David Hume als therapeutischer Philosoph. Eine Auflösung der Induktionsproblematik mit wittgensteinianischer Methode.

Ziel der Arbeit ist zu zeigen, dass sich in der theoretischen Philosophie David Humes Ansätze zu einer therapeutischen Methode finden, wie sie von Ludwig Wittgenstein angewandt und beschrieben wurde. Im ersten Teil wird Wittgensteins Konzeption der Philosophie und ihre Anwendung anhand einer genauen Textexegese dargestellt. Der zweite Teil untersucht primär die Humeschen Überlegungen zu Kausalität und Induktion, seine methodologischen Aussagen sowie seine Perzeptionstheorie und argumentiert für die These, dass Hume ebenfalls, wenn auch mit Einschränkungen, Elemente einer therapeutischen Methode und eine entsprechende Konzeption der Philosophie zugeschrieben werden können

Early detection of brain metastases in a supervised exercise program for patients with advanced breast cancer : A case report

Introduction Around 25% of metastatic breast cancer (mBC) patients develop brain metastases, which vastly affects their overall survival and quality of life. According to the current clinical guidelines, regular magnetic resonance imaging screening is not recommended unless patients have recognized central nervous system–related symptoms. Patient Presentation The patient participated in the EFFECT study, a randomized controlled trial aimed to assess the effects of a 9-month structured, individualized and supervised exercise intervention on quality of life, fatigue and other cancer and treatment-related side effects in patients with mBC. She attended the training sessions regularly and was supervised by the same trainer throughout the exercise program. In month 7 of participation, her exercise trainer detected subtle symptoms (e.g., changes in movement pattern, eye movement or balance), which had not been noticed or reported by the patient herself or her family, and which were unlikely to have been detected by the oncologist or other health care providers at that point since symptoms were exercise related. When suspicion of brain metastases was brought to the attention of the oncologist by the exercise trainer, the response was immediate, and led to early detection and treatment of brain metastases. Conclusion and clinical implications The brain metastases of this patient were detected earlier due to the recognition of subtle symptoms detected by her exercise trainer and the trust and rapid action by the clinician. The implementation of physical exercise programs for cancer patients requires well-trained professionals who know how to recognize possible alterations in patients and also, good communication between trainers and the medical team to enable the necessary actions to be taken

Early Detection of Brain Metastases in a Supervised Exercise Program for Patients with Advanced Breast Cancer: A Case Report

INTRODUCTION: Around 25% of metastatic breast cancer (mBC) patients develop brain metastases, which vastly affects their overall survival and quality of life. According to the current clinical guidelines, regular magnetic resonance imaging screening is not recommended unless patients have recognized central nervous system-related symptoms. PATIENT PRESENTATION: The patient participated in the EFFECT study, a randomized controlled trial aimed to assess the effects of a 9-month structured, individualized and supervised exercise intervention on quality of life, fatigue and other cancer and treatment-related side effects in patients with mBC. She attended the training sessions regularly and was supervised by the same trainer throughout the exercise program. In month 7 of participation, her exercise trainer detected subtle symptoms (e.g., changes in movement pattern, eye movement or balance), which had not been noticed or reported by the patient herself or her family, and which were unlikely to have been detected by the oncologist or other health care providers at that point since symptoms were exercise related. When suspicion of brain metastases was brought to the attention of the oncologist by the exercise trainer, the response was immediate, and led to early detection and treatment of brain metastases. CONCLUSION AND CLINICAL IMPLICATIONS: The brain metastases of this patient were detected earlier due to the recognition of subtle symptoms detected by her exercise trainer and the trust and rapid action by the clinician. The implementation of physical exercise programs for cancer patients requires well-trained professionals who know how to recognize possible alterations in patients and also, good communication between trainers and the medical team to enable the necessary actions to be taken

Exercise recommendations for people with bone metastases: Expert consensus for healthcare providers and clinical exercise professionals

Purpose: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion. Methods: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement. Results: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment–related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential. Conclusion: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases

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

CFH, C3 and ARMS2 Are Significant Risk Loci for Susceptibility but Not for Disease Progression of Geographic Atrophy Due to AMD

Age-related macular degeneration (AMD) is a prevalent cause of blindness in Western societies. Variants in the genes encoding complement factor H (CFH), complement component 3 (C3) and age-related maculopathy susceptibility 2 (ARMS2) have repeatedly been shown to confer significant risks for AMD; however, their role in disease progression and thus their potential relevance for interventional therapeutic approaches remains unknown. Here, we analyzed association between variants in CFH, C3 and ARMS2 and disease progression of geographic atrophy (GA) due to AMD. A quantitative phenotype of disease progression was computed based on longitudinal observations by fundus autofluorescence imaging. In a subset of 99 cases with pure bilateral GA, variants in CFH (Y402H), C3 (R102G), and ARMS2 (A69S) are associated with disease (P = 1.6x10(-9), 3.2x10(-3), and P = 2.6x10(-12), respectively) when compared to 612 unrelated healthy control individuals. In cases, median progression rate of GA over a mean follow-up period of 3.0 years was 1.61 mm(2)/year with high concordance between fellow eyes. No association between the progression rate and any of the genetic risk variants at the three loci was observed (P>0.13). This study confirms that variants at CFH, C3, and ARMS2 confer significant risks for GA due to AMD. In contrast, our data indicate no association of these variants with disease progression which may have important implications for future treatment strategies. Other, as yet unknown susceptibilities may influence disease progression

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

Distribution Analysis of Hydrogenases in Surface Waters of Marine and Freshwater Environments

Background Surface waters of aquatic environments have been shown to both evolve and consume hydrogen and the ocean is estimated to be the principal natural source. In some marine habitats, H2 evolution and uptake are clearly due to biological activity, while contributions of abiotic sources must be considered in others. Until now the only known biological process involved in H2 metabolism in marine environments is nitrogen fixation. Principal Findings We analyzed marine and freshwater environments for the presence and distribution of genes of all known hydrogenases, the enzymes involved in biological hydrogen turnover. The total genomes and the available marine metagenome datasets were searched for hydrogenase sequences. Furthermore, we isolated DNA from samples from the North Atlantic, Mediterranean Sea, North Sea, Baltic Sea, and two fresh water lakes and amplified and sequenced part of the gene encoding the bidirectional NAD(P)-linked hydrogenase. In 21% of all marine heterotrophic bacterial genomes from surface waters, one or several hydrogenase genes were found, with the membrane-bound H2 uptake hydrogenase being the most widespread. A clear bias of hydrogenases to environments with terrestrial influence was found. This is exemplified by the cyanobacterial bidirectional NAD(P)-linked hydrogenase that was found in freshwater and coastal areas but not in the open ocean. Significance This study shows that hydrogenases are surprisingly abundant in marine environments. Due to its ecological distribution the primary function of the bidirectional NAD(P)-linked hydrogenase seems to be fermentative hydrogen evolution. Moreover, our data suggests that marine surface waters could be an interesting source of oxygen-resistant uptake hydrogenases. The respective genes occur in coastal as well as open ocean habitats and we presume that they are used as additional energy scavenging devices in otherwise nutrient limited environments. The membrane-bound H2-evolving hydrogenases might be useful as marker for bacteria living inside of marine snow particles