Joachim Latsch

Short Radius Centrifuges - A New Approach for Life Science Experiments under Hyper-g Conditions for Applications in Space and Beyond

A broad variety of countermeasures on the effects of weightlessness on human physiology have been developed and applied in the course of space exploration. Devices like treadmills, stretch ropes etc. have several disadvantages in common: they require a significant amount of crew time and they may not efficiently counteract the degradation of physiological structures and cellular functions. Some methods even include potentially painful or uncomfortable procedures for the astronauts. Thus, the application of Artificial Gravity (AG) generated by short radius centrifuges (they fit into space vessels) has been discussed and proposed by a number of scientists and space agencies as an alternative countermeasure during long-term space missions. Although there is a profound knowledge concerning, e.g., the cardiovascular system and immune responses acquired on long radius centrifuges, there is a remarkable lack of knowledge concerning the same issues on devices operating with short radius. In strict contrast to long radius centrifuges, there is a significant gravity gradient in the head-to-toe axis which comes along with the short radius and higher relative rotation velocity. Thus it is of utmost importance to continue investigating the effects of AG, especially by use of short radius centrifuges. The Short Arm Human Centrifuge (SAHC) at the German Aerospace Center (DLR) in Cologne, Germany, is the most advanced type of short radius centrifuges presently commercially available. Experience gained so far using the SAHC at DLR revealed that future projects on centrifuge devices with short radius should aim at a clear identification of the threshold level of the g-load, which is necessary to efficiently counteract the degradation of physical structures and an efficient support of cellular functions. A satisfying result would be combined countermeasure methods applied at a threshold concerning g-load and exposition time in the course of long-term sojourn in microgravity. Another future control or monitoring method to exactly dose AG training is heart rate variability, which offers an insight into neurovegetative and cardiovascular regulation. Centrifuges like the SAHC are also useful platforms to accommodate small biological experiments, e.g., experiments addressing the response of cultured cells to hypergravity. Here, we briefly review the issue of short radius centrifuges and also address our experience hitherto gained during a number of scientific projects carried out at the SAHC at DLR.

Impact of a half marathon on cellular immune system, pro-inflammatory cytokine levels, and recovery behavior of breast cancer patients in the aftercare compared to healthy controls

Exercise has beneficial effects on cancer prevention as well as on prognosis of patients with cancer. To optimize the outcomes of exercise programs, more knowledge about the underlying mechanisms is needed. This study investigates the short‐term effects of a half marathon on immune cell proportions, pro‐inflammatory cytokine levels, and recovery behavior of patients with breast cancer in the aftercare compared to healthy controls.

Substantial improvement of primary cardiovascular prevention by a systematic score-based multimodal approach: A randomized trial: The PreFord-Study

Trial design Prospective randomized multicentre interventional study. Methods Individual cardiovascular risk assessment in Ford Company, Germany employees (n = 4.196), using the European Society of Cardiology-Systematic Coronary Risk Evaluation (ESC-SCORE) for classification into three risk groups. Subjects assigned to ESC high-risk group (ESC-SCORE ≥ 5%), without a history of cardiovascular disease were eligible for randomization to a multimodal 15-week intervention programme (INT) or to usual care and followed up for 36 months. Objectives Evaluation of the long-term effects of a risk-adjusted multimodal intervention in high-risk subjects. Primary endpoint: reduction of ESC-SCORE in INT versus usual care. Secondary endpoints: composite of fatal and non-fatal cardiovascular events and time to first cardiovascular event. Statistical analysis: intention-to-treat and per-protocol analysis. Results Four hundred and forty-seven subjects were randomized to INT (n = 224) or to usual care (n = 223). After 36 months ESC-SCORE development favouring INT was observed (INT: 8.70% to 10.03% vs. usual care: 8.49% to 12.09%; p = 0.005; net difference: 18.50%). Moreover, a significant reduction in the composite cardiovascular events was observed: (INT: n = 11 vs. usual care: n = 27). Hazard ratio of intervention versus control was 0.51 (95% confidence interval 0.25–1.03; p = 0.062) in the intention-to-treat analysis and 0.41 (95% confidence interval 0.18–0.90; p = 0.026) in the per-protocol analysis, respectively. No intervention-related adverse events or side-effects were observed. Conclusions Our results demonstrate the efficiency of identifying cardiovascular high-risk subjects by the ESC-SCORE in order to enrol them to a risk adjusted primary prevention programme. This strategy resulted in a significant improvement of ESC-SCORE, as well as a reduction in predefined cardiovascular endpoints in the INT within 36 months. (ISRCTN 23536103.)

