Human gene copy number spectra analysis in congenital heart malformations

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≥200 kb) and losses (≥100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≤ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≤ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways

Understanding maternal postnatal blood pressure changes following hypertensive disorders in pregnancy: protocol for a prospective cohort study.

INTRODUCTION: Hypertensive disorders occur in approximately 10% of women during pregnancy. There is robust population-based data to show that women who have hypertension in pregnancy are much more likely to develop cardiovascular disease (CVD) in the postpartum period. Women with a hypertensive disorder of pregnancy (HDP) are twice more at risk of heart disease and stroke, and four times more likely to develop hypertension after birth. Two out of three women who had HDP will die from CVD. Recent evidence suggests that young women with HDP develop signs of CVD in the immediate postpartum period, rather than several decades later as previously presumed. If confirmed, this concerning finding presents healthcare practitioners with an opportunity to influence women's cardiovascular health by advising on lifestyle choices and considering therapeutic interventions to prevent the development of CVD. METHODS AND ANALYSIS: This prospective cohort study design will ask approximately 300 participants to complete 3 days of home blood pressure monitoring every fortnight for 12 weeks postpartum and will culminate with a 24-hour episode of ambulatory blood pressure monitoring at 12 weeks postpartum. Women and healthcare professionals will complete questionnaires surrounding postpartum care for women who had HDP and knowledge of CVD risk. In addition, the relationship between hypertension and factors likely to influence outcomes such as severity of HDP, maternal age, body mass index and ethnicity will be analysed using logistic regression. Blood pressure and data from questionnaires will be analysed using descriptive statistics, with temporal stratification. ETHICS AND DISSEMINATION: Research ethics approval was obtained from London-West London & GTAC Research Ethics Committee. Research outputs will be published and disseminated through midwifery, obstetric or general practitioner targeted academic journals. The patient and public involvement group will disseminate findings to women who have experienced HDP among their peer groups. TRIAL REGISTRATION NUMBER: NCT05137808

Breastfeeding support in low and middle-income countries: secondary analysis of national survey data

Background - Early initiation of breastfeeding and exclusive breastfeeding can reduce infant mortality. Breastfeeding support interventions such as counselling may improve adherence to recommended practices. However, it is not known if these interventions work at the population level. Objective - The aim of this study was to assess the relationship between early postnatal breastfeeding support and recommended breastfeeding practices. Design/setting - We pooled data from Demographic and Health Surveys in Africa (n=7), South East 20 Asia (n=2), the Americas (n=1), and Europe (n=1) to analyse these associations at the population level. Participants - We limited the data to the most recent live births in the two years before the survey, including 41431 births. Analysis - We fitted three multivariable logistic regression models to estimate the relationship between early postnatal breastfeeding support (a newborn postnatal check within an hour of birth plus counselling and observation of breastfeeding within two days) and three breastfeeding outcomes (early initiation of breastfeeding, absence of prelacteal feeding, and exclusive breastfeeding), adjusting for sociodemographic characteristics and birth-related factors. Findings - Early breastfeeding support was associated with a 24% increase (OR=1.24 95%CI=1.11,1.39) in the odds of initiating breastfeeding within one hour of birth. No relationships were found between breastfeeding support and prelacteal feeding in the first three days or exclusive breastfeeding at six months. Key conclusion - While postnatal breastfeeding counselling and observation may improve early initiation of breastfeeding, impact is not persistent for longer term breastfeeding outcomes. Implication for practice-Improved training for breastfeeding support and an enabling policy environment are required to improve breastfeeding practices for women and newborns

Improving inpatient postnatal services: midwives views and perspectives of engagement in a quality improvement initiative

Background: despite major policy initiatives in the United Kingdom to enhance women's experiences of maternity care, improving in-patient postnatal care remains a low priority, although it is an aspect of care consistently rated as poor by women. As part of a systems and process approach to improving care at one maternity unit in the South of England, the views and perspectives of midwives responsible for implementing change were sought. Methods: a Continuous Quality Improvement (CQI) approach was adopted to support a systems and process change to in-patient care and care on transfer home in a large district general hospital with around 6000 births a year. The CQI approach included an initial assessment to identify where revisions to routine systems and processes were required, developing, implementing and evaluating revisions to the content and documentation of care in hospital and on transfer home, and training workshops for midwives and other maternity staff responsible for implementing changes. To assess midwifery views of the quality improvement process and their engagement with this, questionnaires were sent to those who had participated at the outset. Results: questionnaires were received from 68 (46%) of the estimated 149 midwives eligible to complete the questionnaire. All midwives were aware of the revisions introduced, and two-thirds felt these were more appropriate to meet the women's physical and emotional health, information and support needs. Some midwives considered that the introduction of new maternal postnatal records increased their workload, mainly as a consequence of colleagues not completing documentation as required. Conclusions: this was the first UK study to undertake a review of in-patient postnatal services. Involvement of midwives at the outset was essential to the success of the initiative. Midwives play a lead role in the planning and organisation of in-patient postnatal care and it was important to obtain their feedback on whether revisions were pragmatic and achieved anticipated improvements in care quality. Their initial involvement ensured priority areas for change were identified and implemented. Their subsequent feedback highlighted further important areas to address as part of CQI to ensure best quality care continues to be implemented. Our findings could support other maternity service organisations to optimise in-patient postnatal services

Antenatal preventative pelvic floor muscle exercise intervention led by midwives to reduce postnatal urinary incontinence (APPEAL): protocol for a feasibility and pilot cluster randomised controlled trial

