Generalisation of Social Communication Skills by Autistic Children During Play-Based Assessments Across Home, School and an Unfamiliar Research Setting

\ua9 The Author(s) 2024.We investigated autistic children’s generalisation of social communication over time across three settings during a play-based assessment with different adults and explore the potential moderating effects on generalisation of age, nonverbal IQ and level of restricted and repetitive behaviours. The social communication abilities of 248 autistic children (2–11 years, 21% female, 22% single parent, 60% white) from three UK sites were assessed from 1984 video interactions in three contexts with three different interaction partners (parent/home, teaching assistant/school, researcher/clinic) at baseline, midpoint (+ 7m) and endpoint (+ 12m) within the Paediatric Autism Communication Trial-Generalised (PACT-G), a parent-mediated social communication intervention. Children’s midpoint social communication at home generalised to school at midpoint and to clinic at endpoint. Generalisation was stronger from home to school and clinic than school to home and clinic. Generalisation was not moderated by age, nonverbal IQ or restricted and repetitive behaviour. Broader child development did not explain the pattern of results. The current study is the largest study to date to explore generalisation with autistic children and provides novel insight into their generalisation of social communication skills. Further research is needed to gain a more comprehensive understanding of facilitators of generalisation across settings and interaction partners in order to develop targeted strategies for interventions to enhance outcomes for young autistic children

Deep-Sequencing Analysis of the Mouse Transcriptome Response to Infection with Brucella melitensis Strains of Differing Virulence

Brucella melitensis is an important zoonotic pathogen that causes brucellosis, a disease that affects sheep, cattle and occasionally humans. B. melitensis strain M5-90, a live attenuated vaccine cultured from B. melitensis strain M28, has been used as an effective tool in the control of brucellosis in goats and sheep in China. However, the molecular changes leading to attenuated virulence and pathogenicity in B. melitensis remain poorly understood. In this study we employed the Illumina Genome Analyzer platform to perform genome-wide digital gene expression (DGE) analysis of mouse peritoneal macrophage responses to B. melitensis infection. Many parallel changes in gene expression profiles were observed in M28- and M5-90-infected macrophages, suggesting that they employ similar survival strategies, notably the induction of anti-inflammatory and antiapoptotic factors. Moreover, 1019 differentially expressed macrophage transcripts were identified 4 h after infection with the different B. melitensis strains, and these differential transcripts notably identified genes involved in the lysosome and mitogen-activated protein kinase (MAPK) pathways. Further analysis employed gene ontology (GO) analysis: high-enrichment GOs identified endocytosis, inflammatory, apoptosis, and transport pathways. Path-Net and Signal-Net analysis highlighted the MAPK pathway as the key regulatory pathway. Moreover, the key differentially expressed genes of the significant pathways were apoptosis-related. These findings demonstrate previously unrecognized changes in gene transcription that are associated with B. melitensis infection of macrophages, and the central signaling pathways identified here merit further investigation. Our data provide new insights into the molecular attenuation mechanism of strain M5-90 and will facilitate the generation of new attenuated vaccine strains with enhanced efficacy

The cultural, family and community factors for resilience in Southeast Asian indigenous communities: a systematic review

Although faced with historical and ongoing hardships, many indigenous communities in Southeast Asia have managed to survive and thrive. The identification of factors that assist these communities in coping with the challenges experienced would help enhance their overall psychological well‐being and resilience. The current review outlines types of protective factors for the indigenous communities in Southeast Asia focusing on the cultural, family and community elements linked to their psychological well‐being. Four themes of protective factors were identified strong connection to the land and the environment, embracing cultural norms and traditions, passing down and keeping indigenous knowledge across generations, and emphasis on community and social cohesion. Findings suggest that the value of interconnectedness serves as an overarching theme that forms the worldview of the indigenous communities in Southeast Asia. Interconnectedness was important to the indigenous peoples as they considered themselves to be extensions of their family, community, ancestors, future descendants, the land and to all living things and creations that reside on their lands. Future intervention attempts to promote resilience among these communities should take these factors into account, and pay closer attention to community‐level factors that seem to have a profound impact on the indigenous construction of resilience

Postpartum psychiatric disorders

Pregnancy is a complex and vulnerable period that presents a number of challenges to women, including the development of postpartum psychiatric disorders (PPDs). These disorders can include postpartum depression and anxiety, which are relatively common, and the rare but more severe postpartum psychosis. In addition, other PPDs can include obsessive–compulsive disorder, post-traumatic stress disorder and eating disorders. The aetiology of PPDs is a complex interaction of psychological, social and biological factors, in addition to genetic and environmental factors. The goals of treating postpartum mental illness are reducing maternal symptoms and supporting maternal–child and family functioning. Women and their families should receive psychoeducation about the illness, including evidence-based discussions about the risks and benefits of each treatment option. Developing effective strategies in global settings that allow the delivery of targeted therapies to women with different clinical phenotypes and severities of PPDs is essential

Dosing algorithms for vitamin K antagonists across VKORC1 and CYP2C9 genotypes

BACKGROUND: The multicenter, single-blind, randomized EU-PACT trial compared safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep venous thrombosis. The trial showed no differences in the primary outcome between the two dosing strategies. OBJECTIVES: To explore possible reasons for the lack of differences between trial arms this secondary analysis of EU-PACT data evaluated the performance of both dosing algorithms across VKORC1-CYP2C9 genetic sub-groups. PATIENTS/METHODS: Anticoagulation control measured by international normalized ratio (INR) below (INR3) the therapeutic range was compared across VKORC1-CYP2C9 sub-groups. Due to a low number of patients per sub-group, trials for acenocoumarol and phenprocoumon were combined for analysis. RESULTS: Four weeks after therapy initiation genotype-guided dosing increased the mean percentage of time in therapeutic INR range (PTIR) in the VKORC1 GG-CYP2C9 *1*1 sub-group as compared to the non-genetic dosing (%-point difference 14.68, 95% CI [5.38; 23.98]). For the VKORC1 AA-CYP2C9 *1*1 sub-group, there was a higher risk of under-anticoagulation with the genotype-guided algorithm (19.9%-points; 95% CI, 11.6 to 28.2). Twelve weeks after therapy initiation no statistically significant differences in anticoagulation control between trial arms were noted across the VKORC1-CYP2C9 genetic sub-groups. CONCLUSIONS: EU-PACT genetic-guided dose initiation algorithms for acenocoumarol and phenprocoumon could have predicted the dose extra cautiously in the VKORC1 AA-CYP2C9 *1*1 sub-group. Adjustment of the genotype-guided algorithm could lead to a higher benefit of genotyping. This article is protected by copyright. All rights reserved

The Concept of Stability in the Context of Conventional War in Europe

`Stability' is a widely used concept in strategic analysis, especially in the context of nuclear strategy. This article examines the meaning of the term, and shows how it can be usefully applied to problems of conventional war, especially as these problems apply to Europe. In scientific usage, stability is the condition in which a slight disturbance in a system does not produce too disturbing an effect on that system. Traditionally, military writings in both East and West have been more deeply concerned with balance than with stability. In Europe today there is a paradox of strategic stability: the danger of instability at high levels of conflict promotes stability at low levels. Nevertheless, there are many political problems in Europe that are potential causes of instability and that should not be ignored. Attending to the problems of strategic stability also means a concern with linkages between conventional and nuclear war, vulnerabilities of armies to surprise attacks, maintenance of command and control, the relative strength of the defense compared to the offense, and the subtle interacting effects of dispersal, alert, and mobilization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68323/2/10.1177_0022343390027003002.pd