Cognitive-Behavioural Analysis System of Psychotherapy (CBASP), a drug, or their combination: differential therapeutics for persistent depressive disorder: a study protocol of an individual participant data network meta-analysis.

INTRODUCTION Despite important advances in psychological and pharmacological treatments of persistent depressive disorders in the past decades, their responses remain typically slow and poor, and differential responses among different modalities of treatments or their combinations are not well understood. Cognitive-Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy that has been specifically designed for chronic depression and has been examined in an increasing number of trials against medications, alone or in combination. When several treatment alternatives are available for a certain condition, network meta-analysis (NMA) provides a powerful tool to examine their relative efficacy by combining all direct and indirect comparisons. Individual participant data (IPD) meta-analysis enables exploration of impacts of individual characteristics that lead to a differentiated approach matching treatments to specific subgroups of patients. METHODS AND ANALYSIS We will search for all randomised controlled trials that compared CBASP, pharmacotherapy or their combination, in the treatment of patients with persistent depressive disorder, in Cochrane CENTRAL, PUBMED, SCOPUS and PsycINFO, supplemented by personal contacts. Individual participant data will be sought from the principal investigators of all the identified trials. Our primary outcomes are depression severity as measured on a continuous observer-rated scale for depression, and dropouts for any reason as a proxy measure of overall treatment acceptability. We will conduct a one-step IPD-NMA to compare CBASP, medications and their combinations, and also carry out a meta-regression to identify their prognostic factors and effect moderators. The model will be fitted in OpenBUGS, using vague priors for all location parameters. For the heterogeneity we will use a half-normal prior on the SD. ETHICS AND DISSEMINATION This study requires no ethical approval. We will publish the findings in a peer-reviewed journal. The study results will contribute to more finely differentiated therapeutics for patients suffering from this chronically disabling disorder. TRIAL REGISTRATION NUMBER CRD42016035886.

Characterization and age determination of Quaternary volcanism in the southern Ankaratra region (central Madagascar) through novel approaches in luminescence dating

This work introduces two novel approaches for the application of luminescence dating techniques to Quaternary volcanic eruptions: crystalline xenoliths from lava flows are demonstrated to be basically suitable for luminescence dating, and a set of phreatic explosion deposits from the Late Quaternary Vakinankaratra volcanic field in central Madagascar is successfully dated with infrared stimulated luminescence (IRSL). Using a numerical model approach and experimental verification, the potential for thermal resetting of luminescence signals of xenoliths in lava flows is demonstrated. As microdosimetry is an important aspect when using sample material extracted from crystalline whole rocks, autoradiography using image plates is introduced to the field of luminescence dating as a method for detection and assessment of spatially resolved radiation inhomogeneities. Determinations of fading rates of feldspar samples have been observed to result in aberrant g-values if the pause between preheat and measurement in the delayed measurements was kept short. A systematic investigation reveals that the phenomenon is caused by the presence of three signal components with differing individual fading behaviour. As this is restricted to short pauses, it is possible to determine a minimal required delay between preheating and measurement after which the aberrant behaviour disappears. This is applied in the measuring of 12 samples from phreatic explosion deposits from the Antsirabe – Betafo region in the Late Quaternary Vakinankaratra volcanic field. The samples were taken from stratigraphically correlatable sections and appear to represent at least three phreatic events, one of which created the Lac Andraikiba maar near Antsirabe. The obtained ages indicate that the eruptive activity in the region started in the Late Pleistocene between 113.9 and 99.6 ka. A second layer in the Betafo area is dated at approximately 73 ka and the Lac Andraikiba deposits give an age between 63.9 and 50.7 ka. The youngest phreatic layer is dated between 33.7 and 20.7 ka. These ages are the first recorded direct ages of such volcanic deposits, as well as the first and only direct ages for the Late Quaternary volcanism in the Vakinankaratra volcanic field. This illustrates the huge potential of this new method for volcanology and geochronology, as it enables direct numerical dating of a type of volcanic deposit which has not been successfully directly dated by any other method so far.