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Heterogeneity of treatment outcomes across therapists and sites in a randomized multicentre psychotherapy trial
No full textObjectiveEstablishing robust evidence for psychotherapeutic treatment efficacy is crucial in evidence-based medicine for mental disorders. Randomized controlled trials (RCTs) are key to minimizing biases such as selection effects and baseline imbalances between study groups. However, another challenge to robust evidence in psychotherapy research is heterogeneity in treatment outcomes due to therapists and clinical sites. While this has been frequently observed in naturalistic settings, therapist- and site-related heterogeneity in treatment outcomes has been understudied in RCTs.MethodThe present study addresses this gap in a secondary data analysis, examining how therapists and clinical sites differ in treatment outcomes and differential/average treatment effect (i.e., outcome differences between treatment groups) within a large, multicentre RCT. We analysed data from 255 patients with chronic depression treated by 79 therapists in nine study sites, that received two different active psychotherapeutic interventions.ResultsTherapist- and site-related variances in treatment outcomes appeared relatively small, accounting for 1.1% [0.0%, 8.1%] and 1.7% [0.0%, 9.9%] of the total variance, respectively. Notably, site-related variance in differential treatment effects appeared relatively larger at 12.5% [0.1%, 44.4%]. These variances were only partially explained by patient or therapist characteristics.ConclusionWhile the sample size only allowed to estimate the variance contributions of therapists and sites with high uncertainty, the relative size comparison points to the importance of considering site heterogeneity in evaluating RCTs' differential treatment effects. Further research on site characteristics' impact could enhance understanding of psychotherapeutic treatment efficacy across diverse contexts
Metal fused filament fabrication (MF3) of Ti-6Al-4 V implants by using flexible, partially water-soluble binder systems
No full textMetal Fused Filament Fabrication provides a cost-efficient method to produce metal implants adapted to the patient. However, the limited flexibility of highly filled filaments and the reduced accuracy in comparison with alternative additive manufacturing techniques currently restrict the widespread implementation of this method. Building upon the findings of previous studies, the eco-friendly partially water-soluble binder systems containing polyethylene glycol (PEG), oly(vinylbutyral) (PVB) and poly(methylmethacrylat) (PMMA) were further optimized. Consequently, the influence of the plasticizer acetyltributylcitrate (ATBC) on the flow behavior and the flexibility of the filaments was investigated. The combination of all binder components, in conjunction with a solids content of 60 %, has enabled the fabrication of filaments with a high degree of usability, attributable to their remarkable flexibility and excellent printing properties. Following the debinding and sintering processes, the manufacturing of implants with densities that exceed 99.5 % of the theoretical values was feasible
TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors
No full textTFIID is an essential basal transcription factor, crucial for RNA polymerase II (pol II) promoter recognition and transcription initiation. The TFIID complex consists of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs) that contain intrinsically disordered regions (IDRs) with currently unknown functions. Here, we show that a conserved IDR drives TAF2 to nuclear speckle condensates independently of other TFIID subunits. Quantitative mass spectrometry analyses reveal TAF2 proximity to RNA splicing factors including specific interactions of the TAF2 IDR with SRRM2 in nuclear speckles. Deleting the IDR from TAF2 does not majorly impact global gene expression but results in changes of alternative splicing events. Further, genome-wide binding analyses suggest that the TAF2 IDR impedes TAF2 promoter association by guiding TAF2 to nuclear speckles. This study demonstrates that an IDR within the large multiprotein complex TFIID controls nuclear compartmentalization and thus links distinct molecular processes, namely transcription initiation and RNA splicing
Correction: Analysis of predefined safety events across spesolimab trials in dermatological and non-dermatological conditions
No full textLaserspektroskopische Analyse von CO2-Isotopologen : Entwicklung und Temperaturstabilisierung eines Gaszellenaufbaus
No full textThe size of critical secondary nuclei of polymer crystals does not depend on supersaturation
No full textIt is still a great challenge to determine the size of critical nuclei, which is crucial for a comprehensive understanding of crystallization and for testing the controversial crystallization theories. Here, we propose a method to determine the size of critical secondary nuclei on growth faces of poly(butylene succinate) single crystals in solution, basing on the probability of statistically selecting crystallizable units in random copolymers. In a dilute solution and for a given crystallization temperature, we reveal that the size of critical secondary nuclei was independent of supersaturation, contrary to the well-accepted prediction of existing theories which expect that the size of the critical nucleus increases with decreasing supersaturation. Accounting correctly for the dilution-caused change in the steady-state concentration of clusters of various sizes, we remedy inconsistencies of existing theoretical approaches in deriving the correct size of critical secondary nuclei in solution being independent of supersaturation