Heart Rate and Oxygen Uptake Kinetics in Type 2 Diabetes Patients – A Pilot Study on the Influence of Cardiovascular Medication on Regulatory Processes

The aim of this pilot study was to investigate whether there are differences in heart rate and oxygen uptake kinetics in type 2 diabetes patients, considering their cardiovascular medication. It was hypothesized that cardiovascular medication would affect heart rate and oxygen uptake kinetics and that this could be detected using a standardized exercise test. 18 subjects were tested for maximal oxygen uptake. Kinetics were measured in a single test session with standardized, randomized moderate-intensity work rate changes. Time series analysis was used to estimate kinetics. Greater maxima in cross-correlation functions indicate faster kinetics. 6 patients did not take any cardiovascular medication, 6 subjects took peripherally acting medication and 6 patients were treated with centrally acting medication. Maximum oxygen uptake was not significantly different between groups. Significant main effects were identified regarding differences in muscular oxygen uptake kinetics and heart rate kinetics. Muscular oxygen uptake kinetics were significantly faster than heart rate kinetics in the group with no cardiovascular medication (maximum in cross-correlation function of muscular oxygen uptake vs. heart rate; 0.32±0.08 vs. 0.25±0.06; p=0.001) and in the group taking peripherally acting medication (0.34±0.05 vs. 0.28±0.05; p=0.009) but not in the patients taking centrally acting medication (0.28±0.05 vs. 0.30±0.07; n.s.). It can be concluded that regulatory processes for the achievement of a similar maximal oxygen uptake are different between the groups. The used standardized test provided plausible results for heart rate and oxygen uptake kinetics in a single measurement session in this patient group.The aim of this pilot study was to investigate whether there are differences in heart rate and oxygen uptake kinetics in type 2 diabetes patients, considering their cardiovascular medication. It was hypothesized that cardiovascular medication would affect heart rate and oxygen uptake kinetics and that this could be detected using a standardized exercise test. 18 subjects were tested for maximal oxygen uptake. Kinetics were measured in a single test session with standardized, randomized moderate-intensity work rate changes. Time series analysis was used to estimate kinetics. Greater maxima in cross-correlation functions indicate faster kinetics. 6 patients did not take any cardiovascular medication, 6 subjects took peripherally acting medication and 6 patients were treated with centrally acting medication. Maximum oxygen uptake was not significantly different between groups. Significant main effects were identified regarding differences in muscular oxygen uptake kinetics and heart rate kinetics. Muscular oxygen uptake kinetics were significantly faster than heart rate kinetics in the group with no cardiovascular medication (maximum in cross-correlation function of muscular oxygen uptake vs. heart rate; 0.32±0.08 vs. 0.25±0.06; p=0.001) and in the group taking peripherally acting medication (0.34±0.05 vs. 0.28±0.05; p=0.009) but not in the patients taking centrally acting medication (0.28±0.05 vs. 0.30±0.07; n.s.). It can be concluded that regulatory processes for the achievement of a similar maximal oxygen uptake are different between the groups. The used standardized test provided plausible results for heart rate and oxygen uptake kinetics in a single measurement session in this patient group.

Effects of Cycling and Exergaming on Neurotrophic Factors in Elderly Type 2 Diabetic Men – A Preliminary Investigation

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing neurodegenerative diseases. There is growing evidence that repeated exercise-induced transient increases in neurotrophic factors can augment neurogenesis and neuroplasticity. This pilot study compares the effects of 30-min submaximal cycling with those of exergaming (combining exercise and video gaming) at the same duration and same rating of perceived exertion (BORG RPE: 14-15) on serum neurotrophic factors in 8 elderly non-insulin-dependent T2DM patients (71±4 years) (2×2 crossover design). Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-1 levels were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Heart rates were almost equal during cycling and exergaming, while lactate values were significantly higher during cycling (cycling versus exergaming: 3.7±1.1 versus 2.5±1.2 mmol/l, p<0.05). BDNF and VEGF levels were increased significantly post-cycling (+20%,+14%, p<0.05). No other significant pre-post changes were evident. This study demonstrates that acute exercise can increase neurotrophic factors (BDNF, VEGF) in elderly T2DM patients, depending on exercise mode.

