Breech specialist midwives and clinics in the OptiBreech Trial feasibility study: An implementation process evaluation.

BACKGROUND: Attendance of skilled and experienced professionals at breech births has been associated with a reduction in adverse perinatal outcomes. We aimed to determine whether United Kingdom National Health Service (NHS) sites could reliably provide attendants with OptiBreech training and/or advanced proficiency (intervention feasibility) and consistent care (fidelity) that meets women's needs (acceptability), with low neonatal admission rates (safety) and recruitment adequate to support a clinical trial (trial feasibility). METHODS: Mixed methods implementation evaluation was used. Settings were 13 services in England and Wales. Participants were 82 women requesting support for a vaginal breech birth (VBB) at term. Outcomes were descriptively analyzed. Twenty-one women were interviewed, and transcripts were analyzed using the Theoretical Framework of Acceptability. Iterative analysis informed subsequent interviews and the ongoing process of implementation across sites. RESULTS: Although we initially suggested multidisciplinary teams, actively recruiting Trusts yielded services where VBB care was provided through a dedicated clinic, organized and delivered primarily by a lead midwife who functioned as a specialist. This model achieved 87.5% fidelity with the intervention's goal of ensuring the attendance of OptiBreech-trained professionals. Neonatal outcomes remained stable, with an admission rate of 5.5%. Women reported care from specialist midwives as highly acceptable, but the model is vulnerable without a strategic effort to develop additional proficient team members. CONCLUSIONS: Dedicated clinics coordinated by specialist midwives appear to be an acceptable and feasible implementation strategy to test the safety and effectiveness of proficient team care for VBB in a clinical trial. Back-up arrangements should be maintained while additional members of the team develop proficiency.

Toroidal nuclei of columnar lyotropic chromonic liquid crystals coexisting with an isotropic phase.

Nuclei of ordered materials emerging from the isotropic state usually show a shape topologically equivalent to a sphere; the well-known examples are crystals and nematic liquid crystal droplets. In this work, we explore experimentally and theoretically the toroidal in shape nuclei of columnar lyotropic chromonic liquid crystals coexisting with the isotropic phase. The geometry of these toroids depends strongly on concentrations of the disodium cromoglycate (DSCG) and the crowding agent, polyethylene glycol (PEG). High concentrations of DSCG and PEG result in thick toroids with small central holes, while low concentrations yield thin toroids with wide holes. The multitude of the observed shapes is explained by the balance of bending elasticity and anisotropic interfacial tension.

Ion-dependent DNA configuration in bacteriophage capsids.

Bacteriophages densely pack their long double-stranded DNA genome inside a protein capsid. The conformation of the viral genome inside the capsid is consistent with a hexagonal liquid crystalline structure. Experiments have confirmed that the details of the hexagonal packing depend on the electrochemistry of the capsid and its environment. In this work, we propose a biophysical model that quantifies the relationship between DNA configurations inside bacteriophage capsids and the types and concentrations of ions present in a biological system. We introduce an expression for the free energy that combines the electrostatic energy with contributions from bending of individual segments of DNA and Lennard-Jones-type interactions between these segments. The equilibrium points of this energy solve a partial differential equation that defines the distributions of DNA and the ions inside the capsid. We develop a computational approach that allows us to simulate much larger systems than what is possible using the existing molecular-level methods. In particular, we are able to estimate bending and repulsion between the DNA segments as well as the full electrochemistry of the solution, both inside and outside of the capsid. The numerical results show good agreement with existing experiments and with molecular dynamics simulations for small capsids.

Physiological breech birth training: An evaluation of clinical practice changes after a one-day training program.

