Quantitative Erfassung der motorischen Funktion und körperlichen Aktivität von Patienten mit Multiple Sklerose

Die Multiple Sklerose (MS) ist eine chronisch verlaufende Erkrankung des zentralen Nervensystems und führt u. a. zu einer fortschreitenden Beeinträchtigung der motorischen Funktion sowie zu einer Reduktion der körperlichen Aktivität im Alltag. Um diese Beeinträchtigung klinisch zu erfassen, wird als Goldstandard der Expanded Disability Status Scale (EDSS) durch einen erfahrenen Neurologen erhoben. Dieser steht jedoch zunehmend in der Kritik neben der nicht-quantitativen Erfassung eine erhebliche Untersuchungs- und Untersucher-Variabilität sowie eine geringe Sensitivität gegenüber Veränderungen zu besitzen. In dieser Arbeit werden zwei Geräte (Bewegungssensor und Aktivitätsmesser) als Ergänzung zum EDSS zur Erfassung der motorischen Beeinträchtigung und körperlichen Aktivität von Patienten mit MS vorgestellt. Beide Geräte wurden in einer Patientenkohorte und einer gesunden Vergleichsgruppe getestet. Mit dem Bewegungssensor wurden Gang- und Standanalysen durchgeführt und mit dem Aktivitätsmesser wurde die körperliche Aktivität im Alltag für eine Woche erfasst. Sowohl der Bewegungssensor als auch der Aktivitätsmesser waren in der Lage, signifikante Unterschiede zwischen Patienten und gesunden Kontrollen zu messen. Außerdem korrelierten die Ergebnisse beider Geräte mit dem Grad der neurologischen Beeinträchtigung im EDSS, jedoch nicht untereinander. Die sehr hohen Interkorrelationskoeffizienten bei dreimaliger Messwiederholung des Bewegungssensors unterstreichen dessen hohe Reliabilität. Die Assoziation zwischen den Ergebnissen des Bewegungssensors und dem klinischen Goldstandard, dem EDSS und seinen motorischen Unterkategorien (wie cerebelläres oder Pyramidalsystem), zeigt die Fähigkeit des Bewegungssensors eine klinisch relevante Beeinträchtigung der motorischen Funktion zu erfassen. Ebenfalls ließ sich eine signifikante Assoziation zwischen körperlicher Aktivität und dem EDSS feststellen, jedoch nicht zwischen körperlicher Aktivität und motorischer Funktion. Dies unterstreicht, dass neben der motorischen Funktion noch andere Faktoren einen Einfluss auf die alltägliche Aktivität ausüben. Sowohl der Bewegungssensor als auch der Aktivitätsmesser sind als technische Geräte im Vergleich zu einer neurologischen Untersuchung weniger abhängig vom Untersucher und damit objektiver, einfacher in der Durchführung und auch sensitiver gegenüber subtilen Veränderungen. Da sie zudem mit geringerem personellen Zeitaufwand verbunden sind, sind sie auf lange Sicht kosteneffektiver wodurch auch häufigere Messungen und eine lückenlosere Verlaufsdokumentation möglich werden. Aufgrund der höheren Objektivität und Kosteneffektivität beider Geräte sowie der sehr hohen Reliabilität des Bewegungssensors stellen sie eine geeignete Ergänzung zum EDSS dar und sind daher vermutlich insbesondere für die Verlaufsbeobachtung in klinischen Studien oder auch im klinischen Alltag geeignet. Ferner besitzt die kombinierte Anwendung beider Geräte mit dem EDSS das Potential für eine differenziertere Diagnostik, welche ein umfassenderes Verständnis für die individuelle Beeinträchtigung eines Patienten liefert. Dadurch ergeben sich zukünftig möglicherweise Ansätze für die Entwicklung personalisierter Therapiestrategien.Multiple sclerosis is a chronic disease of the central nervous system that leads to reduced motor function and lower daily physical activity levels. To assess and monitor the extent of neurological disability the patient is most commonly assessed by a physician using the Expanded Disability Status Scale (EDSS). Although the EDSS is being criticized as a non-quantitative measure with low sensitivity to detect changes and reportedly high intra- and inter-rater variability it has remained the gold standard in clinical use. In this work two objective and rater-independent tools are introduced that measure the patient’s motor function and physical activity, an objective motion analysis system and an activity monitor. Both devices are examined in a patient and a healthy age- and gender-matched control group. The motion sensor analyses walking and sway while standing in a controlled environment, while the activity monitor captures physical activity levels during daily routine for a period of one week. Significant differences between patients and controls were observed with both tools. In addition, measurement results from the motion sensor as well as from the activity monitor correlated with the disability grade obtained with the EDSS but not with each other. High intraclass correlation coefficients from the motion analysis system underline its high reliability. Its significant correlation with the clinical gold standard, the EDSS and its motor subscores, shows its ability to represent a clinical significant motor dysfunction. Likewise physical activity levels declined with more severe neurologic impairment represented with the EDSS, but the influence of motor dysfunctions alone on daily physical activity levels was not strong enough to produce a significant correlation and suggests that there are also other factors which have to be taken into consideration. Compared to a neurologic examination both devices are more rater-independent and thus more objective, less complicated and more sensitive to subtle changes. Due to lesser use of personnel resources they are more cost effective and thus enable more measurements with smaller intervals. In conclusion, the high objectivity and cost effectiveness as well as the very high reliability of the motion sensor enable both devices to provide useful and additional valid information to the EDSS in particular for observing long-time changes i.e. in clinical studies or in clinical use. Furthermore as it may be capable of giving a more profound understanding of the patients’ impairments, they might be useful in the future in designing more personalized therapy strategies

