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Craniosynostosis, defined by premature fusion of one or multiple cranial sutures, is a common congenital defect affecting more than 1/2000 infants and results in restricted brain expansion. Single gene mutations account for 15%-20% of cases, largely as part of a syndrome, but the majority are nonsyndromic with complex underlying genetics. We hypothesized that the two noncoding genomic regions identified by a GWAS for craniosynostosis contain distal regulatory elements for the risk genes BMPER and BMP2. To identify such regulatory elements, we surveyed conserved noncoding sequences from both risk loci for enhancer activity in transgenic Danio rerio. We identified enhancers from both regions that direct expression to skeletal tissues, consistent with the endogenous expression of bmper and bmp2. For each locus, we also found a skeletal enhancer that also contains a sequence variant associated with craniosynostosis risk. We examined the activity of each enhancer during craniofacial development and found that the BMPER-associated enhancer is active in the restricted region of cartilage closely associated with frontal bone initiation. The same enhancer is active in mouse skeletal tissues, demonstrating evolutionarily conserved activity. Using enhanced yeast one-hybrid assays, we identified transcription factors that bind each enhancer and observed differential binding between alleles, implicating multiple signaling pathways. Our findings help unveil the genetic mechanism of the two craniosynostosis risk loci. More broadly, our combined in vivo approach is applicable to many complex genetic diseases to build a link between association studies and specific genetic mechanisms.

The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

When children are killed or seriously harmed from abuse or neglect, there is pressure to 'learn the lessons' to prevent similar events. England has a long-established system of locally-based multi-agency reviews for this, but the recurrence of tragedies and repetitive findings raise questions about its effectiveness. Reflecting and building on our research into reviews completed between 2017 and 2021, we analyse the complexity that routine criticisms of inter-agency working disguise, and argue that reviews are shaped by their multiple, competing functions. The stated purpose is to improve practice. Within this are other overt but ambiguous goals: establishing what happened, accountability, reassurance and commemoration. Then there are covert functions: to dissipate public outrage, deflect attention from underlying causes, and distort understandings of the work by making it seem straightforward. Reviews would benefit from paying more attention to the dynamics of frontline practice and the local actions to implement the lessons. [ABSTRACT FROM AUTHOR]

This article offers a new conceptualisation of sensemaking in social work assessment. During assessment, social workers are required to make sense of a wide range of information. This may include written reports, behavioural cues, verbal, sensory and emotional data. In this article, the term "sensemaking" is used to refer to the processes through which social workers gather, select and interpret this varied, and often incomplete, information during assessment. Sensemaking is defined as a psychosocial process which precedes and underpins professional judgement and decision-making. While there has been interest in how social workers assess risk to children, the sensemaking process that occurs before a decision is made has received less attention, and sensemaking lacks a clear definition. Drawing on existing research on assessment and theoretical literature from the fields of psychology and organisational studies, this article offers a view of sensemaking through three lenses: sensemaking as intuitive process, sensemaking as social storytelling and sensemaking as an emotionally-informed process. Drawing together key features from these three perspectives, we advance six propositions about sensemaking in child and family assessment: (1) sensemaking is a process of formulation; (2) sensemaking involves movement between conscious and non-conscious processes; (3) sensemaking can be developed through experience and learning through reflection; (4) sensemaking is inseparable from the environment in which it takes place (5) sensemaking is a dialogic process; (6) sensemaking is an emotionally-informed as well as cognitive process. The article concludes with the implications of this conceptualisation of sensemaking for assessment in child and family social work.

Introduction: Pediatric integrated care is well-positioned to play a substantial role in crisis intervention; however, few studies have investigated the impact of these services. Method: We investigated differences in service utilization for youth experiencing a crisis in a large, predominantly rural health system by comparing outcomes for 171 youth who received a crisis evaluation in a primary care behavioral health (PCBH) setting to 171 youth presenting to the emergency department at the main hospital campus using a retrospective cohort study design. Results: PCBH patients were less likely to be male, more likely to be diagnosed with an Adjustment Disorder and less likely to be diagnosed with Autism Spectrum Disorder. Youth evaluated in PCBH were more likely to receive a psychiatric admission, had a shorter latency to the next BH appointment, and had higher rates of completing at least 1 visit in the year following the evaluation. A statistically nonsignificant reduction in frequency of psychiatric admission was observed in the year after the index date, with 3 integrated care patients (vs. 18 on index date) and 5 ED patients (vs. 6 on index date) admitted. Discussion: Opportunities for future research on cost-effectiveness of care and continuous improvement aligned with quadruple aim outcomes are discussed. Overall, this study is among few others investigating the potential for pediatric integrated care models to contribute to youth suicide prevention and the study demonstrated promising increases in access and engagement with timely behavioral health care. Keywords: integrated care, crisis evaluation, adolescents, behavioral health, A crisis is defined as 'a situation (e.g., a traumatic change) that produces significant cognitive or emotional stress in those involved in it' (VandenBos, 2007). Youth at-risk for suicide are [...]

Despite a history of critique, concentrated discussion and improved assessment processes, neglect continues to be a major challenge for child protection services. This paper draws on findings from a government‐commissioned analysis of 'serious case reviews' (SCRs) in England, arising from incidents of serious child abuse in 2017–2019. There were 235 cases, for which 166 final reports were available. Alongside a quantitative analysis of the whole cohort, we undertook an in‐depth qualitative analysis of 12 cases involving neglect. A key challenge in responding to neglect in its different forms is that it can be so widespread amongst families that practitioners no longer notice its severity or chronicity – it becomes normalised. In this paper we explore two dimensions of the 'paradox of neglect' where it seems to be everywhere and nowhere simultaneously. The first is that neglect is so closely bound up with the prevalence of poverty that little action is taken to address it. The second is that the overwhelming nature of neglect can blind practitioners to other forms of maltreatment that may also be present within a family. Practitioners, now more than ever, need to recognise the dimensions of this paradox to protect children from neglect. [ABSTRACT FROM AUTHOR]