A Multilevel Meta‑Analysis

Insecure attachment to primary caregivers is associated with the development of depression symptoms in children and youth. This association has been shown by individual studies testing the relation between attachment and depression and by meta-analyses focusing on broad internalizing problems instead of depression or adult samples only. We therefore meta-analytically examined the associations between attachment security and depression in children and adolescents, using a multilevel approach. In total, 643 effect sizes were extracted from 123 independent samples. A significant moderate overall effect size was found (r = .31), indicating that insecure attachment to primary caregivers is associated with depression. Multivariate analysis of the significant moderators that impacted on the strength of the association between attachment security and depression showed that country of the study, study design, gender, the type of attachment, and the type of instrument to assess attachment uniquely contributed to the explanation of variance. This study suggests that insecure attachment may be a predictor of the development of depression in children and adolescents. When treating depression in children, attachment should therefore be addressed

α-Synuclein Radiotracer Development and In Vivo Imaging: Recent Advancements and New Perspectives

α-Synucleinopathies including idiopathic Parkinson's disease, dementia with Lewy bodies and multiple systems atrophy share overlapping symptoms and pathological hallmarks. Selective neurodegeneration and Lewy pathology are the main hallmarks of α-synucleinopathies. Currently, there is no imaging biomarker suitable for a definitive early diagnosis of α-synucleinopathies. Although dopaminergic deficits detected with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers can support clinical diagnosis by confirming the presence of dopaminergic neurodegeneration, dopaminergic imaging cannot visualize the preceding disease process, nor distinguish α-synucleinopathies from tauopathies with dopaminergic neurodegeneration, especially at early symptomatic disease stage when clinical presentation is often overlapping. Aggregated α-synuclein (αSyn) could be a suitable imaging biomarker in α-synucleinopathies, because αSyn aggregation and therefore, Lewy pathology is evidently an early driver of α-synucleinopathies pathogenesis. Additionally, several antibodies and small molecule compounds targeting aggregated αSyn are in development for therapy. However, there is no way to directly measure if or how much they lower the levels of aggregated αSyn in the brain. There is clearly a paramount diagnostic and therapeutic unmet medical need. To date, aggregated αSyn and Lewy pathology inclusion bodies cannot be assessed ante-mortem with SPECT or PET imaging because of the suboptimal binding characteristics and/or physicochemical properties of current radiotracers. The aim of this narrative review is to highlight the suitability of aggregated αSyn as an imaging biomarker in α-synucleinopathies, the current limitations with and lessons learned from αSyn radiotracer development, and finally to propose antibody-based ligands for imaging αSyn aggregates as a complementary tool rather than an alternative to small molecule ligands. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.</p

Work, life and time in the new economy: an introduction

International audienc

Rapid Low-Cost Microarray-Based Genotyping for Genetic Screening in Primary Immunodeficiency

Background: Genetic tests for primary immunodeficiency disorders (PIDs) are expensive, time-consuming, and not easily accessible in developing countries. Therefore, we studied the feasibility of a customized single nucleotide variant (SNV) microarray that we developed to detect disease-causing variants and copy number variation (CNV) in patients with PIDs for only 40 Euros. Methods: Probes were custom-designed to genotype 9,415 variants of 277 PID-related genes, and were added to the genome-wide Illumina Global Screening Array (GSA). Data analysis of GSA was performed using Illumina GenomeStudio 2.0, Biodiscovery Nexus 10.0, and R-3.4.4 software. Validation of genotype calling was performed by comparing the GSA with whole-genome sequencing (WGS) data of 56 non-PID controls. DNA samples of 95 clinically diagnosed PID patients, of which 60 patients (63%) had a genetically established diagnosis (by Next-Generation Sequencing (NGS) PID panels or Sanger sequencing), w

Instrumental-reasoned and symbolic-affective motives for using a motor car

This study was aimed at clarifying the relative importance of symbolic-affective as opposed to instrumental-reasoned motives for car use. We examined which motivational dimensions are underlying the (un)attractiveness of car use, in order to distinguish a limited set of main motive categories. Three methods were developed, which differed in the extent to which the purpose of the task was apparent. The tasks were: (1) a similarity sorting of car-use episodes, (2) a Q-sorting following attractiveness of car-use episodes, and (3) a semantic-differential method for evaluating (un)attractive aspects of car use. The symbolic-affective motives for car use were better expressed when the aim of the research task was not too apparent. If the aim of the task was evident, respondents tended to evaluate car use in terms of instrumental-reasoned motives. Overall, the results indicate that both instrumental-reasoned and symbolic-affective functions of the motor car are significant dimensions underlying the attractiveness of car use

Determination of <i>cis</i> vs <i>trans</i> orientation using next-generation sequencing (NGS).

<p>The Integrative Genomics Viewer (IGV) graphic report is from a patient with 2 adjacent variants on a single DNA molecule visualized with NGS on the MiSeq/QSAP platform. The <i>cis</i> orientation is clearly visible, as each strand contains either both or neither of the mutations.</p

Alignment of a 64 bp-deletion (41246533-41246596del; c.952_1015del) in a validation sample.

<p>The Integrative Genomics Viewer (IGV) graphic reports show detection of the deletion using MiSeq platform with QSAP (panel A) but not the PGM platform with Torrent Suite variant calling software (panel B).</p

Alignment of a 40-bp deletion in <i>BRCA1</i> (deletion c.1175_1214del40) in a validation sample.

<p>The Integrative Genomics Viewer (IGV) graphic report shows detection of the mutation with the PGM platform with Torrent Suite variant calling (panel A) but not the MiSeq platform with MiSeq Reporter (panel B). Use of QSAP with the MiSeq platform allowed detection of the deletion (panel C).</p

Schematic of the work flow for the next-generation sequencing (NGS) <i>BRCA1/ BRCA2</i> assay using both the MiSeq and the Personal Gene Machine (PGM) platforms.

<p>For the MiSeq platform, variant calling was performed initially with the vendor-supplied MiSeq Reporter software and then with the Quest Sequencing Analysis Pipeline (QSAP). For the PGM platform, the vendor-supplied Torrent Suite variant-calling software was used.</p