Die PräFord-Studie

The PreFord Study is a multicenter prospective cohort study to evaluate guideline based risk management on primary prevention of cardiovascular diseases. Furthermore a randomised controlled trial (RCT) will be designed to analyse the effect of a special intervention program. 40 000 employees of the Ford Motor Company, Visteon Company and Deutz Company in Germany will be included, monitored for ten years and the following primary endpoints will be investigated: 1. evaluation and comparison of established and newly developed risk-scores 2. the relative impact of single and combined cardiovascular risk factors on cardiovascular diseases 3. the influence of a novel occupationally integrated ambulant rehabilitation program in combination with a guideline oriented optimal drug therapy within a high risk group on the primary endpoint: risk reduction by 4. the influence of this intervention on secondary endpoints: death, myocardial infarction and stroke, combined appearance of angina pectoris and hospitalisation, occurence of cerebral circulatory disorder and hospitalisation, ocurrence of peripheral occlusive arterial disease and hospitalisation and single cardiovascular risk factors and cost-benefit-analysis. Beginning with an cross sectional study there will be a systemic screening of cardiovascular risk profiles, of anthropometric data and different lifestyle-factors. Based on these data participants will be differentiated into three risk-groups according to the risk score of the European Society of Cardiology (risk of a lethal primary acute cardiovascular event: I ≤ 1%; II > 1–< 5% and III ≥ 5%). In the following longitudinal study different strategies will be applied: Group I: low risk (< 0.5% per year): repetition of the investigation after five and ten years. Group II: middle risk, (0.6% to 1.4% per year), repetition of the investigation every two years, instruction of the patients general practitioner (GP) with respect to a risk factor oriented and evidence based treatment. Group III: high risk, (> 1.5% per year or >15% within the next 10 years) will be randomised into two interventional groups. The first one, the intervention-group “PreFord” will perform an occupational integrated rehabilitation program (2,5–3 hours twice a week, for 15 weeks according to the BAR guidelines) with a following engagement in heart-groups and an annual repetition of the check-ups. The second group, the “classic” intervention-group will be treated evidence based in cooperation with their GP. As a result of this long term interventional study efficient, area wide implementable and economically feasible prevention concepts with special regards to operational healthcare will be developed and evaluated. Core elements will be exercise- and lifestyle-oriented concepts as well as guideline-based pharmacotherapy. Die Prä-Ford-Studie ist eine prospektive Kohortenstudie zur Bewertung von leitlinienorientierten Maßnahmen zur Primärprävention von Herz-Kreislauf-Erkrankungen (HKE). Zusätzlich soll für eine Teilkohorte (kardiovaskuläres Hochrisikoprofil) im Rahmen einer randomisierten, kontrollierten, klinischen Studie (RCT) der Effekt einer speziellen Interventionsmaßnahme analysiert werden; die Planung und Durchführung dieses Studienteils erfolgt gesondert auf der Basis einschlägiger Empfehlungen zur „good clinical practice“ (GCP). Insgesamt sollen auf der Basis der Verlaufsdaten von rund 40 000 Mitarbeitern der Ford-Werke AG, der Deutz AG und der Visteon Deutschland GmbH über einen Zeitraum von 10 Jahren folgende Fragestellungen untersucht werden: 1. Evaluation und Vergleich etablierter und neuentwickelter Risikoscores. 2. Relative Bedeutung einzelner Risikofaktoren und deren Kombination für die Entwicklung von Herz-Kreislauf-Erkrankungen. 3. Einfluss eines neu konzipierten, berufsbegleitenden ambulanten Rehabilitationsprogrammes in Verbindung mit einer leitlinienorientierten, optimalen medikamentösen Therapie bei einer Hochrisikogruppe auf den primären Endpunkt: Senkung des absoluten Risikos im ersten Jahr sowie in zehn Jahren. 4. Einfluss der Intervention auf die sekundären Endpunkte: Tod, Myokardinfarkt, Schlaganfall, kombiniertes Auftreten von Angina Pectoris und Krankenhauseinweisung, Auftreten zerebraler Durchblutungsstörungen und Krankenhauseinweisung und Auftreten von pAVK und Krankenhauseinweisung, sowie einzelne kardiovaskuläre Risikofaktoren und Kosten-Nutzen-Analysen. Hierzu werden zunächst in einer Querschnittsstudie das kardiovaskuläre Risikoprofil, anthropometrische Daten, sowie verschiedene Lebensstilfaktoren im Rahmen eines systematischen Screenings erfasst. Auf dieser Datenbasis erfolgt nach dem Score der Europäischen Gesellschaft für Kardiologie eine Einteilung in drei Risikogruppen: geringes, mittleres, hohes Risiko (das Risiko für ein fatales Akutereignis ist ≤ 1%; >1–< 5% bzw. ≥ 5% in 10 Jahren [12]. Im Rahmen der anschließenden Longitudinalstudie ist das weitere Vorgehen in der Gruppe I (geringes Risiko): Wiederholung der Screening-Untersuchung nach 5 und 10 Jahren; in der Gruppe II (mittleres Risiko): Screening-Untersuchungen alle 2 Jahre sowie Beratung und Kooperation mit dem Hausarzt mit dem Ziel eines leitlinienorientierten Risikomanagements. Die Gruppe III (hohes Risiko) wird entweder in eine Interventionsgruppe „PräFord“ oder in eine Interventionsgruppe „klassisch“ randomisiert. Der Interventionsgruppe „PräFord“ wird eine ambulante kardiologische Rehabilitationsmaßnahme angeboten (berufsbegleitend über 15 Wochen, zweimal wöchentlich 2,5–3 Stunden; Inhalte und Qualität nach den Rahmenempfehlungen der Bundesarbeitsgemeinschaft für Rehabilitation) [11] mit anschließender Weiterbetreuung in Herzgruppen und jährlichen Nachuntersuchungen über 10 Jahre. Der Interventionsgruppe „klassisch“ werden in Absprache mit den jeweiligen Hausärzten alle verfügbaren konventionellen Maßnahmen, Behandlungen und Informationen mit Ausnahme der berufsbegleitenden Rehabilitation angeboten. Die statistische Planung dieses Studienteils erfolgt gesondert. Im Ergebnis dieser Langzeitstudie sollen—auch unter ökonomischen Gesichtspunkten—effiziente und flächendeckend implementierbare Konzepte kardiovaskulärer Primärprävention dargestellt werden.

Enhancement of Direct Augmented Reality Object Selection by Gravity-Adapted Target Resizing

Direct object selection in an Augmented Reality environment that is coded outside of human body frame of reference is deteriorated under short-term altered gravity. As countermeasures we developed a gravity-adapted resizing technique based on the Hooke’s law that resulted in two techniques of target and interface deformation (compression, elongation). To prove the concept of this resizing approach we initially conducted two experiments under simulated hypergravity conditions. While during the first study hypergravity was induced by a long-arm human centrifuge, in the second study hypergravity was simulated by additional arm weightings that were balanced and attached to the participants’ pointing arm. We investigated the difference of the task performance with respect to the pointing frequency, response time, pointing speed and accuracy, when participants performed a visuomotor task under the resizing conditions compared to the unchanged condition. During the second study we additionally evaluated the speed-accuracy tradeoff of the resizing techniques according to Fitts’ law and the physiological workload by cardiac responses analyzing the heart rate variability. Both experiments showed that the online adaption of the present gravity load to targets’ size and distance influences the performance of direct AR direct pointing. The results revealed that the pointing performance benefits from elongation target deformation by increased target sizes and distances, while pointing towards compressed targets mostly decreases the physiological workload under increased gravity conditions.

The impact of altered gravitation on performance and workload of augmented reality hand-eye-coordination: inside vs. outside of human body frame of reference

We investigated new interface technologies to ease astronauts work under altered gravity. By bridging the gap between the physical reality and digital information, Augmented Reality keeps the focus on the task to fulfill. It is important that the operation of such Augmented Reality supported assistant systems is adequate preserved in weightlessness. By distinguishing the interface alignment to the body and outside of the body this paper presents a user study conducted to quantify and qualify the impact of altered gravity on sensorimotor hand-eye coordination related to the human body frame of reference. Taking the advantages of parabolic flights, we compared the performance of this alignment methods under normo- and altered gravity. Beside of verified effects of altered gravity on aimed pointing movements, the study showed a higher efficiency and decreased workload for the body aligned condition.

Welche nicht-medikamentösen Maßnahmen sind sinnvoll?

Regelmäßige körperliche/sportliche Aktivität, langfristige Ernährungsumstellung und Gewichtsreduktion, die vor allem das Abschmelzen abdomineller Fettpolster zum Ziel hat: Diese Maßnahmen werden bei Hypertonie sowie präventiv bei Prähypertonus dringend empfohlen. Am besten wirken sie kombiniert, unter ärztlicher Steuerung und in Zusammenarbeit mit Bewegungs- und Verhaltenstherapeuten.

:enviFuge - A Novel Approach for Space Medicine and Life Science Experiments

The application of AG generated by short diameter centrifuges has been proposed by a number of scientists and space agencies as a countermeasure against microgravity induced physiological degradation during long-term space missions, e.g. to Mars. The major objective of :enviFuge is to obtain extensive knowledge of hypergravity effects on the cardiovascular system, the cardio-vegetative regulation, the orthostatic regulation and other physiological systems. Therefore a unique research and training device, the :enviFuge, has been defined by DLR and developed by AMST Systemtechnik GmbH, and is located at DLR’s brand-new :envihab in Cologne. Operation of this multipurpose research and training centrifuge started in the middle of 2013. :enviFuge features multiple research