The relevance of schizotypal traits for understanding interpersonal functioning in adolescents with psychiatric problems.

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Cross-Lingual Knowledge Transfer for Clinical Phenotyping

Clinical phenotyping enables the automatic extraction of clinical conditions from patient records, which can be beneficial to doctors and clinics worldwide. However, current state-of-the-art models are mostly applicable to clinical notes written in English. We therefore investigate cross-lingual knowledge transfer strategies to execute this task for clinics that do not use the English language and have a small amount of in-domain data available. We evaluate these strategies for a Greek and a Spanish clinic leveraging clinical notes from different clinical domains such as cardiology, oncology and the ICU. Our results reveal two strategies that outperform the state-of-the-art: Translation-based methods in combination with domain-specific encoders and cross-lingual encoders plus adapters. We find that these strategies perform especially well for classifying rare phenotypes and we advise on which method to prefer in which situation. Our results show that using multilingual data overall improves clinical phenotyping models and can compensate for data sparseness.Comment: LREC 2022 submmision: January 202

Understanding personality pathology in a clinical sample of youth: study protocol for the longitudinal research project 'APOLO'

Introduction We propose that a dimensional, multilayered perspective is well suited to study maladaptive personality development in youth. Such a perspective can help understand pathways to personality pathology and contribute to its early detection. The research project 'APOLO' (a Dutch language acronym for Adolescents and their Personality Development: a Longitudinal Study) is designed based on McAdams' integrative three-layered model of personality development and assesses the interaction between dispositional traits, characteristic adaptations, the narrative identity and functioning. Methods and analysis APOLO is a longitudinal research project that takes place in two outpatient mental healthcare centres. Participants are youth between 12 years and 23 years and their parents. Data collection is set up to build a data set for scientific research, as well as to use the data for diagnostic assessment and systematic treatment evaluation of individual patients. Measurements are conducted half-yearly for a period of 3 years and consist of self-report and informant-report questionnaires and a semistructured interview. The included constructs fit the dimensional model of personality development: maladaptive personality traits (dispositional traits), social relations, stressful life events (characteristic adaptations), a turning point (narrative identity) and functioning (eg, achievement of youth specific milestones). Primary research questions will be analysed using structural equation modelling. Ethics and dissemination The results will contribute to our understanding of (the development of) personality pathology as a complex phenomenon in which both structural personality characteristics as well as unique individual adaptations and experiences play a role. Furthermore, results will give directions for early detection and timely interventions. This study has been approved by the ethical review committee of the Utrecht University Faculty for Social and Behavioural Sciences (FETC17-092). Data distribution will be anonymous and results will be disseminated via communication canals appropriate for diverse audiences. This includes both clinical and scientific conferences, papers published in national and international peer-reviewed journals and (social) media platforms

Титульные страницы и содержание

This study gives an overview of Project STARS (Studies on Trajectories of Adolescent Relationships and Sexuality), a four-wave longitudinal study of 1297 Dutch adolescents. First, the sample, measures and four sub-projects are described. Second, hierarchical regression analyses were conducted to examine how key variables from the individual domain (impulsivity), parent domain (parent-adolescent relationship quality), peer domain (involvement with peers) and media domain (time spent on social networking sites), and their interactions predict changes in the experience with sexual behaviour of adolescents across time. Results showed that higher levels of impulsivity, lower quality of relation with parents, more frequent involvement with peers and more time spent on social networking sites at baseline predicted increases in sexual experience of adolescents over a subsequent 1.5-year time period. No interaction effects among the domains were found. The findings highlight the significance of a multi-domain approach to the study of adolescent sexual development

The Lectin-like Domain of Thrombomodulin Confers Protection from Neutrophil-mediated Tissue Damage by Suppressing Adhesion Molecule Expression via Nuclear Factor κB and Mitogen-activated Protein Kinase Pathways

Thrombomodulin (TM) is a vascular endothelial cell (EC) receptor that is a cofactor for thrombin-mediated activation of the anticoagulant protein C. The extracellular NH2-terminal domain of TM has homology to C-type lectins that are involved in immune regulation. Using transgenic mice that lack this structure (TMLeD/LeD), we show that the lectin-like domain of TM interferes with polymorphonuclear leukocyte (PMN) adhesion to ECs by intercellular adhesion molecule 1–dependent and –independent pathways through the suppression of extracellular signal–regulated kinase (ERK)1/2 activation. TMLeD/LeD mice have reduced survival after endotoxin exposure, accumulate more PMNs in their lungs, and develop larger infarcts after myocardial ischemia/reperfusion. The recombinant lectin-like domain of TM suppresses PMN adhesion to ECs, diminishes cytokine-induced increase in nuclear factor κB and activation of ERK1/2, and rescues ECs from serum starvation, findings that may explain why plasma levels of soluble TM are inversely correlated with cardiovascular disease. These data suggest that TM has antiinflammatory properties in addition to its role in coagulation and fibrinolysis

Experimental and theoretical aspects of internal friction associated with the melting of embedded particles

Internal friction associated with the volume change during melting was studied in an aluminum-16 wt% indium alloy. This alloy was processed to obtain microstructures consisting of nominally pure indium inclusions embedded in an aluminum matrix. Two sharp internal friction peaks were observed near the indium melting temperature of 156[deg]C and both were associated with the formation and growth of liquid nuclei. A general theoretical model for the internal friction was developed which incorporates both the rates of phase deformation and the relaxation of the surrounding matrix. The proposed model considers the effect of the hydrostatic stress generated during melting that initially opposes the transformation. Matrix relaxation around the transforming particles resulting from vacancy flux and dislocation climb contributes an additional frequency dependence to the internal friction. Both the matrix relaxation and the internal friction peak height were found to be dependent upon thermomechanical processing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30827/1/0000489.pd

Surface plasmon modes of a single silver nanorod: an electron energy loss study

We present an electron energy loss study using energy filtered TEM of spatially resolved surface plasmon excitations on a silver nanorod of aspect ratio 14.2 resting on a 30 nm thick silicon nitride membrane. Our results show that the excitation is quantized as resonant modes whose intensity maxima vary along the nanorod's length and whose wavelength becomes compressed towards the ends of the nanorod. Theoretical calculations modelling the surface plasmon response of the silver nanorod-silicon nitride system show the importance of including retardation and substrate effects in order to describe accurately the energy dispersion of the resonant modes.Comment: 9 pages, 6 figure

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies

Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes

Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae. Hominidae show between four- and sevenfold lower rates of nucleotide change and feature turnover in both neutral and functional sequences, suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. Recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli, which resulted in thousands of novel, species-specific CTCF binding sites. Our results show that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology