'Nesting networks': Women's experiences of social network support in high-risk pregnancy.

OBJECTIVE: Social support, an individual's social relationships (both online and offline), may provide protection against adverse mental health outcomes, such as anxiety and depression, which are high in women who have been hospitalised with high-risk pregnancy. This study explored the social support available to women at higher risk of preeclampsia during pregnancy by examining personal social networks. DESIGN: Semi-structured interviews were accompanied by social network mapping using the web-based social networking tool GENIE. SETTING: England. PARTICIPANTS: Twenty-one women were recruited, of whom 18 were interviewed both during pregnancy and postnatally between April 2019 and April 2020. Nineteen women completed maps pre-natally, 17 women completed maps pre-natally and post-natally. Women were taking part in the BUMP study, a randomised clinical trial that included 2441 pregnant individuals at higher risk of preeclampsia and recruited at a mean of 20 weeks' gestation from 15 hospital maternity units in England between November 2018 and October 2019. RESULTS: Women's social networks tightened during pregnancy. The inner network changed most dramatically postnatally with women reporting fewer network members. Interviews revealed networks were primarily 'real-life' rather than online social networks, with members providing emotional, informational, and practical support. Women with a high-risk pregnancy valued the relationships they developed with health professionals during pregnancy, and would like their midwife to have a more central role in their networks by providing informational and, where needed, emotional support. The social network mapping data supported the qualitative accounts of changing networks across high-risk pregnancy. CONCLUSION: Women with a high-risk pregnancy seek to build "nesting networks" to support them through pregnancy into motherhood. Different types of support are sought from trusted sources. Midwives can play a key role. PRACTICE IMPLICATIONS: As well as highlighting other potential needs during pregnancy and the ways in which they can be met, support from midwives has a key role. Through talking to women early in their pregnancy, signposting information and explaining ways to contact health professionals regarding informational or emotional support would fill a gap that currently is met by other aspects of their network.

Boundary spanning and identity work in the clinical research delivery workforce: a qualitative study of research nurses, midwives and allied health professionals in the National Health Service, United Kingdom.

BACKGROUND: Research nurses, midwives and allied health professionals are members of an important emergent profession delivering clinical research and, in the United Kingdom, have been the focus of considerable investment by the National Institute for Health Research (NIHR). This paper considers the experiences of research nurses, midwives and allied health professionals in relation to professional identity work, recognizing these are coproduced alongside others that they interact with (including patients, clinical staff and other research staff). METHODS: Semi-structured interviews were conducted with 45 nurses, midwives and allied health professionals in the UK about their experiences of working in research delivery. Interviews were transcribed verbatim and thematically coded and analysed. RESULTS: Our analysis highlights how research nurses, midwives and allied health professionals adjust to new roles, shift their professional identities and undertake identity work using uniforms, name badges and job titles as they negotiate complex identities. CONCLUSIONS: Research nurses, midwives and allied health professionals experience considerable challenges as they enter and transition to a research delivery role, with implications for their sense of professional identities. A change in the work that they undertake and how they are (or perceive they are) viewed by others (including clinical non-research colleagues and patients) has implications for their sense of professional and individual identity. The tensions involved extend to their views on symbols of professional identity, such as uniforms, and as they seek to articulate and demonstrate the value of their conjoined role in research and as a healthcare professional, within the unfolding landscape of health research. We embed our study findings in the context of the newly emerging clinical research practitioner workforce, which further exacerbates and complicates the role and identity complexity for nurses, midwives and allied health professionals in research delivery.

Parents' experiences of care following the loss of a baby at the margins between miscarriage, stillbirth and neonatal death: a UK qualitative study.

OBJECTIVE: To explore the healthcare experiences of parents whose baby died either before, during or shortly after birth between 20+0 and 23+6  weeks of gestation in order to identify practical ways to improve healthcare provision. DESIGN: Qualitative interview study. SETTING: England through two parent support organisations and four NHS Trusts. SAMPLE: A purposive sample of parents. METHODS: Thematic analysis of semi-structured in-depth narrative interviews. MAIN OUTCOME MEASURES: Parents' healthcare experiences. RESULTS: The key overarching theme to emerge from interviews with 38 parents was the importance of the terminology used to refer to the death of their baby. Parents who were told they were 'losing a baby' rather than 'having a miscarriage' were more prepared for the realities of labour, the birth experience and for making decisions around seeing and holding their baby. Appropriate terminology validated their loss, and impacted on parents' health and wellbeing immediately following bereavement and in the longer term. CONCLUSION: For parents experiencing the death of their baby at the margins between miscarriage, stillbirth and neonatal death, ensuring the use of appropriate terminology that reflects parents' preferences is vital. This helps to validate their loss and prepare them for the experiences of labour and birth. Reflecting parents' language preferences combined with compassionate bereavement care is likely to have a positive impact on parents' experiences and improve longer-term outcomes. TWEETABLE ABSTRACT: Describing baby loss shortly before 24 weeks of gestation as a 'miscarriage' does not prepare parents for labour and birth, seeing their baby and making memories.

