Negotiating Closed Doors and Constraining Deadlines: The Potential of Visual Ethnography to Effectually Explore Private and Public Spaces of Motherhood and Parenting

Pregnancy and motherhood are increasingly subjected to surveillance, by medical professionals, the media and the general public; and discourses of ideal parenting are propagated alongside an admonishment of the perceived ‘failing’ maternal subject. However, despite this scrutiny, the mundane activities of parenting are often impervious to ethnographic forms of inquiry. Challenges for ethnographic researchers include the restrictions of becoming immersed in the private space of the home where parenting occurs, and an institutional structure that discourages exploratory and long-term fieldwork. This paper draws on four studies, involving 34 participants, which explored their journeys into the space of parenthood and their everyday experiences. The studies all employed forms of visual ethnography including artefacts, photo-elicitation, timelines, collage and sandboxing. The paper argues that visual methodologies can enable access to unseen aspects of parenting, and engender forms of temporal extension, which can help researchers to disrupt the restrictions of tightly time bounded projects

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Investigating perfusion and hypoxia in the human uterus

Abstract. Introduction: Heavy menstrual bleeding (HMB) is a common and debilitating condition. Current treatment options are limited by lack of effectiveness, side effects and surgical risks. Better understanding of the physiology of menstruation may help identify new therapeutic targets. Transient vasoconstriction of the endometrial spiral arterioles occurs prior to menstruation. There is in vitro evidence that endometrial hypoxia is present at menstruation and activates endometrial repair and that a decreased hypoxic response may result in HMB. Determination of hypoxia in vivo has not yet been possible in the human endometrium. Magnetic resonance imaging (MRI) techniques may be utilised to non-invasively detect markers of endometrial hypoxia in women.Obesity, defined as a body mass index (BMI) ≥30 kg/m2, has a profound impact on health and its prevalence is rising worldwide. However, there are limited data on the influence of obesity on menstrual blood loss (MBL). Therefore, it was hypothesised that: 1.Hypoxia is present in the human endometrium at menstruation and can be detected in vivo and ex vivo.2.Women with objectively measured HMB have a defective endometrial hypoxic response during menstruation.3.MRI assessments of endometrial hypoxia correlate with laboratory-based techniques in the detection of hypoxia markers. 4.Obesity in women is associated with increased MBL due to an impaired endometrial hypoxic response at menstruation. Methods: 24 participants were recruited and underwent measurement of MBL using the modified alkaline haematin method (HMB: ≥80 ml) and attended for MRI scans timed for the menstrual and early/mid-secretory phase of the menstrual cycle. To address hypotheses 1-3, the protocol included T2* quantification and dynamic contrast-enhanced MRI (DCE-MRI). An endometrial sample was also collected in the menstrual and early/mid-secretory cycle phase for laboratory analysis of hypoxia markers: CAIX (a hypoxia marker) analysed by immunohistochemistry (IHC) and hypoxia-regulated repair factors (ADM, VEGFA, CXCR4) and lactate dehydrogenase (LDHA) measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Endometrial vasculature was also analysed by immunofluorescence for CD-31 (endothelial cell marker) and α-SMA (marker of vascular smooth muscle cells).To assess hypothesis 4, women (n=122) completed a pictorial bleeding assessment chart (PBAC) and had their BMI measured. Endometrial samples were also collected from 28 women in the menstrual/late-secretory cycle phase to assess for hypoxic markers as above. Results: In vivo imaging revealed women with normal menstrual bleeding (NMB; <80 ml) had reduced endometrial T2* at menstruation compared to the non-menstrual phase. Deoxyhaemoglobin increases local magnetic field inhomogeneity which decreases T2*, hence these data are consistent with hypoxia at menses. Endometrial plasma flow (Fp) was increased at menstruation compared to the non-menstrual phase which may reflect post hypoxic vasodilation of the spiral arterioles within the endometrium. Ex vivo findings in women with NMB showed increased levels of ADM, VEGF-A, CXCR4 and LDHA mRNA in paired menstrual compared to non-menstrual endometrium, supporting the presence of endometrial hypoxia at menstruation. Comparing women with NMB and HMB, in vivo imaging showed no difference in T2* at menstruation. However, endometrial Fp and plasma volume (vp) were reduced at menstruation in women with HMB compared to NMB. This may reflect delayed initiation of endometrial repair or a lack of post hypoxic vasodilation within the endometrium of women with HMB. There were no differences in laboratory analyses of endometrial hypoxic markers at menstruation between these two groups of women. A significant negative correlation between T2* and endometrial concentrations of ADM, VEGF-A, CXCR4 was observed providing validation of this non-invasive technique for the detection of endometrial hypoxia in vivo.There was a positive correlation between BMI and MBL but no evidence that obesity impairs endometrial hypoxia at menstruation. In summary, the novel in vivo and ex vivo data presented in this thesis support the presence of hypoxia in the endometrium of women with NMB. Women with HMB displayed altered endometrial perfusion at menstruation. Non-invasive imaging may improve diagnosis and provide opportunity for identification of personalised targets for the management of HMB

Chronic pelvic pain

Chronic pelvic pain is a major public health problem that impacts all areas of a woman's life. The diagnosis is frequently difficult and delayed with women often presenting to a variety of specialties and undergoing multiple investigations before a diagnosis is reached. Aetiology is frequently multifactorial with both precipitating and perpetuating factors. Optimal management is within a multidisciplinary team who can fully address the range of factors that may maintain pelvic pain

Involving lived experience in regional efforts to address gambling-related harms: going beyond ‘window dressing’ and ‘tick box exercises’

Abstract Background Lived Experience (LE) involvement has been shown to improve interventions across diverse sectors. Yet LE contributions to public health approaches to address gambling-related harms remain underexplored, despite notable detrimental health and social outcomes linked to gambling. This paper analyses the potential of LE involvement in public health strategy to address gambling-related harms. It focuses on the example of a UK city-region gambling harms reduction intervention that presented multiple opportunities for LE input. Methods Three focus groups and 33 semi-structured interviews were conducted to hear from people with and without LE who were involved in the gambling harms reduction intervention, or who had previous experience of LE-informed efforts for addressing gambling-related harms. People without LE provided reflections on the value and contributions of others’ LE to their work. Data analysis combined the Framework Method with themes developed inductively (from people’s accounts) and deductively (from the literature, including grey literature). Results Four themes were identified: (1) personal journeys to LE involvement; (2) the value added by LE to interventions for addressing gambling-related harms; (3) emotional impacts on people with LE; and (4) collective LE and diverse lived experiences. Two figures outlining LE involvement specific to gambling harms reduction in the UK, where public health efforts aimed at addressing gambling-related harms coexist with industry-funded programmes, are proposed. Conclusions Integrating a range of LE perspectives in a public health approach to gambling harms reduction requires local access to involvement for people with LE via diverse routes that are free from stigma and present people with LE with options in how they can engage and be heard in decision-making, and how they operate in relation to industry influence. Involving LE in gambling harms reduction requires enabling people to develop the affective and critical skills necessary to navigate complex emotional journeys and a challenging commercial and policy environment