Women's experience of transfer from midwifery unit to hospital obstetric unit during labour: a qualitative interview study.

Acknowledgements RER was funded by a Researcher Development Award from the National Institute for Health Research (NIHR) (RDA/03/07/066). The views expressed in this paper are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors would like to thank the midwives and voluntary organisations who helped with recruitment and, in particular, all the women who took part in the study.Peer reviewedPublisher PD

Incidence and risk factors for placenta accreta/increta/percreta in the UK: a national case-control study.

Placenta accreta/increta/percreta is associated with major pregnancy complications and is thought to be becoming more common. The aims of this study were to estimate the incidence of placenta accreta/increta/percreta in the UK and to investigate and quantify the associated risk factors

Cardiac action of the first G protein biased small molecule apelin agonist.

Apelin peptide analogues displaying bias towards G protein signalling pathways have beneficial cardiovascular actions compared with the native peptide in humans in vivo. Our aim was to determine whether small molecule agonists could retain G protein bias. We have identified a biased small molecule, CMF-019, and characterised it in vitro and in vivo. In competition radioligand binding experiments in heart homogenates, CMF-019 bound to the human, rat and mouse apelin receptor with high affinity (pKi=8.58±0.04, 8.49±0.04 and 8.71±0.06 respectively). In cell-based functional assays, whereas, CMF-019 showed similar potency for the Gαi pathway to the endogenous agonist [Pyr(1)]apelin-13 (pD2=10.00±0.13 vs 9.34±0.15), in β-arrestin and internalisation assays it was less potent (pD2=6.65±0.15 vs 8.65±0.10 and pD2=6.16±0.21 vs 9.28±0.10 respectively). Analysis of these data demonstrated a bias of ∼400 for the Gαi over the β-arrestin pathway and ∼6000 over receptor internalisation. CMF-019 was tested for in vivo activity using intravenous injections into anaesthetised male Sprague-Dawley rats fitted with a pressure-volume catheter in the left ventricle. CMF-019 caused a significant increase in cardiac contractility of 606±112mmHg/s (p<0.001) at 500nmol. CMF-019 is the first biased small molecule identified at the apelin receptor and increases cardiac contractility in vivo. We have demonstrated that Gαi over β-arrestin/internalisation bias can be retained in a non-peptide analogue and predict that such bias will have the therapeutic benefit following chronic use. CMF-019 is suitable as a tool compound and provides the basis for design of biased agonists with improved pharmacokinetics for treatment of cardiovascular conditions such as pulmonary arterial hypertension.British Heart Foundation [FS/14/59/31282]; Wellcome Trust [WT107715/Z/15/Z], Wellcome Trust Programme in Metabolic and Cardiovascular Disease [096822/Z/11/Z]; Medical Research Council [MRC MC PC 14116]; Pulmonary Hypertension Association UK; Cambridge Biomedical Research Centre Biomedical Resources Grant University of Cambridge [099156/Z/12/Z]; Engineering and Physical Sciences Research Council [EP/M506552/1]; Biomedical Health Research Centre, University of Leed

Religious perspectives on the use of psychopharmaceuticals as an enhancement technology

The use of psychopharmaceuticals as an enhancement technology has been the focus of attention in the bioethics literature. However, there has been little examination of the challenges that this practice creates for religious traditions that place importance on questions of being, authenticity and identity. We asked expert commentators from six major world religions to consider the issues raised by psychopharmaceuticals as an enhancement technology. These commentaries reveal that in assessing the appropriate place of medical therapies, religious traditions, like secular perspectives, rely upon ideas about health and disease and about normal human behavior. But unlike secular perspectives, faith traditions explicitly concern themselves with ways in which medicine should or should not be used to live a ‘good life’. KEYWORDS: Enhancement; bioethics, psychopharmacology, religio

Electroweak Symmetry Breaking in the DSSM

We study the theoretical and phenomenological consequences of modifying the Kahler potential of the MSSM two Higgs doublet sector. Such modifications naturally arise when the Higgs sector mixes with a quasi-hidden conformal sector, as in some F-theory GUT models. In the Delta-deformed Supersymmetric Standard Model (DSSM), the Higgs fields are operators with non-trivial scaling dimension 1 < Delta < 2. The Kahler metric is singular at the origin of field space due to the presence of quasi-hidden sector states which get their mass from the Higgs vevs. The presence of these extra states leads to the fact that even as Delta approaches 1, the DSSM does not reduce to the MSSM. In particular, the Higgs can naturally be heavier than the W- and Z-bosons. Perturbative gauge coupling unification, a large top quark Yukawa, and consistency with precision electroweak can all be maintained for Delta close to unity. Moreover, such values of Delta can naturally be obtained in string-motivated constructions. The quasi-hidden sector generically contains states charged under SU(5)_GUT as well as gauge singlets, leading to a rich, albeit model-dependent, collider phenomenology.Comment: v3: 40 pages, 3 figures, references added, typos correcte

Radiographer gender and breast-screening uptake

BreastCheck, the Irish National Breast Screening Programme, screens women aged 50–64. Radiographer recruitment has been a challenge; doubling of numbers is required for full national expansion; to date females are employed. The aim was to document attitudes to male radiographers and effect on return for subsequent screening. In all 85.8% of a random sample of 2000 women recently screened by BreastCheck completed a postal questionnaire. The commonest reaction women felt they would have if there were a male radiographer was embarrassment; significantly greater among those attending a static unit (45.6%) than mobile (38.4%) and in younger women (46%) than older (38.7%). Nine per cent would not have proceeded if the radiographer was male and 9% would only have proceeded if female chaperone present. In all 17.5% (95% CI 15.7–19.4%) agreed that ‘If there were male radiographers I would not return for another screening appointment'; 18.3% were unsure. One-quarter agreed ‘if I heard there could be male radiographers it would change my opinion of BreastCheck for the worse'. The proportions agreeing with these statements did not vary significantly by screening unit type, age group, area of residence or insurance status. This is the largest published study to date of this important issue; the correct balance between equality and programme performance must be identified

Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile

Beyond maternal death: improving the quality of maternal care through national studies of ‘near-miss’ maternal morbidity

BACKGROUND: Studies of maternal mortality have been shown to result in important improvements to women’s health. It is now recognised that in countries such as the UK, where maternal deaths are rare, the study of near-miss severe maternal morbidity provides additional information to aid disease prevention, treatment and service provision. OBJECTIVES: To (1) estimate the incidence of specific near-miss morbidities; (2) assess the contribution of existing risk factors to incidence; (3) describe different interventions and their impact on outcomes and costs; (4) identify any groups in which outcomes differ; (5) investigate factors associated with maternal death; (6) compare an external confidential enquiry or a local review approach for investigating quality of care for affected women; and (7) assess the longer-term impacts. METHODS: Mixed quantitative and qualitative methods including primary national observational studies, database analyses, surveys and case studies overseen by a user advisory group. SETTING: Maternity units in all four countries of the UK. PARTICIPANTS: Women with near-miss maternal morbidities, their partners and comparison women without severe morbidity. MAIN OUTCOME MEASURES: The incidence, risk factors, management and outcomes of uterine rupture, placenta accreta, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, severe sepsis, amniotic fluid embolism and pregnancy at advanced maternal age (≥ 48 years at completion of pregnancy); factors associated with progression from severe morbidity to death; associations between severe maternal morbidity and ethnicity and socioeconomic status; lessons for care identified by local and external review; economic evaluation of interventions for management of postpartum haemorrhage (PPH); women’s experiences of near-miss maternal morbidity; long-term outcomes; and models of maternity care commissioned through experience-led and standard approaches. RESULTS: Women and their partners reported long-term impacts of near-miss maternal morbidities on their physical and mental health. Older maternal age and caesarean delivery are associated with severe maternal morbidity in both current and future pregnancies. Antibiotic prescription for pregnant or postpartum women with suspected infection does not necessarily prevent progression to severe sepsis, which may be rapidly progressive. Delay in delivery, of up to 48 hours, may be safely undertaken in women with HELLP syndrome in whom there is no fetal compromise. Uterine compression sutures are a cost effective second-line therapy for PPH. Medical comorbidities are associated with a fivefold increase in the odds of maternal death from direct pregnancy complications. External reviews identified more specific clinical messages for care than local reviews. Experience-led commissioning may be used as a way to commission maternity services. LIMITATIONS: This programme used observational studies, some with limited sample size, and the possibility of uncontrolled confounding cannot be excluded. CONCLUSIONS: Implementation of the findings of this research could prevent both future severe pregnancy complications as well as improving the outcome of pregnancy for women. One of the clearest findings relates to the population of women with other medical and mental health problems in pregnancy and their risk of severe morbidity. Further research into models of pre-pregnancy, pregnancy and postnatal care is clearly needed