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Background: The aim of this study was to develop a child-specific classification system for long bone fractures and to examine its reliability and validity on the basis of a prospective multicentre study. Methods: Using the sequentially developed classification system, three samples of between 30 and 185 paediatric limb fractures from a pool of 2308 fractures documented in two multicenter studies were analysed in a blinded fashion by eight orthopaedic surgeons, on a total of 5 occasions. Intra- and interobserver reliability and accuracy were calculated. Results: The reliability improved with successive simplification of the classification. The final version resulted in an overall interobserver agreement of kappa=0.71 with no significant difference between experienced and less experienced raters. Conclusions: In conclusion, the evaluation of the newly proposed classification system resulted in a reliable and routinely applicable system, for which training in its proper use may further improve the reliability. It can be recommended as a useful tool for clinical practice and offers the option for developing treatment recommendations and outcome predictions in the future.
In den letzten Jahren ist die Weltöffentlichkeit Zeuge vieler sozialer Proteste und auch einiger neuen Protestformen geworden: Sei es die revoltierende Jugend im sogenannten Arabischen Frühling, die Indignados in Spanien, die 99% der Occupy-Bewegung oder lokale Proteste gegen Staudammprojekte im Amazonas und Stadtentwicklungspolitik in Berlin und Hamburg - überall versammeln und organisieren sich in zunehmendem Maße Menschen, um gemeinsam zu protestieren und Widerstand zu leisten. Der gemeinsame Nenner all dieser spezifisch doch recht unterschiedlichen Bewegungen ist, dass sie durch die neuen Kommunikationstechnologien ganz neue Formen des kollektiven Protests hervorgebracht haben.
In den Weblogs der Zeit hat sich in den letzten zwei Wochen eine interessante, weil emotionale und problematische Debatte über Verständnis und Unverständnis terroristischer Gewalt entwickelt. Die Debatte ist emotional, da der Ausgangspost von Jörg Lau, persönlich betroffen, ja gar aufgewühlt daher kommt und bisher 1314 Kommentare provoziert hat. Die von Lau und Yassin Musharbash in seiner Replik vertretenen Thesen sind problematisch, da sie unzulässig verkürzen. Die Debatte ist interessant, da sie uns einen Blick auf den Umgang mit terroristischer Gewalt vor allem in Journalismus und Wissenschaft, aber auch in der Gesellschaft erlaubt...
The bile acid activated transcription factor farnesoid X receptor (FXR) regulates numerous metabolic processes and is a rising target for the treatment of hepatic and metabolic disorders. FXR agonists have revealed efficacy in treating non-alcoholic steatohepatitis (NASH), diabetes and dyslipidemia. Here we characterize imatinib as first-in-class allosteric FXR modulator and report the development of an optimized descendant that markedly promotes agonist induced FXR activation in a reporter gene assay and FXR target gene expression in HepG2 cells. Differential effects of imatinib on agonist-induced bile salt export protein and small heterodimer partner expression suggest that allosteric FXR modulation could open a new avenue to gene-selective FXR modulators.
With every glimpse of our eyes, we sample only a small and incomplete fragment of the visual world, which needs to be contextualized and integrated into a coherent scene representation. Here we show that the visual system achieves this contextualization by exploiting spatial schemata, that is our knowledge about the composition of natural scenes. We measured fMRI and EEG responses to incomplete scene fragments and used representational similarity analysis to reconstruct their cortical representations in space and time. We observed a sorting of representations according to the fragments' place within the scene schema, which occurred during perceptual analysis in the occipital place area and within the first 200 ms of vision. This schema-based coding operates flexibly across visual features (as measured by a deep neural network model) and different types of environments (indoor and outdoor scenes). This flexibility highlights the mechanism's ability to efficiently organize incoming information under dynamic real-world conditions.
Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development.
The nuclear farnesoid X receptor (FXR) and the enzyme soluble epoxide hydrolase (sEH) are validated molecular targets to treat metabolic disorders such as non‐alcoholic steatohepatitis (NASH). Their simultaneous modulation in vivo has demonstrated a triad of anti‐NASH effects and thus may generate synergistic efficacy. Here we report dual FXR activators/sEH inhibitors derived from the anti‐asthma drug Zafirlukast. Systematic structural optimization of the scaffold has produced favorable dual potency on FXR and sEH while depleting the original cysteinyl leukotriene receptor antagonism of the lead drug. The resulting polypharmacological activity profile holds promise in the treatment of liver‐related metabolic diseases.
Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.
Non-alcoholic steatohepatitis (NASH) - a hepatic manifestation of the metabolic syndrome - is a multifactorial disease with alarming global prevalence. It involves steatosis, inflammation and fibrosis in the liver, thus demanding multiple modes of action for robust therapeutic efficacy. Aiming to fuse complementary validated anti-NASH strategies in a single molecule, we have designed and systematically optimized a scaffold for triple activation of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor (PPAR) α and PPARδ. Pilot profiling of the resulting triple modulator demonstrated target engagement in native cellular settings and in mice, rendering it a suitable tool to probe the triple modulator concept in vivo. In DIO NASH in mice, the triple agonist counteracted hepatic inflammation and reversed hepatic fibrosis highlighting the potential of designed polypharmacology in NASH.