Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): multicentre, randomised controlled, endpoint blinded trial

OBJECTIVE: To determine the safety and efficacy of aerobic exercise on activities of daily living in the subacute phase after stroke. DESIGN: Multicentre, randomised controlled, endpoint blinded trial. SETTING: Seven inpatient rehabilitation sites in Germany (2013-17). PARTICIPANTS: 200 adults with subacute stroke (days 5-45 after stroke) with a median National Institutes of Health stroke scale (NIHSS, range 0-42 points, higher values indicating more severe strokes) score of 8 (interquartile range 5-12) were randomly assigned (1:1) to aerobic physical fitness training (n=105) or relaxation sessions (n=95, control group) in addition to standard care. INTERVENTION: Participants received either aerobic, bodyweight supported, treadmill based physical fitness training or relaxation sessions, each for 25 minutes, five times weekly for four weeks, in addition to standard rehabilitation therapy. Investigators and endpoint assessors were masked to treatment assignment. MAIN OUTCOME MEASURES: The primary outcomes were change in maximal walking speed (m/s) in the 10 m walking test and change in Barthel index scores (range 0-100 points, higher scores indicating less disability) three months after stroke compared with baseline. Safety outcomes were recurrent cardiovascular events, including stroke, hospital readmissions, and death within three months after stroke. Efficacy was tested with analysis of covariance for each primary outcome in the full analysis set. Multiple imputation was used to account for missing values. RESULTS: Compared with relaxation, aerobic physical fitness training did not result in a significantly higher mean change in maximal walking speed (adjusted treatment effect 0.1 m/s (95% confidence interval 0.0 to 0.2 m/s), P=0.23) or mean change in Barthel index score (0 (-5 to 5), P=0.99) at three months after stroke. A higher rate of serious adverse events was observed in the aerobic group compared with relaxation group (incidence rate ratio 1.81, 95% confidence interval 0.97 to 3.36). CONCLUSIONS: Among moderately to severely affected adults with subacute stroke, aerobic bodyweight supported, treadmill based physical fitness training was not superior to relaxation sessions for maximal walking speed and Barthel index score but did suggest higher rates of adverse events. These results do not appear to support the use of aerobic bodyweight supported fitness training in people with subacute stroke to improve activities of daily living or maximal walking speed and should be considered in future guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT01953549

Quasi-Monte Carlo rules for numerical integration over the unit sphere S2\mathbb{S}^2

We study numerical integration on the unit sphere $\mathbb{S}^2 \subset \mathbb{R}^3$ using equal weight quadrature rules, where the weights are such that constant functions are integrated exactly. The quadrature points are constructed by lifting a $(0,m,2)$-net given in the unit square $[0,1]^2$ to the sphere $\mathbb{S}^2$ by means of an area preserving map. A similar approach has previously been suggested by Cui and Freeden [SIAM J. Sci. Comput. 18 (1997), no. 2]. We prove three results. The first one is that the construction is (almost) optimal with respect to discrepancies based on spherical rectangles. Further we prove that the point set is asymptotically uniformly distributed on $\mathbb{S}^2$. And finally, we prove an upper bound on the spherical cap $L_2$-discrepancy of order $N^{-1/2} (\log N)^{1/2}$ (where $N$ denotes the number of points). This slightly improves upon the bound on the spherical cap $L_2$-discrepancy of the construction by Lubotzky, Phillips and Sarnak [Comm. Pure Appl. Math. 39 (1986), 149--186]. Numerical results suggest that the $(0,m,2)$-nets lifted to the sphere $\mathbb{S}^2$ have spherical cap $L_2$-discrepancy converging with the optimal order of $N^{-3/4}$

Cardiac and Respiratory Patterns Synchronize between Persons during Choir Singing

