB. We expand and extend the philosophy of the recently qualified DLR Gossamer solar sail deployment technology using efficient multiple sub-spacecraft integration to also include landers for one-way in-situ investigations and sample-return missions by synergetic integration and operation of sail and lander. The MASCOT design concept and its characteristic features have created an ideal counterpart for thisand has already been adapted to the needs of the AIM spacecraft, former part of the NASA-ESA AIDA mission. Designing the combined spacecraft for piggy-back launch accommodation enables low-cost massively parallel access to the NEA population

Solar Sails for Planetary Defense and High-Energy Missions

20 years after the successful ground deployment test of a (20 m)² solar sail at DLR Cologne, and in the light of the upcoming U.S. NEAscout mission, we provide an overview of the progress made since in our mission and hardware design studies as well as the hardware built in the course of our solar sail technology development. We outline the most likely and most efficient routes to develop solar sails for useful missions in science and applications, based on our developed ‘now-term’ and near-term hardware as well as the many practical and managerial lessons learned from the DLR-ESTEC GOSSAMER Roadmap. Mission types directly applicable to planetary defense include single and Multiple NEA Rendezvous ((M)NR) for precursor, monitoring and follow-up scenarios as well as sail-propelled head-on retrograde kinetic impactors (RKI) for mitigation. Other mission types such as the Displaced L1 (DL1) space weather advance warning and monitoring or Solar Polar Orbiter (SPO) types demonstrate the capability of near-term solar sails to achieve asteroid rendezvous in any kind of orbit, from Earth-coorbital to extremely inclined and even retrograde orbits. Some of these mission types such as SPO, (M)NR and RKI include separable payloads. For one-way access to the asteroid surface, nanolanders like MASCOT are an ideal match for solar sails in micro-spacecraft format, i.e. in launch configurations compatible with ESPA and ASAP secondary payload platforms. Larger landers similar to the JAXA-DLR study of a Jupiter Trojan asteroid lander for the OKEANOS mission can shuttle from the sail to the asteroids visited and enable multiple NEA sample-return missions. The high impact velocities and re-try capability achieved by the RKI mission type on a final orbit identical to the target asteroid‘s but retrograde to its motion enables small spacecraft size impactors to carry sufficient kinetic energy for deflection

Small Spacecraft Based Multiple Near-Earth Asteroid Rendezvous and Landing with Near-Term Solar Sails and ‘Now-Term‘ Technologies

Physical interaction with small solar system bodies (SSSB) is the next step in planetary science, planetary in-situ resource utilization (ISRU), and planetary defense (PD). It requires a broader understanding of the surface properties of the target objects, with particular interest focused on those near Earth. Knowledge of composition, multi-scale surface structure, thermal response, and interior structure is required to design, validate and operate missions addressing these three fields. The current level of understanding is occasionally simplified into the phrase, ”If you’ve seen one asteroid, you’ve seen one asteroid”, meaning that the in-situ characterization of SSSBs has yet to cross the threshold towards a robust and stable scheme of classification. This would enable generic features in spacecraft design, particularly for ISRU and science missions. Currently, it is necessary to characterize any potential target object sufficiently by a dedicated pre-cursor mission to design the mission which then interacts with the object in a complex fashion. To open up strategic approaches, much broader in-depth characterization of potential target objects would be highly desirable. In SSSB science missions, MASCOT-like nano-landers and instrument carriers which integrate at the instrument level to their mothership have met interest. By its size, MASCOT is compatible with small interplanetary missions. The DLR-ESTEC Gossamer Roadmap Science Working Groups‘ studies identified Multiple Near-Earth asteroid (NEA) Rendezvous (MNR) as one of the space science missions only feasible with solar sail propulsion. The Solar Polar Orbiter (SPO) study showed the ability to access any inclination, theDisplaced-L1 (DL1) mission operates close to Earth, where objects of interest to PD and for ISRU reside. Other studies outline the unique capability of solar sails to provide access to all SSSB, at least within the orbit of Jupiter, and significant progress has been made to explore the performance envelope of near-term solar sails for MNR. However, it is difficult for sailcraft to interact physically with a SSSB. We expand and extend the philosophy of the recently qualified DLR Gossamer solar sail deployment technology using efficient multiple sub-spacecraft integration to also include landers for one-way in-situ investigations and sample-return missions by synergetic integration and operation of sail and lander. The MASCOT design concept and its characteristic features have created an ideal counterpart for thisand has already been adapted to the needs of the AIM spacecraft, former part of the NASA-ESA AIDA mission. Designing the combined spacecraft for piggy-back launch accommodation enables low-cost massively parallel access to the NEA population