Women's and healthcare providers' perceptions of long-term complications associated with hypertension and diabetes in pregnancy: a qualitative study.

OBJECTIVES: A diagnosis of hypertensive disorders during pregnancy (HDPs) or gestational diabetes mellitus (GDM) is highly predictive of women at increased risk of developing chronic hypertension, Type 2 diabetes, and cardiovascular disease. This study investigates perceptions of women and healthcare providers in rural India regarding these long-term risks. DESIGN: Qualitative study using modified grounded theory. SETTING: Two states in rural India: Haryana and Andhra Pradesh. POPULATION: Pregnant and postpartum women, community health workers (CHWs), primary care physicians, obstetricians, laboratory technicians, and healthcare officials. METHODS: In-depth interviews and focus group discussions explored: (1) priorities for high-risk pregnant women; (2) detection and management of HDPs and GDM; (3) postpartum management, and (4) knowledge of long-term sequelae of high-risk conditions. A thematic analysis was undertaken. RESULTS: Seven focus group discussions and 11 in-depth interviews (n = 71 participants) were performed. The key priority area for high-risk pregnant women was anaemia. Blood pressure measurement was routinely embedded in antenatal care; however, postpartum follow up and knowledge of the long-term complications were limited. GDM was not considered a common problem, although significant variations and challenges to GDM screening were identified. Knowledge of the long-term sequelae of GDM with regard to an increased risk of Type 2 diabetes and cardiovascular disease among doctors was minimal. CONCLUSIONS: There is a need for improved education, standardisation of testing and postpartum follow up of HDPs and GDM in rural Indian settings. FUNDING: SN is supported by an MRC Clinical Research Training Fellowship (MR/R017182/1). The George Institute for Global Health Global Women's Health programme provided financial support for the research assistant and fieldwork costs in India. TWEETABLE ABSTRACT: Improved education and postpartum care of women with hypertension and diabetes in pregnancy in rural India are needed to prevent long-term risks.

What outcomes should researchers select, collect and report in pre-eclampsia research? A qualitative study exploring the views of women with lived experience of pre-eclampsia.

OBJECTIVE: To identify outcomes relevant to women with lived experience of pre-eclampsia. DESIGN: Qualitative interview study. SETTING: A national study conducted in the United Kingdom. SAMPLE: Purposive sample of women with lived experience of pre-eclampsia. METHODS: Thematic analysis of qualitative interview transcripts. RESULTS: Thirty women with lived experience of pre-eclampsia were interviewed. Thematic analysis identified 71 different treatment outcomes. Fifty-nine of these had been previously reported by pre-eclampsia trials. Outcomes related to maternal and neonatal morbidity, commonly reported by pre-eclampsia trials, were frequently discussed by women with lived experience of pre-eclampsia. Twelve outcomes had not been previously reported by pre-eclampsia trials. When compared with published research, it was evident that the outlook of women with lived experience of pre-eclampsia was broader. They considered pre-eclampsia in relation to the 'whole' person and attached special significance to outcomes relating to emotional wellbeing and the future health, development and wellbeing of their offspring. CONCLUSIONS: Selecting, collecting and reporting outcomes relevant to women with pre-eclampsia should ensure that future pre-eclampsia research has the necessary reach and relevance to inform clinical practice. Future core outcome set development studies should use qualitative research methods to ensure that the long list of potential core outcomes holds relevance to patients. TWEETABLE ABSTRACT: What do women want? A national study identifies key treatment outcomes for women with pre-eclampsia. Next step: @coreoutcomes for #preeclampsia @NIHR_DC.

Female genital mutilation in the UK- where are we, where do we go next? Involving communities in setting the research agenda.

