Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

Von Netzalter, Wasserverlusten und Schadensraten zur langfristigen Erneuerungsplanung

Die Planung bzw. Festlegung einer langfristigen Erneuerungsstrategie für Trinkwasserversorgungsanlagen ist ein oft diskutiertes Thema und grundsätzlich keine einfache Aufgabe. So gibt es zum Beispiel auf der einen Seite die technische Nutzungsdauer von Trinkwasserrohrleitungen, die unter anderem von der Materialwahl, dem Durchmesser und den Untergrundverhältnissen abhängt, und auf der anderen Seite existieren betriebliche Zwänge, wie die gemeinsame Koordinierung von Baumaßnahmen mit anderen Leitungsträgern und/oder dem Straßenbau, die zu einer vorzeitigen Auswechslung von Rohrleitungen führen können. Für die Festlegung einer nachhaltigen und zufriedenstellenden Rehabilitationsplanung sollte der Zustand der Anlagen in Verbindung mit dem Rohrnetzalter genauer betrachtet werden. Für die Zustandsbewertung lassen sich beispielsweise die Wasserverluste und die vorhandenen Schadensraten heranziehen. Des Weiteren spielt die Siedlungsstruktur (z. B. ländlicher Bereich bzw. städtischer Bereich) hinsichtlich der Anlagenbelastungen eine wesentliche Rolle (z. B. Verkehrslasten, Grabungsaktivitäten) für die tatsächlichen Nutzungsdauern. Außerdem hat die Siedlungsstruktur entsprechende Auswirkungen auf die Rehabilitationskosten der Rohrleitungen. Im Beitrag wird dargestellt, wie bei der Rehabilitationsplanung die Zustandsbewertung der Anlagen einfließen kann. Welche Einflussfaktoren dabei zu beachten sind, wird anhand von aktuellen Erkenntnissen aus dem ÖVGW-Benchmarking hinsichtlich Netzalter, Wasserverluste und Schadensraten gezeigt. Anhand eines Beispiels der endgültigen Prioritätenreihung für die Erneuerungsplanung wird klar, dass auch die jeweilige Wichtigkeit eines Systemteils hinsichtlich der Versorgungssicherheit für die Planung eine Rolle spielt.Though planning/defining a long-term rehabilitation strategy for drinking-water supply facilities is a frequently discussed topic, it also represents a daunting challenge. Various factors have to be taken into account, e.g. the longevity of drinking-water distribution network which is determined by e.g. the choice of material, pipe diameter and underground conditions on the one hand; and by operational constraints e.g. the need to coordinate planned measures with other service providers and/or the road works, which can result in pipe sections being replaced sooner than planned on the other. In order to achieve sensible and sustainable rehabilitation planning, the current status of the facilities and distribution network must be carefully assessed. In this regard, aspects such as water loss and failure rates could be used as a basis for status appraisals. Furthermore, the municipal structure (e.g. urban or rural) significantly impacts the strain on facilities (e.g. through excavations, increased traffic, etc.), and accordingly, on their actual service lifespans. The specific distribution network structure also significantly impacts the cost of rehabilitation. The paper shows how the assessment of infrastructure current status can be used for better rehabilitation planning. On the basis of the latest insights gleaned from the ÖVGW benchmarking regarding network age, water loss and failure rates, it shows which influencing factors should be kept in mind. Finally, the example of a prioritization plan for rehabilitation strategy clearly demonstrates that the importance of a specific system component is also relevant for session making.(VLID)214133

Nosology of genetic skeletal disorders : 2023 revision

The "Nosology of genetic skeletal disorders" has undergone its 11th revision and now contains 771 entries associated with 552 genes reflecting advances in molecular delineation of new disorders thanks to advances in DNA sequencing technology. The most significant change as compared to previous versions is the adoption of the dyadic naming system, systematically associating a phenotypic entity with the gene it arises from. We consider this a significant step forward as dyadic naming is more informative and less prone to errors than the traditional use of list numberings and eponyms. Despite the adoption of dyadic naming, efforts have been made to maintain strong ties to the MIM catalog and its historical data. As with the previous versions, the list of disorders and genes in the Nosology may be useful in considering the differential diagnosis in the clinic, directing bioinformatic analysis of next-generation sequencing results, and providing a basis for novel advances in biology and medicine.Peer reviewe