Decomposition of a Cooling Plant for Energy Efficiency Optimization Using OptTopo

The operation of industrial supply technology is a broad field for optimization. Industrial cooling plants are often (a) composed of several components, (b) linked using network technology, (c) physically interconnected, and (d) complex regarding the effect of set-points and operating points in every entity. This leads to the possibility of overall optimization. An example containing a cooling tower, water circulations, and chillers entails a non-linear optimization problem with five dimensions. The decomposition of such a system allows the modeling of separate subsystems which can be structured according to the physical topology. An established method for energy performance indicators (EnPI) helps to formulate an optimization problem in a coherent way. The novel optimization algorithm OptTopo strives for efficient set-points by traversing a graph representation of the overall system. The advantages are (a) the ability to combine models of several types (e.g., neural networks and polynomials) and (b) an constant runtime independent from the number of operation points requested because new optimization needs just to be performed in case of plant model changes. An experimental implementation of the algorithm is validated using a simscape simulation. For a batch of five requests, OptTopo needs 61 (Formula presented.) while the solvers Cobyla, SDPEN, and COUENNE need 0.3 min, 1.4 min, and 3.1 min, respectively. OptTopo achieves an efficiency improvement similar to that of established solvers. This paper demonstrates the general feasibility of the concept and fortifies further improvements to reduce computing time

Subjective and objective assessment of physical activity in multiple sclerosis and their relation to health-related quality of life

Background Physical activity (PA) is frequently restricted in people with multiple sclerosis (PwMS) and aiming to enhance PA is considered beneficial in this population. We here aimed to explore two standard methods (subjective plus objective) to assess PA reduction in PwMS and to describe the relation of PA to health-related quality of life (hrQoL). Methods PA was objectively measured over a 7-day period in 26 PwMS (EDSS 1.5–6.0) and 30 matched healthy controls (HC) using SenseWear mini® armband (SWAmini) and reported as step count, mean total and activity related energy expenditure (EE) as well as time spent in PA of different intensities. Measures of EE were also derived from self-assessment with IPAQ (International Physical Activity Questionnaire) long version, which additionally yielded information on the context of PA and a classification into subjects’ PA levels. To explore the convergence between both types of assessment, IPAQ categories (low, moderate, high) were related to selected PA parameters from objective assessment using ANOVA. Group differences and associated effect sizes for all PA parameters as well as their relation to clinical and hrQoL measures were determined. Results Both, SWAmini and IPAQ assessment, captured differences in PA between PwMS and HC. IPAQ categories fit well with common cut-offs for step count (p = 0.002) and mean METs (p = 0.004) to determine PA levels with objective devices. Correlations between specifically matched pairs of IPAQ and SWAmini parameters ranged between r .288 and r .507. Concerning hrQoL, the lower limb mobility subscore was related to four PA measures, while a relation with patients’ report of general contentment was only seen for one. Conclusions Both methods of assessment seem applicable in PwMS and able to describe reductions in daily PA at group level. Whether they can be used to track individual effects of interventions to enhance PA levels needs further exploration. The relation of PA measures with hrQoL seen with lower limb mobility suggests lower limb function not only as a major target for intervention to increase PA but also as a possible surrogate for PA changes

Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta

The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR‐1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta . The synthesis features a decarboxylative cross‐coupling reaction of a sulfonic acid‐containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR‐1A derivatives, including fluorescent and photoaffinity‐based probes, allowed quantification of IOR‐1A, localization studies within S. rosetta cells, and evaluation of structure‐activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta . These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta

Instrumental Assessment of Stepping in Place Captures Clinically Relevant Motor Symptoms of Parkinson’s Disease

Fluctuations of motor symptoms make clinical assessment in Parkinson's disease a complex task. New technologies aim to quantify motor symptoms, and their remote application holds potential for a closer monitoring of treatment effects. The focus of this study was to explore the potential of a stepping in place task using RGB-Depth (RGBD) camera technology to assess motor symptoms of people with Parkinson's disease. In total, 25 persons performed a 40 s stepping in place task in front of a single RGBD camera (Kinect for Xbox One) in up to two different therapeutic states. Eight kinematic parameters were derived from knee movements to describe features of hypokinesia, asymmetry, and arrhythmicity of stepping. To explore their potential clinical utility, these parameters were analyzed for their Spearman's Rho rank correlation to clinical ratings, and for intraindividual changes between treatment conditions using standard response mean and paired t-test. Test performance not only differed between ON and OFF treatment conditions, but showed moderate correlations to clinical ratings, specifically ratings of postural instability (pull test). Furthermore, the test elicited freezing in some subjects. Results suggest that this single standardized motor task is a promising candidate to assess an array of relevant motor symptoms of Parkinson's disease. The simple technical test setup would allow future use by patients themselves

Musical Medien

Prof. Dr. Jens Schröter, Christoph Borbach, Max Kanderske und Prof. Dr. Benjamin Beil sind Herausgeber der Reihe. Die Herausgeber*innen der einzelnen Hefte sind renommierte Wissenschaftler*innen aus dem In- und Ausland.Aktuell ist zu beobachten, dass die Gattung des Musicals vermehrt Einzug in diverse mediale Formate nimmt sowie neue Medien für sich erschließt. Eng verknüpft sind diese medialen Erfahrungen mit Affekten, produziert durch den Kitsch, das Spektakel, die Identifikation, Nahbarkeit und nicht zuletzt die Musikalität des Musicals. Die Ausgabe betrachtet verschiedene Medien, die durch Musicals beeinflusst werden, in denen Musicals stattfinden, die die Form des Musicals durch ihre Medialität verändern oder in denen Musicals Medien umorganisieren. In Anknüpfung an die bisherige Forschung der Musik- und Theaterwissenschaft wird das Musical durch die Rahmung als affektives Artefakt in der Synergie mit diversen medialen Formen für die medienwissenschaftliche Forschung geöffnet. Durch die Interdisziplinarität der Beiträge dient sie als anschlussfähiger Startschuss der Bearbeitung medienwissenschaftlicher Blindflecke der Gattung Musical

Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages

Distinguishing dendritic cells (DCs) from other cells of the mononuclear phagocyte system is complicated by the shared expression of cell surface markers such as CD11c. In this study, we identified Zbtb46 (BTBD4) as a transcription factor selectively expressed by classical DCs (cDCs) and their committed progenitors but not by plasmacytoid DCs (pDCs), monocytes, macrophages, or other lymphoid or myeloid lineages. Using homologous recombination, we replaced the first coding exon of Zbtb46 with GFP to inactivate the locus while allowing detection of Zbtb46 expression. GFP expression in Zbtb46(gfp/+) mice recapitulated the cDC-specific expression of the native locus, being restricted to cDC precursors (pre-cDCs) and lymphoid organ- and tissue-resident cDCs. GFP(+) pre-cDCs had restricted developmental potential, generating cDCs but not pDCs, monocytes, or macrophages. Outside the immune system, Zbtb46 was expressed in committed erythroid progenitors and endothelial cell populations. Zbtb46 overexpression in bone marrow progenitor cells inhibited granulocyte potential and promoted cDC development, and although cDCs developed in Zbtb46(gfp/gfp) (Zbtb46 deficient) mice, they maintained expression of granulocyte colony-stimulating factor and leukemia inhibitory factor receptors, which are normally down-regulated in cDCs. Thus, Zbtb46 may help enforce cDC identity by restricting responsiveness to non-DC growth factors and may serve as a useful marker to identify rare cDC progenitors and distinguish between cDCs and other mononuclear phagocyte lineages