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22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1‐weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source‐based morphometry (SBM) pipeline (SS‐Detect) to generate structural brain patterns (SBPs) that capture co‐varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV‐SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel‐based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism. [ABSTRACT FROM AUTHOR]

Background: In Australia, using non‐invasive prenatal testing (NIPT) to screen for fetal abnormalities is becoming more commonplace. However, there is a lack of standardised procedures surrounding pre‐test counselling. This holds the potential for variability in pregnant people's experiences when undergoing NIPT, which subsequently may impact their ability to make informed decisions surrounding NIPT results. Aim: This study sought to characterise the experiences of Australian women undergoing NIPT, including perceptions of informed choice, counselling experiences and decision to undergo NIPT. Materials and Methods: Australian women who had been recently pregnant (n = 94) completed an online survey which assessed: their knowledge of and attitude toward NIPT; satisfaction with counselling; satisfaction with their decision; and decisional conflict to undergo NIPT. The survey also allowed participants to provide qualitative information about their counselling experience and reasons for undergoing NIPT. Results: Overall, participants had good knowledge of and positive attitudes toward NIPT, experienced low decisional conflict and were overall satisfied with their counselling experience and decision to undergo NIPT. However, some participants expressed dissatisfaction with the lack of information provided, and biased language, by counselling providers. The desire to be informed was the most frequent reason for undergoing NIPT. Conclusion: The provision of accurate and objective information in pre‐test counselling is important to reduce decisional conflict and improve satisfaction with the decision to undergo NIPT. It is recommended counselling providers present pregnant people with neutral, objective, and accurate information at the time of pre‐test counselling. [ABSTRACT FROM AUTHOR]

Background: Early postnatal psychoeducation intervention programmes can support new parents in the adjustment to parenthood. However, most psychoeducation programmes focus on pregnancy and the birth and fail to deliver relevant and age‐specific information to new parents about what to expect in the postpartum period. Learning more about this intense period in a new parent's life will facilitate a healthy transition to parenthood. Considering the needs of time‐poor but tech‐savvy new parents, it is also necessary to rethink the delivery methods of such information to maximize impact. Method: Two panels of experts in perinatal mental health (eight professionals and eight parents with lived experience) participated in a Delphi consensus study to establish what topics of information are most important for parents in the first postnatal year. Results: A total of 89 topics of information were endorsed by at least 80% of both panels as Essential or Good to Know information for new parents. The topics were grouped under the following themes: sleep, attachment, co‐parenting, parental mental health, developmental milestones, feeding, social and community support, safety and health. Conclusions: This study established consensus between perinatal experts and parents with lived experience in order to produce relevant m‐health psychoeducation for parents in the first postnatal year. The study findings will inform the development of perinatal m‐health psychoeducation programmes. [ABSTRACT FROM AUTHOR]

Background: 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome. Parents of emerging adults with 22q11DS have an intense and ongoing involvement in their child's life. This study explores the lived experience of parents in relation to their child becoming independent and establishing intimate relationships. Method: Interpretative phenomenological analysis was used to explore the positive and negative experiences of five parents of emerging adults with 22q11DS. Results: Supervised independence overarched four subordinate themes. These themes highlighted the difficulties experienced by parents attempting to relinquish control whilst still experiencing a need to keep their child safe as their child negotiated a complex stage of life. Parents waited for "signs" from their child before initiating conversations about intimate relationships. Conclusions: These findings provide insight into the lived experience of parenting a child through the transition into adulthood, providing a catalyst for further research with the aim of facilitating better services for families. [ABSTRACT FROM AUTHOR]

Background/objectives Environmental exposure and personal susceptibility both contribute to the development of hand eczema. In this study, we investigated the effect of loss-of-function mutations in the filaggrin gene ( FLG), atopic dermatitis and wet work exposure on the development of hand eczema in apprentice nurses. Methods Dutch apprentice nurses were genotyped for the four most common FLG mutations; atopic dermatitis and hand eczema history were assessed by questionnaire. Exposure and hand eczema during traineeships were assessed with diary cards. Results The prevalence of hand eczema during traineeships was higher among subjects with a history of hand eczema reported at inclusion. Hand washing during traineeships and at home increased the risk of hand eczema. After adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5 (90% confidence interval 1.7-3.7) was found for a history of atopic dermatitis. In this study, an increased risk of hand eczema conferred by FLG mutations could not be shown, but subjects with concomitant FLG mutations and atopic dermatitis showed the highest risk of hand eczema during traineeships. Conclusion A history of atopic dermatitis, a history of hand eczema and wet work exposure were the most important factors increasing the risk of hand eczema during traineeships. [ABSTRACT FROM AUTHOR]

