The Dimensional Assessment of Personality Pathology – Short Form for Adolescents (DAPP-SF-A): normative data for Flemish adolescents aged 16 to 21 years

Background:The Dimensional Assessment of Personality Pathology – Short Form for Adolescents (DAPP-SF-A) is an age-adapted version of the DAPP Basic Questionnaire (DAPP-BQ). The psychometric properties of this questionnaire were established by Tromp and Koot. However, norming data are currently available exclusively for Dutch adolescents.Objective:The main aim of this study was to provide community-based norming data for the DAPP-SF-A in Flemish adolescents and separately for boys and girls. The second aim was to compare the Flemish norms with the Dutch norms.Method:The sample consisted of 425 adolescents (52% girls), aged 16 to 21 years (mean, 18.6; SD, 1.16), from the general Flemish population. In 2012, all respondents completed the DAPP-SF-A and the Youth Self-Report as a part of the longitudinal Flemish Study on Parenting, Personality, and Development.Results:Internal consistency reliabilities of the lower-order dimensions were acceptable to good (a ranged from 0.71 to 0.87, median=0.85, mean item-rest correlations ranged from 0.44 to 0.67). The lower-order dimensions showed distinctive mean patterns for boys and girls, with higher scores for girls on Affective Instability and Insecure Attachment [effect sizes (d) were both −0.35] and higher scores for boys on all lower-order dimensions of Dissocial Behavior, Inhibitedness, and three lower-order dimensions of Emotional Dysregulation (d ranged from 0.21 to 0.79). The comparison of the Flemish scores with the Dutch scores showed substantial inter-cultural differences (d ranged from 0.13 to −1.78).Conclusions:The DAPP-SF-A shows satisfactory reliability in a Flemish community-based sample of adolescents. Furthermore, given the differences between boys and girls, the use of gender-based norms seems appropriate. Finally, substantial differences with the Dutch general population norms warrant the use of separate norms in Flemish adolescents

Aurora A, MCAK, and Kif18b promote Eg5-independent spindle formation

Inhibition of the microtubule (MT) motor protein Eg5 results in a mitotic arrest due to the formation of monopolar spindles, making Eg5 an attractive target for anti-cancer therapies. However, Eg5-independent pathways for bipolar spindle formation exist, which might promote resistance to treatment with Eg5 inhibitors. To identify essential components for Eg5-independent bipolar spindle formation, we performed a genome-wide siRNA screen in Eg5-independent cells (EICs). We find that the kinase Aurora A and two kinesins, MCAK and Kif18b, are essential for bipolar spindle assembly in EICs and in cells with reduced Eg5 activity. Aurora A promotes bipolar spindle assembly by phosphorylating Kif15, hereby promoting Kif15 localization to the spindle. In turn, MCAK and Kif18b promote bipolar spindle assembly by destabilizing the astral MTs. One attractive way to interpret our data is that, in the absence of MCAK and Kif18b, excessive astral MTs generate inward pushing forces on centrosomes at the cortex that inhibit centrosome separation. Together, these data suggest a novel function for astral MTs in force generation on spindle poles and how proteins involved in regulating microtubule length can contribute to bipolar spindle assembly

Silencing the Expression of Ras Family GTPase Homologues Decreases Inflammation and Joint Destruction in Experimental Arthritis

Changes in the expression and activation status of Ras proteins are thought to contribute to the pathological phenotype of stromal fibroblast-like synoviocytes (FLS) in rheumatoid arthritis, a prototypical immune-mediated inflammatory disease. Broad inhibition of Ras and related proteins has shown protective effects in animal models of arthritis, but each of the Ras family homologues (ie, H-, K-, and N-Ras) makes distinct contributions to cellular activation. We examined the expression of each Ras protein in synovial tissue and FLS obtained from patients with rheumatoid arthritis and other forms of inflammatory arthritis. Each Ras protein was expressed in synovial tissue and cultured FLS. Each homolog was also activated following FLS stimulation with tumor necrosis factor-α or interleukin (IL)-1β. Constitutively active mutants of each Ras protein enhanced IL-1β-induced FLS matrix metalloproteinase-3 production, while only active H-Ras enhanced IL-8 production. Gene silencing demonstrated that each Ras protein contributed to IL-1β-dependent IL-6 production, while H-Ras and N-Ras supported IL-1β-dependent matrix metalloproteinase-3 and IL-8 production, respectively. The overlap in contributions of Ras homologues to FLS activation suggests that broad targeting of Ras GTPases in vivo suppresses global inflammation and joint destruction in arthritis. Consistent with this, simultaneous silencing of H-Ras, K-Ras, and N-Ras expression significantly reduces inflammation and joint destruction in murine collagen-induced arthritis, while specific targeting of N-Ras alone is less effective in providing clinical benefits

The Gender-Diversity and Autism Questionnaire: A Community-Developed Clinical, Research, and Self-Advocacy Tool for Autistic Transgender and Gender-Diverse Young Adults

BACKGROUND: Autistic transgender people face unique risks in society, including inequities in accessing needed care and related mental health disparities. Given the need for specific and culturally responsive accommodations/supports, the characterization of key experiences, challenges, needs, and resilience factors within this population is imperative. This study developed a structured self-report tool for autistic transgender young adults to communicate their experiences and needs in a report format attuned to common autistic thinking and communication styles. METHODS: This cross-nation project developed and refined the Gender-Diversity and Autism Questionnaire through an iterative community-based approach using Delphi panel methodology. This proof-of-principle project defined expertise broadly, employing a multi-input expert search approach to balance academic-, community-, and lived experience-based expertise. RESULTS: The expert collaborators ( = 24 respondents) completed a two-round Delphi study, which developed 85 mostly closed-ended items based on 90% consensus. Final item content falls within six topic areas: and The majority of retained items relate to tasks and experiences of everyday life or the impact of experienced or anticipated discrimination, bias, and violence. CONCLUSIONS: This study employed a multipronged multimodal search approach to maximize equity in representation of the expert measure development team. The resulting instrument, designed for clinical, research, and self-advocacy applications, has parallel Dutch and English versions and is available for immediate use. Future cross-cultural research with this instrument could help identify contextual risk and resilience factors to better understand and address inequities faced by this large intersectional population