Flights Are Ten a Sail – Re-use and Commonality in the Design and System Engineering of Small Spacecraft Solar Sail Missions with Modular Hardware for Responsive and Adaptive Exploration

The exploration of small solar system bodies started with fast fly-bys of opportunity on the sidelines of missions to the planets. The tiny new worlds seen turned out to be so intriguing and different from all else(and each other) that dedicated sample-return and in-situ analysis missions were developed and launched. Through these, highly efficient low-thrust propulsion expanded from commercial use into mainstream and flagship science missions, there in combination with gravity assists. In parallel, the growth of small spacecraft solutions accelerated in numbers as well as individual spacecraft capabilities. The on-going missions OSIRIS-REx (NASA) or Hayabusa2 (JAXA) with its landers MINERVA-II and MASCOT, and the upcoming NEA scout mission are examples of this synergy of trends. The continuation of these and other related developments towards a propellant-less and highly efficient class of spacecraft for solar system exploration emerges in the form of small spacecraft solar sails designed for carefree handling and equipped with carried landers and application modules. These address the needs of all asteroid user communities– planetary science, planetary defence, and in-situ resource utilization – as well as other fields of solar system science and applications such as space weather warning and solar observations. Already the DLR-ESTEC GOSSAMER Roadmap for Solar Sailing initiated studies of missions uniquely feasible with solar sails such as Displaced L1 (DL1) space weather advance warning and monitoring and Solar Polar Orbiter(SPO) delivery, which demonstrate the capabilities of near-term solar sails to reach any kind of orbit in the inner solar system. This enables Multiple Near-Earth Asteroid (NEA) rendezvous missions (MNR),from Earth-coorbital to extremely inclined and even retrograde target orbits. For these mission types using separable payloads, design concepts can be derived from the separable Boom Sail Deployment Units characteristic of DLR GOSSAMER solar sail technology, nanolanders like MASCOT, or microlanders like the JAXA-DLR Jupiter Trojan Asteroid Lander for the OKEANOS mission which can shuttle from the sail to the targets visited and enable multiple NEA sample-return missions. These nanospacecraft scale components are an ideal match creating solar sails in micro-spacecraft format whose launch configurations are compatible with secondary payload platforms such as ESPA and ASAP. The DLR GOSSAMER solar sail technology builds on the experience gained in the development of deployable membrane structures leading up to the successful ground deployment test of a (20 m) solar sail at DLR Cologne in 1999 and in the 20 years since

Planetary Defense Ground Zero: MASCOT's View on the Rocks - an Update between First Images and Sample Return

At 01:57:20 UTC on October 3rd, 2018, after 3½ years of cruise aboard the JAXA spacecraft HAYABUSA2 and about 3 months in the vicinity of its target, the MASCOT lander was separated successfully by from an altitude of 41 m. After a free-fall of only ~5m51s MASCOT made first contact with C-type near-Earth and potentially hazardous asteroid (162173) Ryugu, by hitting a big boulder. MASCOT then bounced for ~11m3s, in the process already gathering valuable information on mechanical properties of the surface before it came to rest. It was able to perform science measurements at 3 different locations on the surface of Ryugu and took many images of its spectacular pitch-black landscape. MASCOT’s payload suite was designed to investigate the fine-scale structure, multispectral reflectance, thermal characteristics and magnetic properties of the surface. Somewhat unexpectedly, MASCOT encountered very rugged terrain littered with large surface boulders. Observing in-situ, it confirmed the absence of fine particles and dust as already implied by the remote sensing instruments aboard the HAYABUSA2 spacecraft. After some 17h of operations, MASCOT‘s mission ended with the last communication contact as it followed Ryugu’s rotation beyond the horizon as seen from HAYABUSA2. Soon after, its primary battery was depleted. We present a broad overview of the recent scientific results of the MASCOT mission from separation through descent, landing and in-situ investigations on Ryugu until the end of its operation and relate them to the needs of planetary defense interactions with asteroids. We also recall the agile, responsive and sometimes serendipitous creation of MASCOT, the two-year rush of building and delivering it to JAXA’s HAYABUSA2 spacecraft in time for launch, and the four years of in-flight operations and on-ground testing to make the most of the brief on-surface mission