BACKGROUND: The "physiological breech birth" one-day training program is based on evidence about the physiology of breech births and how clinicians learn breech skills. Previous evaluations have demonstrated positive effects on confidence and knowledge, but the training's effect on clinical practice and outcomes is unknown. METHODS: A mixed-methods evaluation was conducted in eight National Health Service hospitals in England and Northern Ireland. Changes in confidence and knowledge were assessed using pretraining and post-training surveys. Mode of birth and maternal birth positions were evaluated using audit data covering one year before the training and one year after, for all singleton vaginal breech births at term. FINDINGS: A total of 263 participants completed the surveys. Confidence in managing breech births in both upright and supine positions significantly increased, as did participant knowledge. Audited data for 1402 women were collected. Overall vaginal birth rates remained similar in both periods. Among singleton vaginal breech births >37 weeks, the use of upright birthing positions increased significantly (P = .002). The study was not powered to detect differences in other outcomes, but pilot data were collected to inform the design of future studies. CONCLUSIONS: Increase in use of upright birthing positions suggests that physiological breech birth training is likely to lead to clinical practice changes, which may help support maternal choice in line with current guidance. However, provision of a one-day training program did not change overall vaginal breech birth rates. Adequately powered research is needed to determine effects of clinical practice changes on clinical outcomes.

Face-to-pubes rotational maneuver for bilateral nuchal arms in a vaginal breech birth, resolved in an upright maternal position: A case report.

BACKGROUND: A physiological breech birth is one in which the woman is encouraged to remain active throughout her labor and able to assume the position of her choice for the birth. Use of this strategy within the United Kingdom National Health Service has led to the use of innovative maneuvers to relieve obstruction when women give birth in upright positions, for example, kneeling or standing. This includes use of the face-to-pubes rotational maneuver to relieve extended nuchal arm(s). In this paper, we report a case where the face-to-pubes rotational maneuver was used to relieve bilateral nuchal arm entrapment in a breech birth. METHODS: Single-case study. We aimed to generate an in-depth understanding of how this maneuver works and how professionals decide to use it by exploring its use in a real-life context. RESULTS: The face-to-pubes rotational maneuver appears to be an effective method of relieving nuchal arm entrapment when used by experienced hands. In cases of bilateral nuchal arm entrapment, elevation to a higher station may be necessary to dis-impact the arms above the pelvic inlet before the fetus can be rotated. After face-to-pubes rotation and release of arms, the head should be realigned in an occiput anterior position for delivery. CONCLUSION: The face-to-pubes rotational maneuver can be taught for resolution of nuchal arms in an upright position. Parents should be informed of the availability or not of a specialist midwife trained in physiological breech birth, as this may be important to their decision-making.

Practical insight into upright breech birth from birth videos: A structured analysis.

BACKGROUND: We aimed to identify common features of upright vaginal breech births with good outcomes to refine a physiological approach to teaching breech birth. METHODS: We performed a structured analysis of 42 videos of successful upright breech births (eg, kneeling, hand/knees), facilitated by obstetricians (n = 34) and midwives (n = 8) in nine different countries. Precise timings and relevant clinical details were recorded on an Excel spreadsheet. Each video was analyzed twice by at least two members of the research team. Time-to-event intervals, frequencies of interventions, and descriptive statistics were calculated using SPSS. RESULTS: A completely spontaneous (labor mechanisms and maternal effort only) birth occurred in 14/42 (33%) cases. The median time between the birth of the fetal pelvis and the head in all births was 1:52 (IQR 1:05,2:46; min:sec). Lack of spontaneous rotation to a sacro-anterior position by the time the fetus had emerged to the nipple line was strongly associated with fetal arm entrapment. The following maneuvers were used: shoulder press to flex the aftercoming head in midpelvis or outlet (n = 24), sweeping down arm/s (n = 12), buttock lift to assist shoulder press (n = 6), modified Mauriceau (n = 6), rotational maneuvers to release an entrapped arm (n = 6), elevate and rotate fetal head to assist engagement (n = 2), and conversion into supine maternal position (n = 2). CONCLUSIONS: Most upright breech births occur within 3 minutes of the birth of the fetal pelvis. Upright breech birth attendants use variations of traditional maneuvers. We introduce a physiological breech algorithm as an initial timekeeping framework for teaching, research, and practice.

