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Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study.
Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling.
Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders).
Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
Für die Steinartefakte der ältesten Linearbandkeramik (LBK) liegen bisher kaum mikrofossile oder chemische Analysen zur Herkunftsbestimmung der Rohmaterialien vor, was das Bild der Rohmaterialversorgung auf einem sehr allgemeinen Niveau hält. Es werden die Rohmaterialanalysen des Inventars Langenbach-Niederhummel, Lkr. Freising, Obb., vorgestellt und mit dem bisherigen Forschungsstand diskutiert. Es zeigt sich die intensive Anbindung an das Revier des Ortenburger Raumes, was die Bedeutung der Isar als Verbindungsweg unterstreicht. Aufgrund der technologischen Analyse des Inventars ist von einer Produktion innerhalb der Siedlung auszugehen, was auf eine Selbstversorgung der Siedlung schließen lässt. Dies betont, dass sich die Siedlung in einer eher isolierten Position befand und es noch kein etabliertes Weitergabenetzwerk für Austauschprozesse gab. Mehrere Rohmaterialtypen weisen über das Verbreitungsgebiet der ältesten Linearbandkeramik hinaus. Vor allem die angezeigten transalpinen Verbindungen lassen sich durch weitere Beispiele in einen räumlichen und zeitlichen Kontext setzen. Die Ergebnisse bestätigen eine Kontinuität dieser Routen seit dem Mesolithikum, die sich nach der Linearbandkeramik auch in späteren neolithischen Phasen abzeichnen. Vor dem Hintergrund dieser Ergebnisse stellt sich die Frage nach dem Mobilitätsfaktor, der ursächlich für solche Rohmaterialbezüge ist.
Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.