Psychopharmacology in children and adolescents: unmet needs and opportunities

Psychopharmacological treatment is an important component of the multimodal intervention approach to treating mental health conditions in children and adolescents. Currently, there are many unmet needs but also opportunities, alongside possible risks to consider, regarding the pharmacological treatment of mental health conditions in children and adolescents. In this Position Paper, we highlight and address these unmet needs and opportunities, including the perspectives of clinicians and researchers from the European College of Neuropsychopharmacology–Child and Adolescent Network, alongside those of experts by lived experience from national and international associations, via a survey involving 644 participants from 13 countries, and of regulators, through representation from the European Medicines Agency. We present and discuss the evidence base for medications currently used for mental disorders in children and adolescents, medications in the pipeline, opportunities in the development of novel medications, crucial priorities for the conduct of future clinical studies, challenges and opportunities in terms of the regulatory and legislative framework, and innovations in the way research is conducted, reported, and promoted

The flipflop orphan genes are required for limb bud eversion in the Tribolium embryo

Abstract Background Unlike Drosophila but similar to other arthropod and vertebrate embryos, the flour beetle Tribolium castaneum develops everted limb buds during embryogenesis. However, the molecular processes directing the evagination of epithelia are only poorly understood. Results Here we show that the newly discovered genes Tc-flipflop1 and Tc-flipflop2 are involved in regulating the directional budding of appendages. RNAi-knockdown of Tc-flipflop results in a variety of phenotypic traits. Most prominently, embryonic limb buds frequently grow inwards rather than out, leading to the development of inverted appendages inside the larval body. Moreover, affected embryos display dorsal closure defects. The Tc-flipflop genes are evolutionarily non-conserved, and their molecular function is not evident. We further found that Tc-RhoGEF2, a highly-conserved gene known to be involved in actomyosin-dependent cell movement and cell shape changes, shows a Tc-flipflop-like RNAi-phenotype. Conclusions The similarity of the inverted appendage phenotype in both the flipflop- and the RhoGEF2 RNAi gene knockdown led us to conclude that the Tc-flipflop orphan genes act in a Rho-dependent pathway that is essential for the early morphogenesis of polarised epithelial movements. Our work describes one of the few examples of an orphan gene playing a crucial role in an important developmental process

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking

Determination of the nonlinear optical susceptibility c(2) of surface layers by sum and difference frequency generation in reflection and transmission

The theor. investigation of sum and difference frequency generation in thin surface layers with rotational symmetry led to formulas which connected the generated light intensities to the surface 2nd-order nonlinear susceptibility tensor. A max. of 7 tensor components was detd. in the lowest symmetry case. Measurements in transmission were esp. useful since they allowed easy variation of both polarization and angle of incidence. Large signal enhancements are expected for total internal reflection geometries. A consistent set of c(2) tensor components for a thin layer of Rhodamine 6G adsorbed on fused SiO2 was found based on data from reflection and transmission measurements

Interactions between Light Waves in a Nonlinear Dielectric,” Phys.Rev. 127,

Quasi-phase-matching (QPM) is a method to get tailored efficient second order nonlinear interactions [5]. However, these electrodes were fabricated by wet etching and the sample thickness was limited to ~200 µm. In this work we present a new technique for 2D domain inversion in 1 mm thick RKTP and demonstrate the densest 2D lattice in a KTP isomorph. First, 2D periodic arrays of silicon pillars were constructed using isotropic dry etching ( . Second, the silicon arrays of pillars were used as contact electrode to periodically pole the RKTP crystal