Molecular Complexity as a Driver for Chemical Process Innovation in the Pharmaceutical Industry.

A Perspective of our work in the development of innovative synthetic methods within the discipline of Process Research and Development is presented. Through an overview of some of the programs that we have worked on during the past decade, we have selected cases studies to illustrate the challenges faced in development of robust chemical processes for molecules on a multi-kilogram scale. The examples have been selected to demonstrate the innovative chemistry being developed within our laboratories with a focus on fragment design, asymmetric synthesis, new synthetic reagents, and the methods that have allowed us to deliver cost-effective syntheses under reduced timelines in an increasingly competitive environment. The technical challenges are presented in the context of molecule complexity that while increasing in the portfolio of small molecules being developed inspires us to deliver new solutions. Overall, our goal is to highlight the exciting work that can be done within our field to support the discovery and delivery of medicines to patients.

Development of a Commercial Process To Prepare AMG 232 Using a Green Ozonolysis-Pinnick Tandem Transformation.

A robust process to manufacture AMG 232 was developed to deliver drug substance of high purity. Highlights of the commercial process development efforts include the following: (i) use of a novel bench-stable Vilsmeier reagent, methoxymethylene- N, N-dimethyliminium methyl sulfate, for selective in situ activation of a primary alcohol intermediate; (ii) use of a new crystalline and stable isopropyl calcium sulfinate reagent ensuring robust preparation of a sulfone intermediate; (iii) development of a safe ozonolysis process conducted in an aqueous solvent mixture in either batch or continuous manufacturing mode; and (iv) control of the drug substance purity by crystallization of a salt rejecting impurities effectively. The new process was demonstrated to afford the drug substance (99.9 LC area %) in 49.8% overall yield from starting material DLAC (1).

Expertise in physiological breech birth: A mixed-methods study.

BACKGROUND: The safety of vaginal breech birth depends on the expertise of birth attendants, yet the meaning of "expertise" remains unclear and subjectively defined. The objective of this study was to define expertise and the roles experts may play in expanding access to this service. METHODS: We performed an integrative analysis of two strands of data concerning expertise in physiological breech birth, including the following: survey data from a Delphi study involving 26 very experienced clinicians (mean experience = 135 breech births) and 2 service user representatives, and interviews from a grounded theory study of 14 clinicians more moderately experienced with physiological methods (5-30 upright breech births). Data were pooled and analyzed using constant comparative methods. RESULTS: Expertise is defined by its ongoing function, the generation of comparatively good outcomes, and confidence and competence among colleagues. Although clinical experience is important, expertise is developed and expressed in social clinical roles, which expand as experience grows: clinician, mentor, specialist, and expert. To develop expertise within a service, clinicians who have an interest in breech birth should be supported to perform these roles within specialist teams. CONCLUSIONS: Specialist breech teams may facilitate the development of expertise within maternity care settings. Evaluation of expertise based on enablement of women and colleagues, as well as outcomes, will potentially avoid the pitfalls of alienation produced by some forms of specialist authority.

Effectiveness of vaginal breech birth training strategies: An integrative review of the literature.

BACKGROUND: The safety of vaginal breech birth depends on the skill of the attendant. The objective of this review was to identify, synthesize, and report the findings of evaluated breech birth training strategies. METHODS: A systematic search of the following on-line databases: Medline, CINAHL Plus, PsychINFO, EBM Reviews/Cochrane Library, EMBASE, Maternity and Infant Care, and Pubmed, using a structured search strategy. Studies were included in the review if they evaluated the efficacy of a breech birth training program or particular strategies, including obstetric emergency training evaluations that reported differentiated outcomes for breech. Out of 1040 original citings, 303 full-text articles were assessed for eligibility, and 17 methodologically diverse studies met the inclusion criteria. A data collection form was used to extract relevant information. Data were synthesized, using an evaluation levels framework, including reaction, learning (subjective and objective assessment), and behavioral change. RESULTS: No evaluations included clinical outcome data. Improvements in self-assessed skill and confidence were not associated with improvements in objective assessments or behavioral change. Inclusion of breech birth as part of an obstetric emergencies training package without support in practice was negatively associated with subsequent attendance at vaginal breech births. CONCLUSIONS: As a result of the heterogeneity of the studies available, and the lack of evidence concerning neonatal or maternal outcomes, no conclusive practice recommendations can be made. However, the studies reviewed suggest that vaginal breech birth training may be enhanced by reflection, repetition, and experienced clinical support in practice. Further evaluation studies should prioritize clinical outcome data.

Physiological breech birth. Evaluation of a training programme for birth professionals.

This article evaluates the results of physiological breech birth (PBB) study days provided by breech Birth Network (BBN). An expanded version of this article, with further details including the statistics and additional information about the content of the training, is available on our website. This paper reports an evaluation of the BBN PBB training programme, which has been developed out of consensus research, with highly experienced health professionals. The training was delivered in four National Health Service trust hospitals in the north and south of England throughout the spring and summer of 2016. The evaluation involved pre- and post-training surverys containing a mixture of open-ended and multiple-choice questions, and rating scales. Data were analysed descriptively. The results indicated that the training addressed the concernsof the participants and was rated highly in expected usefulness for practice. Significant improvements in self-reported confidence and objectively assessed knowledge were observed. Participants found discussions and hands-on practice accompanying videos helpful, and reported concerns about lack of support and involvement of obstetric colleagues both before and after the training. The package is an effectively designed and replicable programme for introducing PBB practice to health care professionals.

Unexpected breech: what can midwives do?

Approximately 1:100-150 women at term experience diagnosis of breech presentation for the first time in labour (Walker 2013). Such an unanticipated discovery is stressful for both women and the healthcare professionals who care for them. Undiagnosed breech experiences can leave midwives and women elated, distressed or disempowered. This article suggests practical ways midwifery change leaders can improve care for undiagnosed breeches within organisations: plan or scan antenatally, and identify a multi-disciplinary breech leadership team for support, reflection and collaborative professional development.

Optimization of chiral structures for microscale propulsion.

Recent advances in micro- and nanoscale fabrication techniques allow for the construction of rigid, helically shaped microswimmers that can be actuated using applied magnetic fields. These swimmers represent the first steps toward the development of microrobots for targeted drug delivery and minimally invasive surgical procedures. To assess the performance of these devices and improve on their design, we perform shape optimization computations to determine swimmer geometries that maximize speed in the direction of a given applied magnetic torque. We directly assess aspects of swimmer shapes that have been developed in previous experimental studies, including helical propellers with elongated cross sections and attached payloads. From these optimizations, we identify key improvements to existing designs that result in swimming speeds that are 70-470% of their original values.

To ECV or not to ECV? The current evidence base concerning external cephalic version.

External cephalic version (ECV) is the technique of attempting to turn a baby in the womb from a head-up to a head-down position. The practice is grounded on evidence that vaginal breech birth (VBB) presents greater short-term risks for babies than caesarean section (CS) (Hofmeyr et al 2011), but that labour and vaginal birth also offer benefits to both mothers and babies. Therefore, if we can turn babies to a head-down position, we can reduce the risks associated with both VBB and CS, and enable mother and baby to benefit from labour and birth.

Variations of cervical head entrapment in vaginal breech births: New insights on how to prevent, manage and resolve.

