‘Intensive mothering’ in the early years: the cultivation and consolidation of (physical) capital

Growing pressure on parents to equip their children with the skills required for future success, coupled with an increased focus on providing quality learning experiences in the early years, has contributed to an upsurge in the enrolment of young children in formal (often privatised) activities. Moreover, in response to growing societal concerns over the perceived risks of obesity and sedentary lifestyles, parents are often acutely aware of the importance of providing plentiful physical activity opportunities for their children within this enrichment context. In this paper, the tendency for parents to provide copious developmental opportunities is referred to as ‘intensive mothering’ and is explored through the theoretical lens of Bourdieu, specifically his concepts of habitus and capital. This paper reports on a small-scale study undertaken within the UK, which sought to explore the impact of social class on access to early years’ provision as well as parental attitudes towards physical activity and the provision of preschool physical development opportunities. Data were generated through a questionnaire (disseminated via early years settings) as well as three in-depth interviews with ‘middle-class’ parents and were analysed to draw out key themes relating to the cultivation and consolidation of (physical) capital. The data indicate that many parents perceive a ‘responsibility’ to aid their children's physical development and demonstrate a willingness to facilitate the acquisition of physical capital via the provision of play equipment, privatised classes and additional (informal) physical activity opportunities. Moreover, they suggest that ‘middle-class’ parents, in particular, articulate the need to invest heavily in enrichment activities, influenced by their own experiences, tastes and values. It is argued that ‘intensive mothering’ is illustrative of the reproduction of a class-based habitus and can be perceived as an attempt to maintain or improve social position through the cultivation, consolidation and, ultimately, conversion, of appropriate capital

The role of physical activity/sport in tackling youth disaffection and anti-social behaviour

The purpose of this paper is to examine the existing evidence about the impact of sport/physical activity programmes on positive youth development in the context of education. The issue of youth disaffection is topical and a number of authors and policy makers have acknowledged that physical activity/sport may be an effective way of helping to address the problem. As a result, a number of initiatives aimed at re‐engaging disaffected or disadvantaged young people through physical activities have been developed and implemented in schools in the UK. Two such initiatives, the HSBC/Outward Bound project and Youth Sport Trust/BSkyB ‘Living For Sport’ programme, are discussed within this paper, and key findings from the monitoring and evaluation of each initiative are presented. Over a period of three years, more than 7000 pupils have been engaged in these programmes, and complete data sets have been collated for over 50% and 90% of Sky Living For Sport and HSBC/Outward Bound participants respectively. The findings suggest that both of these projects have had a positive impact on the behaviour and attendance of large numbers of pupils, and that engagement in lessons and relationships with both teachers and peers have improved and can be sustained. The findings also demonstrate, however, that impact is highly individualised and context‐specific in many cases, and that positive impact is more likely to be sustained when some or all of the following project features are in place: effective matching of pupil needs with the specific project objectives; locating project activities outside of the ‘normal’ school context; working closely with pupils to choose activities, set targets and review progress; establishing positive relationships between project leaders/supporters (mentors) and pupils; and giving pupils the opportunity to work with and for others

Ability to be active: exploring children’s active play in primary schools

This paper presents findings from an innovative multi-method study which sought to examine the impact of toys and toy substitutes on children’s physical activity levels in two UK primary schools. Accelerometers were used to record the physical activity levels of 52 Year 3 pupils (aged 7-8 years) during four separate 30-minute play sessions and, for comparison, during other periods of the school day (breaks, lunch-times and PE lessons). Qualitative data were generated through observations, field notes and semi-structured focus groups with pupils. The findings suggest that a relatively short session of unstructured active play with toys or toy substitutes can make an important contribution to a child’s daily level of physical activity. Moreover, they reveal that children’s enjoyment of play sessions and their creative, physical and social competence are also important influences on their engagement in, and with active, play. Some implications for policy, practice and future research are discussed

Amino acid residues in five separate HLA genes can explain most of the known associations between the MHC and primary biliary cholangitis.

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterised by progressive destruction of intrahepatic bile ducts. The strongest genetic association is with HLA-DQA1*04:01, but at least three additional independent HLA haplotypes contribute to susceptibility. We used dense single nucleotide polymorphism (SNP) data in 2861 PBC cases and 8514 controls to impute classical HLA alleles and amino acid polymorphisms using state-of-the-art methodologies. We then demonstrated through stepwise regression that association in the HLA region can be largely explained by variation at five separate amino acid positions. Three-dimensional modelling of protein structures and calculation of electrostatic potentials for the implicated HLA alleles/amino acid substitutions demonstrated a correlation between the electrostatic potential of pocket P6 in HLA-DP molecules and the HLA-DPB1 alleles/amino acid substitutions conferring PBC susceptibility/protection, highlighting potential new avenues for future functional investigation

Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells

BACKGROUND AIMS: In patients with primary biliary cholangitis (PBC), the serum liver biochemistry measured during treatment with ursodeoxycholic acid-the UDCA response-accurately predicts long-term outcome. Molecular characterization of patients stratified by UDCA response can improve biological understanding of the high-risk disease, thereby helping to identify alternative approaches to disease-modifying therapy. In this study, we sought to characterize the immunobiology of the UDCA response using transcriptional profiling of peripheral blood mononuclear cell subsets. METHODS: We performed bulk RNA-sequencing of monocytes and TH1, TH17, TREG, and B cells isolated from the peripheral blood of 15 PBC patients with adequate UDCA response ("responders"), 16 PBC patients with inadequate UDCA response ("nonresponders"), and 15 matched controls. We used the Weighted Gene Co-expression Network Analysis to identify networks of co-expressed genes ("modules") associated with response status and the most highly connected genes ("hub genes") within them. Finally, we performed a Multi-Omics Factor Analysis of the Weighted Gene Co-expression Network Analysis modules to identify the principal axes of biological variation ("latent factors") across all peripheral blood mononuclear cell subsets. RESULTS: Using the Weighted Gene Co-expression Network Analysis, we identified modules associated with response and/or disease status (q<0.05) in each peripheral blood mononuclear cell subset. Hub genes and functional annotations suggested that monocytes are proinflammatory in nonresponders, but antiinflammatory in responders; TH1 and TH17 cells are activated in all PBC cases but better regulated in responders; and TREG cells are activated-but also kept in check-in responders. Using the Multi-Omics Factor Analysis, we found that antiinflammatory activity in monocytes, regulation of TH1 cells, and activation of TREG cells are interrelated and more prominent in responders. CONCLUSIONS: We provide evidence that adaptive immune responses are better regulated in patients with PBC with adequate UDCA response

Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs). We characterized the phenotypic response to UDCA based on BA and bacterial profiles of PBC patients treated with UDCA. Patients from the UK-PBC cohort (n = 419) treated with UDCA for a minimum of 12-months were assessed using the Barcelona dynamic response criteria. BAs from serum, urine, and feces were analyzed using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry and fecal bacterial composition measured using 16S rRNA gene sequencing. We identified 191 non-responders, 212 responders, and a subgroup of responders with persistently elevated liver biomarkers (n = 16). Responders had higher fecal secondary and tertiary BAs than non-responders and lower urinary bile acid abundances, with the exception of 12-dehydrocholic acid, which was higher in responders. The sub-group of responders with poor liver function showed lower alpha-diversity evenness, lower abundance of fecal secondary and tertiary BAs than the other groups and lower levels of phyla with BA-deconjugation capacity (Actinobacteriota/Actinomycetota, Desulfobacterota, Verrucomicrobiota) compared to responders. UDCA dynamic response was associated with an increased capacity to generate oxo-/epimerized secondary BAs. 12-dehydrocholic acid is a potential biomarker of treatment response. Lower alpha-diversity and lower abundance of bacteria with BA deconjugation capacity might be associated with an incomplete response to treatment in some patients

The Serum Proteome and Ursodeoxycholic Acid Response in Primary Biliary Cholangitis.

Funder: UK‐PBC MRC Stratified MedicineFunder: Pfizer; Id: http://dx.doi.org/10.13039/100004319BACKGROUND AND AIMS: Stratified therapy has entered clinical practice in primary biliary cholangitis (PBC), with routine use of second-line therapy in nonresponders to first-line therapy with ursodeoxycholic acid (UDCA). The mechanism for nonresponse to UDCA remains, however, unclear and we lack mechanistic serum markers. The UK-PBC study was established to explore the biological basis of UDCA nonresponse in PBC and identify markers to enhance treatment. APPROACH AND RESULTS: Discovery serum proteomics (Olink) with targeted multiplex validation were carried out in 526 subjects from the UK-PBC cohort and 97 healthy controls. In the discovery phase, untreated PBC patients (n = 68) exhibited an inflammatory proteome that is typically reduced in scale, but not resolved, with UDCA therapy (n = 416 treated patients). Nineteen proteins remained at a significant expression level (defined using stringent criteria) in UDCA-treated patients, six of them representing a tightly linked profile of chemokines (including CCL20, known to be released by biliary epithelial cells (BECs) undergoing senescence in PBC). All showed significant differential expression between UDCA responders and nonresponders in both the discovery and validation cohorts. A linear discriminant analysis, using serum levels of C-X-C motif chemokine ligand 11 and C-C motif chemokine ligand 20 as markers of responder status, indicated a high level of discrimination with an AUC of 0.91 (CI, 0.83-0.91). CONCLUSIONS: UDCA under-response in PBC is characterized by elevation of serum chemokines potentially related to cellular senescence and was previously shown to be released by BECs in PBC, suggesting a potential role in the pathogenesis of high-risk disease. These also have potential for development as biomarkers for identification of high-risk disease, and their clinical utility as biomarkers should be evaluated further in prospective studies

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist