Development of a core outcome set for effectiveness studies of breech birth at term (Breech-COS)-an international multi-stakeholder Delphi study: study protocol.

BACKGROUND: Women pregnant with a breech-presenting foetus at term are at increased risk of adverse pregnancy outcomes. The most common intervention used to improve neonatal outcomes is planned delivery by caesarean section. But this is not always possible, and some women prefer to plan a vaginal birth. A number of providers have proposed alternative interventions, such as delivery protocols or specialist teams, but heterogeneity in reported outcomes and their measurements prevents meaningful comparisons. The aim of this paper is to present a protocol for a study to develop a Breech Core Outcome Set (Breech-COS) for studies evaluating the effectiveness of interventions to improve outcomes associated with term breech birth. METHODS: The development of a Breech-COS includes three phases. First, a systematic literature review will be conducted to identify outcomes previously used in effectiveness studies of breech birth at term. A focus group discussion will be conducted with the study's pre-established Patient and Public Involvement (PPI) group, to enable service user perspectives on the results of the literature review to influence the design of the Delphi survey instrument. Second, an international Delphi survey will be conducted to prioritise outcomes for inclusion in the Breech-COS from the point of view of key stakeholders, including perinatal care providers and families who have experienced a term breech pregnancy. Finally, a consensus meeting will be held with stakeholders to ratify the Breech-COS and disseminate findings for application in future effectiveness studies. DISCUSSION: The expectation is that the Breech-COS will always be collected in all clinical trials, audits of practice and other forms of observation research that concern breech birth at term, along with other outcomes of interest. This will facilitate comparing, contrasting and combining studies with the ultimate goal of improved maternal and neonatal outcomes. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials (COMET) #1749

Pills and prayers: a comparative qualitative study of community conceptualisations of pre-eclampsia and pluralistic care in Ethiopia, Haiti and Zimbabwe.

BACKGROUND: Pre-eclampsia is a leading cause of preventable maternal and perinatal deaths globally. While health inequities remain stark, removing financial or structural barriers to care does not necessarily improve uptake of life-saving treatment. Building on existing literature elaborating the sociocultural contexts that shape behaviours around pregnancy and childbirth can identify nuanced influences relating to pre-eclampsia care. METHODS: We conducted a cross-cultural comparative study exploring lived experiences and understanding of pre-eclampsia in Ethiopia, Haiti and Zimbabwe. Our primary objective was to examine what local understandings of pre-eclampsia might be shared between these three under-resourced settings despite their considerable sociocultural differences. Between August 2018 and January 2020, we conducted 89 in-depth interviews with individuals and 17 focus group discussions (n = 106). We purposively sampled perinatal women, survivors of pre-eclampsia, families of deceased women, partners, older male and female decision-makers, traditional birth attendants, religious and traditional healers, community health workers and facility-based health professionals. Template analysis was conducted to facilitate cross-country comparison drawing on Social Learning Theory and the Health Belief Model. RESULTS: Survivors of pre-eclampsia spoke of their uncertainty regarding symptoms and diagnosis. A lack of shared language challenged coherence in interpretations of illness related to pre-eclampsia. Across settings, raised blood pressure in pregnancy was often attributed to psychosocial distress and dietary factors, and eclampsia linked to spiritual manifestations. Pluralistic care was driven by attribution of causes, social norms and expectations relating to alternative care and trust in biomedicine across all three settings. Divergence across the contexts centred around nuances in religious or traditional practices relating to maternal health and pregnancy. CONCLUSIONS: Engaging faith and traditional caregivers and the wider community offers opportunities to move towards coherent conceptualisations of pre-eclampsia, and hence greater access to potentially life-saving care

A generative inference framework for analysing patterns of cultural change in sparse population data with evidence for fashion trends in LBK culture

Cultural change can be quantified by temporal changes in frequency of different cultural artefacts and it is a central question to identify what underlying cultural transmission processes could have caused the observed frequency changes. Observed changes, however, often describe the dynamics in samples of the population of artefacts, whereas transmission processes act on the whole population. Here we develop a modelling framework aimed at addressing this inference problem. To do so, we firstly generate population structures from which the observed sample could have been drawn randomly and then determine theoretical samples at a later time t2 produced under the assumption that changes in frequencies are caused by a specific transmission process. Thereby we also account for the potential effect of time-averaging processes in the generation of the observed sample. Subsequent statistical comparisons (e.g. using Bayesian inference) of the theoretical and observed samples at t2 can establish which processes could have produced the observed frequency data. In this way, we infer underlying transmission processes directly from available data without any equilibrium assumption. We apply this framework to a dataset describing pottery from settlements of some of the first farmers in Europe (the LBK culture) and conclude that the observed frequency dynamic of different types of decorated pottery is consistent with age-dependent selection, a preference for 'young' pottery types which is potentially indicative of fashion trends

The Diffusion of Humans and Cultures in the Course of the Spread of Farming

The most profound change in the relationship between humans and their environment was the introduction of agriculture and pastoralism. [....] For an understanding of the expansion process, it appears appropriate to apply a diffusive model. Broadly, these numerical modeling approaches can be catego- rized in correlative, continuous and discrete. Common to all approaches is the comparison to collections of radiocarbon data that show the apparent wave of advance of the transition to farming. However, these data sets differ in entry density and data quality. Often they disregard local and regional specifics and research gaps, or dating uncertainties. Thus, most of these data bases may only be used on a very general, broad scale. One of the pitfalls of using irregularly spaced or irregularly documented radiocarbon data becomes evident from the map generated by Fort (this volume, Chapter 16): while the general east-west and south-north trends become evident, some areas appear as having undergone anomalously early transitions to farming. This may be due to faulty entries into the data base or regional problems with radiocarbon dating, if not unnoticed or undocumented laboratory mistakes.Comment: 20 pages, 5 figures, submitted to Diffusive Spreading in Nature, Technology and Society, edited by Armin Bunde, J\"urgen Caro, J\"org K\"arger, Gero Vogl, Chapter 1

Experiences of maternity care among women at increased risk of preterm birth receiving midwifery continuity of care compared to women receiving standard care: Results from the POPPIE pilot trial.

BACKGROUND: Midwifery continuity of care models for women at low and mixed risk of complications have been shown to improve women's experiences of care. However, there is limited research on care experiences among women at increased risk of preterm birth. We aimed to explore the experiences of care among women with risk factors for preterm birth participating in a pilot trial (POPPIE) of a midwifery continuity of care model which included a specialist obstetric clinic. METHODS: A total of 334 pregnant women identified at increased risk of preterm birth were randomly allocated to either midwifery continuity of care (POPPIE group) or standard maternity care. Women in both groups were followed up at six-to-eight weeks postpartum and were invited to complete a postnatal survey either online or by post. An equal status exploratory sequential mixed method design was chosen to collect and analyse the quantitative postnatal survey data and qualitative interviews data. The postnatal survey included measures of social support, trust, perceptions of safety, quality of care, control during childbirth, bonding and quality of life. Categorical data were analysed with chi-squared tests and continuous data were analysed with t-tests and/or Mann-Whitney U test to measure differences in measures scores among groups. The qualitative interview data were subjected to a thematic framework analysis. Data triangulation brought quantitative and qualitative data together at the interpretation stage. FINDINGS: A total of 166 women completed the survey and 30 women were interviewed (90 and 16 in POPPIE group; 76 and 14 in standard group). We found survey respondents in the POPPIE group, compared to respondents in the standard group, were significantly more likely to report greater trust in midwives (Mann-Whitney U, p<0.0001), greater perceptions of safety during the antenatal care (t-test, p = 0.0138), have a particular midwife to contact when they needed during their pregnancy (t-test, p<0.0001) and the postnatal period (chi-squared, p<0.0001). They reported increased involvement in decisions regarding antenatal, intrapartum and postnatal care (t-test, p = 0.002; p = 0.008; p = 0.006 respectively); and greater postnatal support and advice about: feeding the baby (chi-squared, p<0.0001), handling, settling and looking after the baby (chi-squared, p<0.0001), baby's health and progress (chi-squared, p = 0.039), their own health and recovery (chi-squared, p = 0.006) and who to contact about any emotional changes (chi-squared, p = 0.005). There were no significant differences between groups in the reporting of perceptions of safety during birth and the postnatal period, concerns raised during labour and birth taken seriously, being left alone during childbirth at a time of worries, control during labour, bonding, social support, and physical and mental health related quality of life after birth. Results from qualitative interviews provided insight and depth into many of these findings, with women in the POPPIE group reporting more positive experiences of bonding towards their babies and more positive physical health postnatally. CONCLUSIONS: Compared with standard maternity care, women at increased risk of PTB who received midwifery continuity of care were more likely to report increased perceptions of trust, safety and quality of care. TRIAL REGISTRATION: ISRCTN (Number: 37733900); UK CRN (ID: 31951)

Multicenter cohort study, with a nested randomized comparison, to examine the cardiovascular impact of preterm preeclampsia

This study evaluated whether planned early delivery would ameliorate cardiovascular dysfunction six months postpartum, compared to usual care with expectant management, in women with late preterm preeclampsia. We conducted a mechanistic observational study in women with preterm preeclampsia between 34+0 and 36+6 weeks’ gestation, nested within a randomised controlled trial of planned early delivery versus expectant management (usual care), in 28 maternity hospitals in England and Wales. Women were followed up six months postpartum with cardiovascular assessments. The primary outcome was a composite of systolic and/or diastolic dysfunction (by 2009 and 2016 definitions of diastolic dysfunction). Between 27 April 2016 and 30 November 2018, 623 women were found to be eligible, of whom 420 (67%) were recruited. 133 women were randomised to planned delivery, 137 women were randomised to expectant management within the trial, while 150 women received expectant management outside of the trial. 321 (76.4%) completed their six month echocardiography assessment. 10% (31/321) had a left ventricular ejection fraction <55% whilst 71% (229/321) remained hypertensive. There were no differences in the primary outcome between the two randomised groups (planned delivery versus expectant management) using either the 2009 (RR 1.06; 95% CI 0.80, 1.40) or 2016 definitions (RR 0.78; 0.33, 1.86). In conclusion, we demonstrated that late preterm preeclampsia results in persistence of hypertension in the majority, and systolic LV dysfunction in 10%, of women six months postpartum. Planned early delivery does not affect these outcomes. Preeclampsia is not a self-limiting disease of pregnancy alone

Ripple oscillations in the left temporal neocortex are associated with impaired verbal episodic memory encoding

Background: We sought to determine if ripple oscillations (80-120Hz), detected in intracranial EEG (iEEG) recordings of epilepsy patients, correlate with an enhancement or disruption of verbal episodic memory encoding. Methods: We defined ripple and spike events in depth iEEG recordings during list learning in 107 patients with focal epilepsy. We used logistic regression models (LRMs) to investigate the relationship between the occurrence of ripple and spike events during word presentation and the odds of successful word recall following a distractor epoch, and included the seizure onset zone (SOZ) as a covariate in the LRMs. Results: We detected events during 58,312 word presentation trials from 7,630 unique electrode sites. The probability of ripple on spike (RonS) events was increased in the seizure onset zone (SOZ, p<0.04). In the left temporal neocortex RonS events during word presentation corresponded with a decrease in the odds ratio (OR) of successful recall, however this effect only met significance in the SOZ (OR of word recall 0.71, 95% CI: 0.59-0.85, n=158 events, adaptive Hochberg p<0.01). Ripple on oscillation events (RonO) that occurred in the left temporal neocortex non-SOZ also correlated with decreased odds of successful recall (OR 0.52, 95% CI: 0.34-0.80, n=140, adaptive Hochberg , p<0.01). Spikes and RonS that occurred during word presentation in the left middle temporal gyrus during word presentation correlated with the most significant decrease in the odds of successful recall, irrespective of the location of the SOZ (adaptive Hochberg, p<0.01). Conclusion: Ripples and spikes generated in left temporal neocortex are associated with impaired verbal episodic memory encoding

The acheulean handaxe : More like a bird's song than a beatles' tune?

© 2016 Wiley Periodicals, Inc. KV is supported by the Netherlands Organization for Scientific Research. MC is supported by the Canada Research Chairs Program, the Social Sciences and Humanities Research of Canada, the Canada Foundation for Innovation, the British Columbia Knowledge Development Fund, and Simon Fraser UniversityPeer reviewedPublisher PD

Signal peptide mutations in RANK prevent downstream activation of NF-κB

Familial expansile osteolysis and related disorders are caused by heterozygous tandem duplication mutations in the signal peptide region of the gene encoding receptor activator of NF-κB (RANK), a receptor critical for osteoclast formation and function. Previous studies have shown that overexpression of these mutant proteins causes constitutive activation of NF-κB signaling in vitro, and it has been assumed that this accounts for the focal osteolytic lesions that are seen in vivo. We show here that constitutive activation of NF-κB occurred in HEK293 cells overexpressing wild-type or mutant RANK but not in stably transfected cell lines expressing low levels of each RANK gene. Importantly, only cells expressing wild-type RANK demonstrated ligand-dependent activation of NF-κB. When overexpressed, mutant RANK did not localize to the plasma membrane but localized to extensive areas of organized smooth endoplasmic reticulum, whereas, as expected, wild-type RANK was detected at the plasma membrane and in the Golgi apparatus. This intracellular accumulation of the mutant proteins is probably the result of lack of signal peptide cleavage because, using two in vitro translation systems, we demonstrate that the mutations in RANK prevent cleavage of the signal peptide. In conclusion, signal peptide mutations lead to accumulation of RANK in the endoplasmic reticulum and prevent direct activation by RANK ligand. These results strongly suggest that the increased osteoclast formation/activity caused by these mutations cannot be explained by studying the homozygous phenotype alone but requires further detailed investigation of the heterozygous expression of the mutant RANK proteins. © 2011 American Society for Bone and Mineral Researc