This paper presents a novel, systematic way to understand the causes of cervical head entrapment in vaginal breech births, and new insights into management. Three different types of cervical head entrapment are described, with detailed illustrations: unpredictable and potentially catastrophic, manageable, and preventable. The first affects preterm and growth-restricted fetuses. The second involves some degree of uterine prolapse. The third may result from prolonged head entrapment at the pelvic inlet, leaving time for cervical contraction or oedematous entrapment. Traditional and innovative strategies to resolve and prevent this complication are described and illustrated, with suggestions for further research.

Barriers and facilitators for implementation of OptiBreech collaborative care: A qualitative study as part of an implementation process evaluation.

PROBLEM: Lack of opportunity for breech training and clinical experience reduced professional confidence and expertise in supporting vaginal breech birth. BACKGROUND: OptiBreech collaborative care is a care pathway for breech presentation at term that aims to enable improve safety through person-centred care and improved training opportunities for maternity professionals, within dedicated clinics and intrapartum support. In feasibility work, barriers and facilitators to team implementation were observed by team members. AIM: This study sought to describe factors affecting optimal future implementation and safety of OptiBreech care. METHODS: Semi-structured interviews were conducted with staff members at 13 OptiBreech trial sites (17 midwives and 4 obstetricians, n=21), via video conferencing software. The Theoretical Domains Framework (TDF) was used to identify factors impacting team implementation. Themes identified in the TDF were refined in reflexive discussion and grouped into key facilitators, key barriers, and dynamic factors (which span both barriers and facilitators). The interviews were then coded, analysed, and interpreted according to the refined framework. FINDINGS: The key facilitators were broadly categorised within skill development, beliefs about capabilities, and social support from the wider multidisciplinary team. Key barrier categories were resources, social obstacles, and fears about consequences. Dynamic factor categories were individual responsibility, training, and attending births. CONCLUSION: While some factors affecting implementation were specific to the individuals and cultures of certain Trusts, recommendations emerged from analysis that are more widely applicable across multiple settings. These should be considered going forward for future service implementation, and in the next stage of OptiBreech clinical trials.

Structural Elucidation and Absolute Stereochemistry for Pharma Compounds Using MicroED.

Microcrystal electron diffraction (microED) is an emerging technique for rapid crystallographic analysis of small molecule micro- and nanocrystals. In this report, we evaluate the applicability of microED to pharmaceutical compounds through the analysis of 30 samples obtained from the process and medicinal chemistry groups at Amgen Inc. Using only 40 h of microscope time, 15 of 30 crystal structures were elucidated. From these crystal structures, all chiral compounds had the correct absolute stereochemistry assigned by dynamical refinement of continuous rotation electron diffraction data, confirming dynamical refinement as a promising tool for the absolute stereochemistry determination of pharmaceutically relevant compounds.

Not too fast, not too slow: A review of historical trends in vaginal breech time management.

PROBLEM: A lack of consistent professional guidance on when to intervene during emergence (buttocks and anus visible at the introitus to birth of the head) in vaginal breech birth (VBB). BACKGROUND: Hypoxia and asphyxia are common complications of VBB, especially due to umbilical cord compression around the time of emergence. AIM: To gain insight into VBB time management trends, the evidence behind these practices and how they may have influenced outcomes. METHODS: Literature review of obstetric textbooks published between 1960 and 2000 contained in the Wellcome Collection and Royal College of Obstetricians and Gynaecologists Library in London. FINDINGS: 90 textbooks were reviewed. Recommendations for 'safe' intervals between birth of the umbilicus and the head ranged from 5 to 20 min. Many sources focused only on the time required to deliver the head, with 'up to 10 min' being the most common interval described. The review found no mention of cord compression causing concern earlier in breech births than once the umbilicus itself is delivered, nor any evidence to support the recommendations. DISCUSSION: These findings demonstrate a long-term pattern across the second half of the 20th century, whereby birth attendants were urged not to rush emergence nor delay intervention but were given little clear guidance on optimal timings. CONCLUSION: Clear, evidence-based guidance should be provided in breech training materials to avoid unnecessary hypoxic injuries, and this guidance should be rigorously evaluated.