Background: Antenatal pelvic floor muscle exercises (PFME) in women without prior urinary incontinence (UI) are effective in reducing postnatal UI; however, UK midwives often do not provide advice and information to women on undertaking PFME, with evidence that among women who do receive advice, many do not perform PFME. Methods: The primary aim of this feasibility and pilot cluster randomised controlled trial is to provide a potential assessment of the feasibility of undertaking a future definitive trial of a midwifery-led antenatal intervention to support women to perform PFME in pregnancy and reduce UI postnatally. Community midwifery teams in participating NHS sites comprise trial clusters (n = 17). Midwives in teams randomised to the intervention will be trained on how to teach PFME to women and how to support them in undertaking PFME in pregnancy. Women whose community midwifery teams are allocated to control will receive standard antenatal care only. All pregnant women who give birth over a pre-selected sample month who receive antenatal care from participating community midwifery teams (clusters) will be sent a questionnaire at 10–12 weeks postpartum (around 1400–1500 women). Process evaluation data will include interviews with midwives to assess if the intervention could be implemented as planned. Interviews with women in both trial arms will explore their experiences of support from midwives to perform PFME during pregnancy. Data will be stored securely at the Universities of Birmingham and Exeter. Results will be disseminated through publications aimed at maternity service users, clinicians, and academics and inform a potential definitive trial of effectiveness. The West Midlands–Edgbaston Research Ethics Committee approved the study protocol. Discussion: Trial outcomes will determine if criteria to progress to a definitive cluster trial are met. These include women’s questionnaire return rates, prevalence of UI, and other health outcomes as reported by women at 10–12 weeks postpartum. Progress to a definitive trial however is likely to be prevented in the UK context by new perinatal pelvic health service, although this may be possible elsewhere. Trial registration: https://doi.org/10.1186/ISRCTN10833250. Registered 09/03/202

Opportunities, challenges and concerns for the implementation and uptake of pelvic floor muscle assessment and exercises during the childbearing years: protocol for a critical interpretive synthesis

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Pregnancy and childbirth are important risk factors for urinary incontinence (UI) in women. Pelvic floor muscle exercises (PFME) are effective for prevention of UI. Guidelines for the management of UI recommend offering pelvic floor muscle training (PFMT) to women during their first pregnancy as a preventive strategy. The objective of this review is to understand the relationships between individual, professional, inter-professional and organisational opportunities, challenges and concerns that could be essential to maximise the impact of PFMT during childbearing years and to effect the required behaviour change. METHODS: Following systematic searches to identify sources for inclusion, we shall use a critical interpretive synthesis (CIS) approach to produce a conceptual model, mapping the relationships between individual, professional, inter-professional and organisational factors and the implementation, acceptability and uptake of PFME education, assessment and training during the childbearing years. Purposive sampling will be used to identify potentially relevant material relating to topics or areas of interest which emerge as the review progresses. A wide range of empirical and non-empirical sources will be eligible for inclusion to encompass the breadth of relevant individual, professional, inter-professional and organisational issues relating to PFME during childbearing years. Data analysis and synthesis will identify key themes, concepts, connections and relationships between these themes. Findings will be interpreted in relation to existing frameworks of implementation, attitudes and beliefs of individuals and behaviour change. We will collate examples to illustrate relationships expressed in the conceptual model and identify potential links between the model and drivers for change. DISCUSSION: The CIS review findings and resulting conceptual model will illustrate relationships between factors that might affect the implementation, acceptability and uptake of PFME education, assessment and training during the childbearing years. The model will inform the development and evaluation of a training package to support midwives with implementation and delivery of effective PFME during the antenatal period. The review forms part of the first phase of the United Kingdom National Institute for Health Research funded 'Antenatal Preventative Pelvic floor Exercises And Localisation (APPEAL)' programme (grant number: RP-PG-0514-20002) to prevent poor health linked to pregnancy and childbirth-related UI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42016042792.The APPEAL project is funded by a National Institute for Health Research (NIHR) programme grant for applied research (RP-PG-0514-20002). MP and SD were supported in their contribution to the development of the research proposal by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. CM is part-funded by the CLAHRC West Midlands, and DB is part-funded by the CLAHRC South London

Using a discourse bank and a lexicon for the automatic identification of discourse connectives

We describe two new resources that have been prepared for European Portuguese and how they are used for discourse parsing: the Portuguese subpart of the TED-MDB corpus, a multilingual corpus of TED Talks that has been annotated in the PDTB style, and the Lexicon of Discourse Markers for Portuguese (LDM-PT). Both lexicon and corpus are used in a preliminary experiment for discourse connective identification in texts. This includes, in many cases, the difficult task of disambiguating between connective and non-connective uses. We annotated the PT-TED-MDB corpus with POS, lemma and syntactic constituency and focus on the 10 most frequent connectives in the corpus. The best approach considers word-form+POS+syntactic annotation and leads to 85% precision.info:eu-repo/semantics/publishedVersio

Tales from the Drop Zone: roles, risks and dramaturgical dilemmas

This paper critically revisits conventional understandings of ethnographic fieldwork roles, arguing that representations of the covert insider as heroic and adventurous are often idealistic and unrealistic. Drawing on one of the authors’ experiences of being both a covert and overt researcher in an ethnographic study of skydiving, we identify some of the dramaturgical dilemmas that can unexpectedly affect relations with participants throughout the research process. Our overall aim is to highlight how issues of trust, betrayal, exposure and vulnerability, together with the practical considerations of field research, combine to shape the researcher’s interactional strategies of identity work