Dyadic and collective activities requiring temporally coordinated action are likely to be associated with cardiac and respiratory patterns that synchronize within and between people. However, the extent and functional significance of cardiac and respiratory between-person couplings have not been investigated thus far. Here, we report interpersonal oscillatory couplings among eleven singers and one conductor engaged in choir singing. We find that: (a) phase synchronization both in respiration and heart rate variability increase significantly during singing relative to a rest condition; (b) phase synchronization is higher when singing in unison than when singing pieces with multiple voice parts; (c) directed coupling measures are consistent with the presence of causal effects of the conductor on the singers at high modulation frequencies; (d) the different voices of the choir are reflected in network analyses of cardiac and respiratory activity based on graph theory. Our results suggest that oscillatory coupling of cardiac and respiratory patterns provide a physiological basis for interpersonal action coordination

Classificatory Theory in Data-Intensive Science: The Case of Open Biomedical Ontologies

publication-status: Publishedtypes: ArticleThis is the author's version of a paper that was subsequently published in International Studies in the Philosophy of Science. Please cite the published version by following the DOI link.Knowledge-making practices in biology are being strongly affected by the availability of data on an unprecedented scale, the insistence on systemic approaches and growing reliance on bioinformatics and digital infrastructures. What role does theory play within data-intensive science, and what does that tell us about scientific theories in general? To answer these questions, I focus on Open Biomedical Ontologies, digital classification tools that have become crucial to sharing results across research contexts in the biological and biomedical sciences, and argue that they constitute an example of classificatory theory. This form of theorizing emerges from classification practices in conjunction with experimental know-how and expresses the knowledge underpinning the analysis and interpretation of data disseminated online.Economic and Social Research Council (ESRC)The British AcademyLeverhulme Trus

Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben

Fragestellung: Sowohl die Childhood Group der International Obesity Task Force (IOTF) als auch die European Childhood Obesity Group (ECOG) empfehlen den Body-mass-Index als Beurteilungskriterium für Übergewicht und Adipositas bei Kindern und Jugendlichen. Im Erwachsenenalter erfolgt die Definition von Übergewicht und Adipositas anhand fester Grenzwerte, bei der Beurteilung von Kindern und Jugendlichen müssen die alters- und geschlechtsspezifischen Veränderungen des BMI berücksichtigt werden. Methode: Unter Heranziehung von 17 bereits durchgeführten Untersuchungen aus verschiedenen Regionen Deutschlands wurden BMI-Perzentile für Kinder und Jugendliche erstellt. Die Berechnung der Perzentile basiert auf den Körperhöhen- und Körpergewichtsdaten von 17.147 Jungen und 17.275 Mädchen im Alter von 0–18 Jahren. Ergebnisse und Schlussfolgerung: Die vorgestellten Perzentile sollten als Referenz für deutsche Kinder und Jugendliche angewendet werden. Die Arbeitsgemeinschaft „Adipositas im Kindes- und Jugendalter“ (AGA) hat in ihren Leitlinien die Anwendung der hier vorgestellten 90. und 97. Perzentile zur Definition von Übergewicht und Adipositas empfohlen.Objectives: Both the Childhood Group of the International Obesity Task Force (IOTF) and the European Childhood Obesity Group (ECOG) recommend to use the body mass index (BMI = weight in kilograms/height in meter2) to evaluate overweight and obesity in children and adolescents. Whereas it is customary with adults to use fixed cut off points to define overweight and obesity, in children and adolescents age and sex specific developmental changes in BMI need to be addressed, which are due to physiological alterations of fat mass. Method: Because a national reference population for children and adolescents does not exist in Germany, a BMI reference data set was compiled. Therefore measurements of height and weight from 17 different regional studies including 17147 boys and 17275 girls aged 0 to 18 years were used. Results and conclusions: We recommend the use of the presented percentiles as reference to asses under- and overweight (obesity) in German children and adolescents. In the guidelines of the “Arbeitsgruppe Adipositas im Kindes- und Jugendalter”(AGA) the 90th and 97th BMI percentiles as calculated in this reference population are proposed as cut-off points for the definition of overweight and obesity in German children and adolescents

Measuring, in solution, multiple-fluorophore labeling by combining Fluorescence Correlation Spectroscopy and photobleaching