BACKGROUND: Female Genital Mutilation (FGM) is all practices involving cutting, alteration or injury to the female genitalia for non-medical reasons. It is a form of violence against women and children, with no benefits and many harms. In 2014, the UK Government committed to working to eliminate FGM. Steps taken towards this aim included creation of educational and safeguarding resources for professionals, and legislative changes including a mandatory reporting duty for professionals in England and Wales (where if a girl under 18 discloses or is found on examination to have FGM then the professional is mandated to report this to the police), and an FGM Enhanced Dataset applicable to NHS organisations in England requiring the submission of personal data about women and girls who have had FGM to NHS Digital. To date, compliance with dataset returns from primary care services have been low. This report describes using patient and public involvement (PPI) to identify research and service priorities to support communities affected by FGM. METHODS: We held a series of PPI events (4 focus groups, and a multi-agency seminar) in 2015-2016, following the introduction of these legislative changes, speaking to community members, and professionals involved in their care. We asked participants to consider what they identified as research, knowledge and service priorities to support communities affected by FGM. RESULTS: The impact of these legislative and reporting requirements on the trust needed for community members to seek to consult health services was identified as important for further research. Priorities for service development were holistic services, that met a woman's needs throughout her lifecourse. Participants emphasised the importance of understanding how to listen, involve and utilise community voices in developing education for professionals, designing services, and developing policy. CONCLUSIONS: There was a desire for change to develop from within affected communities; any learning and resources need to be co-created and constructed in such a way that they can be effectively shared between women, communities, and professionals. Questions remain about how to define community consultation, how to recognise when it was adequate, and how to hear beyond community activists to hear a wider range of voices.

Experiences of the quality of care of women with near-miss maternal morbidities in the UK.

We undertook a qualitative interview study of women's and their partners' experiences of severe pregnancy complications. Across the care pathway, women identified a number of examples of good practice that made an important difference to their recovery. There were some areas where women felt the quality of care could be improved, for example during points of transition between higher level and routine care or from hospital to the community. Longer-term support and counselling were felt to be particularly valuable, and yet not always universally available. These results emphasise the importance of integrated quality care across the whole patient pathway.

Three dimensional structure of the anthrax toxin translocon-lethal factor complex by cryo-electron microscopy.

We have visualized by cryo-electron microscopy (cryo-EM) the complex of the anthrax protective antigen (PA) translocon and the N-terminal domain of anthrax lethal factor (LF(N) inserted into a nanodisc model lipid bilayer. We have determined the structure of this complex at a nominal resolution of 16 Å by single-particle analysis and three-dimensional reconstruction. Consistent with our previous analysis of negatively stained unliganded PA, the translocon comprises a globular structure (cap) separated from the nanodisc bilayer by a narrow stalk that terminates in a transmembrane channel (incompletely distinguished in this reconstruction). The globular cap is larger than the unliganded PA pore, probably due to distortions introduced in the previous negatively stained structures. The cap exhibits larger, more distinct radial protrusions, previously identified with PA domain three, fitted by elements of the NMFF PA prepore crystal structure. The presence of LF(N), though not distinguished due to the seven-fold averaging used in the reconstruction, contributes to the distinct protrusions on the cap rim volume distal to the membrane. Furthermore, the lumen of the cap region is less resolved than the unliganded negatively stained PA, due to the low contrast obtained in our images of this specimen. Presence of the LF(N) extended helix and N terminal unstructured regions may also contribute to this additional internal density within the interior of the cap. Initial NMFF fitting of the cryoEM-defined PA pore cap region positions the Phe clamp region of the PA pore translocon directly above an internal vestibule, consistent with its role in toxin translocation.

Frequency of truly cryptic subtelomere abnormalities--a study of 534 patients and literature review.

Frequency of truly cryptic subtelomere abnormalities - a study of 534 patients and literature review. Unbalanced subtelomere chromosome rearrangements are a significant cause of mental retardation with approximately 5% of over 3000 affected individuals tested worldwide having a chromosome rearrangement of this type. Many of these abnormalities are detectable using routine karyotyping at the 550 band level and therefore are not considered to be cryptic. The frequency of truly cryptic subtelomere abnormality should be less than 5% but has not been established. In this study, we defined 'cryptic abnormality' as one not detectable at the 550 band level on routine karyotyping. Using this as one of the selection criteria, we have studied 534 individuals with mental retardation/ developmental delay (MR/DD) and referred for subtelomere study by clinical geneticists. We have identified seven cases with cryptic subtelomere abnormalities. The clinical features of the seven abnormal cases are summarized. Literature review identified five publications on the identification of subtelomere abnormalities which used similar recruitment criteria: (a) normal karyotype at the 550 band level and (b) subjects were selected for subtelomere studies. Combining the data from these studies with those of the current study, 1154 patients were tested and 30 subtelomere abnormalities were identified. We estimate the frequency of truly cryptic subtelomere abnormality to be approximately 2.6% (30/1154) in children with MR/DD who are referred for subtelomere study.

The Hunter-McAlpine syndrome results from duplication 5q35-qter.

In 1977 Hunter et al. J Med Genet 1977: 14 (6): 430-437, reported a family with six affected members, connected over three generations through unaffected individuals. Subsequently, several other patients purported to have the condition were reported. The condition became known as the Hunter-McAlpine syndrome, and there was debate as to whether or not it was identical to the Ruvalcaba syndrome or a type of tricho-rhino-phalangeal syndrome. In this article we confirm that the original family and a patient reported by Ades et al. Clin Dysmorphol 1993: 2 (2): 123-130 have cryptic translocations resulting in duplication of 5q35-qter. Similarities are noted between our patients and others in the literature with duplication of this chromosome segment.

A familial cryptic subtelomeric deletion 12p with variable phenotypic effect.

A 15-year-old-boy and his mother, both carrying a cryptic deletion within 12p13.33, are described. The proband has a mild phenotype with moderate mental retardation and severe behavioural problems. The mother had some learning difficulties at school. Conventional GTL-banded high-resolution chromosome analysis showed normal karyotypes. Subsequent analysis by fluorescence in situ hybridization using a set of probes specific for the subtelomeric regions of all chromosomes, plus a series of probes at 12p13.33 extending from the 12p telomere, showed that both mother and son carry a 1.65 Mb terminal deletion in this region. There are 10 predicted genes within the deleted region. The unanticipated familial nature of the deletion emphasizes the value of family studies in all cases with subtelomeric abnormalities. It also demonstrates the difficulty in making a clinical diagnosis of individuals with this deletion. To the best of the present authors' knowledge, the proband and his mother are the first patients described with a submicroscopic deletion at 12p13.33.

Acculturation and the prevalence of depression in older Mexican Americans: baseline results of the Sacramento Area Latino Study on Aging.

OBJECTIVE: To determine the association between acculturation, immigration, and prevalence of depression in older Mexican Americans. DESIGN: Cross-sectional analysis from a cohort study. SETTING: Urban and rural counties of the Central Valley of Northern California. PARTICIPANTS: One thousand seven hundred and eighty-nine Latinos recruited from a population-based sample (85% Mexican Americans) with a mean age of 70.6 (range 60-100; standard deviation (SD) = 7.13); 58.2% were women. MEASUREMENTS: Depressive symptoms were assessed with the Center for Epidemiologic Studies--Depression scale (CES-D). Acculturation was measured with the Acculturation Rating Scale for Mexican Americans--II. Psychosocial, behavioral, and medical histories were also obtained. RESULTS: The prevalence of depression (CES-D > or = 16) was 25.4%. Women were at greater risk (32.0%) than men (16.3%; male/female odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.90-3.09). The prevalence of depression was higher among immigrants (30.4%, OR = 1.70, 95% CI = 1.36-2.13), bicultural participants (24.2%, OR = 1.66, 95% CI = 1.24-2.24), and less-acculturated participants (36.1%, OR = 2.95, 95% CI = 2.22-3.93) compared with U.S.-born (20.5%) and more-acculturated groups (16.1%). When adjustments for education, income, psychosocial, behavioral, and health-problem factors were made, the least-acculturated participants were at significantly higher risk of depression than highly acculturated Mexican Americans (OR = 1.56, 95% CI = 1.06-2.31). CONCLUSIONS: These findings are consistent with previously reported estimates of a higher prevalence of depression for older Mexican Americans than non-Hispanic Caucasians and African Americans and are the first to report the prevalence and risk of depression for older U.S.-born and immigrant Mexican Americans. The high prevalence of depression of the least acculturated group may be related to cultural barriers encountered by immigrants and less-acculturated older Mexican Americans and to poorer health status.

Physical and radiation hybrid mapping of canine chromosome 12, in a region corresponding to human chromosome 6p12-q12.

The positional cloning of the hypocretin receptor 2, the gene for autosomal recessive canine narcolepsy, has led to the development of a physical map spanning a large portion of canine chromosome 12 (CFA12), in a region corresponding to human chromosome 6p12-q13. More than 40 expressed sequence tags (ESTs) were used in homology search experiments, together with chromosome walking, to build both physical and radiation hybrid maps of the CFA12 13-21 region. The resulting map of bacterial artificial chromosome ends, ESTs, and microsatellite markers represents the longest continuous high-density map of the dog genome reported to date. These data further establish the dog as a system for studying disease genes of interest to human populations and highlight feasible approaches for positional cloning of disease genes in organisms where genomic resources are limited.

Working with culture: a qualitative analysis of barriers to the recruitment of Chinese-American family caregivers for dementia research.

The National Institutes of Health is making efforts to increase the representation of minority elders in aging research. While it is often noted that cultural barriers may make the recruitment of minority elders into research more difficult, relatively little empirical exists to support this claim. The purpose of this study was to identify sociocultural barriers to recruitment that emerged during a four-year study of dementia caregiving among Chinese families in the Boston area. More specifically, this paper examines how culturally shaped conceptions of health, aging, and dementia impacted the recruitment process. This paper is based on a qualitative analysis of interviews with 23 Chinese families and extensive fieldnotes generated by project ethnographers and interviewers. The following themes emerged in this analysis: 1) dementia-related changes were construed as a normal part of the aging process rather than a disease, making it more difficult to identify dementia-affected elders and to recruit families, 2) research participation was viewed as potentially harmful because it can lead to excessive worry 3) Alzheimer's disease carries a social stigma among Chinese, leading families to shun formal diagnosis and research participation, and 4) practitioners viewed research as an intrusion offering no direct benefit to participants.

Construction and characterization of an eightfold redundant dog genomic bacterial artificial chromosome library.

A large insert canine genomic bacterial artificial chromosome (BAC) library was built from a Doberman pinscher. Approximately 166,000 clones were gridded on nine high-density hybridization filters. Insert analysis of randomly selected clones indicated a mean insert size of 155 kb and predicted 8.1 coverage of the canine genome. Two percent of the clones were nonrecombinant. Chromosomal fluorescence in situ hybridization studies of 60 BAC clones indicated no chimerism. The library was hybridized with dog PCR products representing eight genes (ADA, TNFA, GCA, MYB, HOXA, GUSB, THY1, and TOP1). The resulting positive clones were characterized and shown to be compatible with an eightfold redundant library.

Genetic studies in narcolepsy, a disorder affecting REM sleep.

Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal manifestations of rapid eye movement (REM) sleep including cataplexy, sleep paralysis, and hypnagogic hallucinations. It is known to be a complex disorder, with both genetic predisposition and environmental factors playing a role. In humans, susceptibility to narcolepsy is tightly associated with a specific HLA allele, DQB1*0602. In humans and canines, most cases are sporadic. In Doberman pinschers and Labrador retrievers, however, the disease is transmitted as an autosomal recessive gene canarc-1 with full penetrance. This gene is not linked with the dog leukocyte antigen complex, but is tightly linked with a marker with high homology to the human mu-switch immunoglobulin gene. We have isolated several genomic clones encompassing the canarc-1 marker and the variable heavy chain immunoglobulin region in canines. These have been partially sequenced and have been mapped onto specific dog chromosomes by fluorescence in situ hybridization (FISH). Our results indicate that the mu-switch-like marker is not part of the canine immunoglobulin machinery. We are continuing to extend the genomic contig using a newly developed canine BAC library and attempting to identify the corresponding human region of conserved synteny.

A survey of depressive symptoms among Vietnamese-American men in three locales: prevalence and correlates.

Vietnamese are one of the fastest growing ethnic minority groups in the United States. The purpose of this study was to determine the prevalence and correlates of high depression scores among Vietnamese men in three locales. Computer assisted telephone interviews were conducted with adult Vietnamese men in San Francisco/Alameda Counties, Santa Clara County, and the city of Houston. Telephone numbers of households with Vietnamese surnames were chosen randomly from area telephone books. Depression was assessed using a previously validated Vietnamese language depression screening instrument with 86% sensitivity and 96% specificity for major depression. Between 8.2% and 9.8% of the men scored above the cut-off. Logistic regression analysis revealed that men who were the least proficient in English, poorer, unemployed or disabled, veterans, and those living in Houston were more likely to have a high depression score. Based on the characteristics of the screening instrument, rates of clinical depression among Vietnamese men may be modestly higher than rates for men in the general population. However, high-risk subgroups identified by our analyses may suffer from substantially higher rates of clinical depression. To our knowledge, ours is the first study to show that community context or locale is an independent predictor of high depressive symptoms in this population. These findings have important implications for prevention and intervention approaches to depression among Vietnamese men.

A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.

Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.