Feedforward inhibition deficits have been consistently demonstrated in a range of neuropsychiatric conditions using prepulse inhibition (PPI) of the acoustic startle eye-blink reflex when assessing sensorimotor gating. While PPI can be recorded in acutely decerebrated rats, behavioural, pharmacological and psychophysiological studies suggest the involvement of a complex neural network extending from brainstem nuclei to higher order cortical areas. The current functional magnetic resonance imaging study investigated the neural network underlying PPI and its association with electromyographically (EMG) recorded PPI of the acoustic startle eye-blink reflex in 16 healthy volunteers. A sparse imaging design was employed to model signal changes in blood oxygenation level-dependent (BOLD) responses to acoustic startle probes that were preceded by a prepulse at 120 ms or 480 ms stimulus onset asynchrony or without prepulse. Sensorimotor gating was EMG confirmed for the 120-ms prepulse condition, while startle responses in the 480-ms prepulse condition did not differ from startle alone. Multiple regression analysis of BOLD contrasts identified activation in pons, thalamus, caudate nuclei, left angular gyrus and bilaterally in anterior cingulate, associated with EMG-recorded sensorimotor gating. Planned contrasts confirmed increased pons activation for startle alone vs 120-ms prepulse condition, while increased anterior superior frontal gyrus activation was confirmed for the reverse contrast. Our findings are consistent with a primary pontine circuitry of sensorimotor gating that interconnects with inferior parietal, superior temporal, frontal and prefrontal cortices via thalamus and striatum. PPI processes in the prefrontal, frontal and superior temporal cortex were functionally distinct from sensorimotor gating. [ABSTRACT FROM AUTHOR]

The mammalian DYRK (dual specificity tyrosine phosphorylated and regulated kinase) family of protein kinases comprises a number of related, but poorly understood enzymes. DYRK1A is nuclear while DYRKs 2 and 3 are cytoplasmic. We recently showed that DYRK2 phosphorylates the translation initiation factor eIF2B at Ser539 in its ϵ-subunit and thereby 'primes' its phosphorylation by glycogen synthase kinase-3. Here we have used peptides based on the sequence around Ser539 to help define the specificity of DYRK2/3 in comparison with DYRK1A. These kinases require an arginine N-terminal to the target residue for efficient substrate phosphorylation. This cannot be replaced even by lysine. A peptide with arginine at −2 is phosphorylated much less well by all three kinases than one with arginine at −3. Replacement of the +1 proline by alanine almost completely eliminates substrate phosphorylation, but valine here does allow phosphorylation especially by DYRK2. This study reveals both similarities and differences in the specificities of these arginine-dependent protein kinases. [ABSTRACT FROM AUTHOR]

Eukaryotic initiation factor (elF) 2B is a heteromeric guanine nucleotide exchange factor that plays an important rote in regulating mRNA translation. Here we identify multiple phosphorylation sites in the largest, catalytic, subunit (∊) of mammalian eIF2B. These sites are phosphorylated by four different protein kinases. Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2B∊ with its substrate, eIF2, in vivo and for eIF2B activity in vitro. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2B∊ in vivo. The fifth site, which lies outside the catalytic domain of eIF2B∊, can be phosphorylated by casein kinase 1. All five sites are phosphorylated in the eIF2B complex in vivo. [ABSTRACT FROM AUTHOR]

In this article we review current mediation models for resolving custody and visitation disputes and their success rates and identify the characteristics of a subpopulation with poor outcome; those parents who are in high conflict, ambivalent about separation, emotionally distressed, and limited in their capacity to protect their children. Based on an understanding of what creates impasses, and how children are affected, we present a new model of mediation for this subpopulation. Preliminary outcome data using this model with 80 families is reported is reported. Implications for establishing a network of services for divorcing families are discussed. [ABSTRACT FROM AUTHOR]

Dense surface models can be used to analyze 3D facial morphology by establishing a correspondence of thousands of points across each 3D face image. The models provide dramatic visualizations of 3D face-shape variation with potential for training physicians to recognize the key components of particular syndromes. We demonstrate their use to visualize and recognize shape differences in a collection of 3D face images that includes 280 controls (2 weeks to 56 years of age), 90 individuals with Noonan syndrome (NS) (7 months to 56 years), and 60 individuals with velo-cardio-facial syndrome (VCFS; 3 to 17 years of age). Ten-fold cross-validation testing of discrimination between the three groups was carried out on unseen test examples using five pattern recognition algorithms (nearest mean, C5.0 decision trees, neural networks, logistic regression, and support vector machines). For discriminating between individuals with NS and controls, the best average sensitivity and specificity levels were 92 and 93% for children, 83 and 94% for adults, and 88 and 94% for the children and adults combined. For individuals with VCFS and controls, the best results were 83 and 92%. In a comparison of individuals with NS and individuals with VCFS, a correct identification rate of 95% was achieved for both syndromes. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html., (Copyright 2004 Wiley-Liss, Inc.)