Determining the number of fluorescent entities that are coupled to a given molecule (DNA, protein, etc.) is a key point of numerous biological studies, especially those based on a single molecule approach. Reliable methods are important, in this context, not only to characterize the labeling process, but also to quantify interactions, for instance within molecular complexes. We combined Fluorescence Correlation Spectroscopy (FCS) and photobleaching experiments to measure the effective number of molecules and the molecular brightness as a function of the total fluorescence count rate on solutions of cDNA (containing a few percent of C bases labeled with Alexa Fluor 647). Here, photobleaching is used as a control parameter to vary the experimental outputs (brightness and number of molecules). Assuming a Poissonian distribution of the number of fluorescent labels per cDNA, the FCS-photobleaching data could be easily fit to yield the mean number of fluorescent labels per cDNA strand (@ 2). This number could not be determined solely on the basis of the cDNA brightness, because of both the statistical distribution of the number of fluorescent labels and their unknown brightness when incorporated in cDNA. The statistical distribution of the number of fluorophores labeling cDNA was confirmed by analyzing the photon count distribution (with the cumulant method), which showed clearly that the brightness of cDNA strands varies from one molecule to the other.Comment: 38 pages (avec les figures

Scoliosis and dental occlusion: a review of the literature

<p>Abstract</p> <p>Background</p> <p>Idiopathic scoliosis is a deformity without clear etiology. It is unclear wether there is an association between malocclusion and scoliosis. Several types of occlusion were described in subjects with scoliosis, mostly case-reports.</p> <p>Objectives</p> <p>The aim of this review was to evaluate the type of occluslins more prevalent in subjects with scoliosis</p> <p>Search strategy</p> <p>All randomised and controlled clinical trials identified from the Cochrane Oral Health Group Trials Register, a MEDLINE search using the Mesh term scoliosis, malocclusion, and relevant free text words, and the bibliographies of papers and review articles which reported the outcome of orthodontic treatment in subjects with scoliosis that were published as abstracts or papers between 1970 and 2010.</p> <p>Selection criteria</p> <p>All randomised and controlled clinical trials published as full papers or abstracts which reported quantitative data on the outcomes malocclusion in subjects with scoliosis.</p> <p>Data collection and analysis</p> <p>Data were extracted without blinding to the authors, age of patients or type of occlusion.</p> <p>Main results</p> <p>Using the search strategy eleven observational longitudinal studies were identified. No randomized clinical trials were recorded. Twenty-three cross-sectional studies were recorderd, and the others studies were reviews, editorials, case-reports, or opinions. The clinical trials were often not controlled and were about the cephalometric evaluation after treatment with the modified Milwuakee brace, followed by the orthodontic treatment of the class II relationship with a functional appliance. Clinical trials also included the study of the associations between scoliosis and unilateral crossbite, in children with asymmetry of the upper cervical spine. This association was also investigated in rats, pigs and rabbits in clinical trials. The other associations between scoliosis and occlusion seems to be based only on cross-sectional studies, case-reports, opinions.</p> <p>Authors' conclusions</p> <p>Based on selected studies, this review concludes that there is plausible evidence for an increased prevalence of unilateral Angle Class II malocclusions associated with scoliosis, and an increased risk of lateral crossbite, midline deviation in children affected by scoliosis. Also, documentation of associations between reduced range of lateral movements and scoliosis seem convincing. Data are also mentioned about the association between plagiocephaly and scoliosis.</p

The experimental power of FR900359 to study Gq-regulated biological processes.

Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism of action. We also use FR to investigate whether inhibition of Gq proteins is an effective post-receptor strategy to target oncogenic signalling, using melanoma as a model system. FR suppresses many of the hallmark features that are central to the malignancy of melanoma cells, thereby providing new opportunities for therapeutic intervention. Just as pertussis toxin is used extensively to probe and inhibit the signalling of Gi/o proteins, we anticipate that FR will at least be its equivalent for investigating the biological relevance of Gq