Studies in Crystal Structures

This thesis embodies the results of investigations into two dissimilar aspects of X-ray crystallography, hence the rather general title "Studies in Crystal Structure." The first part concerns a study of the crystal structure of Tris (methylsulphonyl) methane, a somewhat unusual organic compound, which is an acid of strength comparable with hydrochloric acid. Two aspects of this structure re of interest, firstly the molecular geometry, because of theoretical speculation previous to the work, and secondly the fact that the crystals give rise to an unusual form of diffuse scattering of X-rays. That the two aspects are not independent was shown in the course of the investigation. It was impossible to account for the intensities of the Bragg reflexions on a basis of any ordered structure. These intensities can only refer to structure which is an average taken over the whole crystal and the nature of this 'average structure' was deduced, a ter much work in two dimensions, by the use of three-dimensional data and vector and Fourier methods. The average structure involves partial occupancy of sites in the unitcell whose positions are related by a centre of symmetry, not required by the space-group. The two sites do not appear to be occupied equally. The results of a least-squares refinement of the average structure are given. The residual is 9% and thus the molecular structure is known to a fair degree of accuracy. The structure appears to contradict the previously mentioned theoretical ideas. The bond lengths and angles are comparable with those in similar compounds. The nature of the average structure has been used as a starting point for investigations of the disorder with the help of on optical diffractometer. Details are given of the finding of a fairly small unit which gives rise to an optical transform similar to the X-ray photographs. The extension of this model to the whole crystal is also considered. The second part of the thesis concerns work in a more conventional field of crystal chemistry; that of alkaloid structure. Details are given of the investigation of the crystal structure of the alkaloid Calycanthine, derived from the poisonous shrub, Calycanthus aureus. The structure of this compound as known only partially at the start of the work. The structure was studied initially by two-dimensional methods and, while partial success in the Location of the atoms in the crystals of the hydro- bromide of the alkaloid was attained by the method of 'generalized projections', the crystal structure was not solved completely until three-dimensional act mods, using the 'heavy-atom' technique, were employed

Offset-variable density improves acoustic full-waveform inversion: a shallow marine case study

We have previously applied three-dimensional acoustic, anisotropic, full-waveform inversion to a shallow-water, wide-angle, ocean-bottom-cable dataset to obtain a high-resolution velocity model. This velocity model produced: an improved match between synthetic and field data, better flattening of common-image gathers, a closer fit to well logs, and an improvement in the pre-stack depth- migrated image. Nevertheless, close examination reveals that there is a systematic mismatch between the observed and predicted data from this full-waveform inversion model, with the predicted data being consistently delayed in time. We demonstrate that this mismatch cannot be produced by systematic errors in the starting model, by errors in the assumed source wavelet, by incomplete convergence, or by the use of an insufficiently fine finite-difference mesh. Throughout these tests, the mismatch is remarkably robust with the significant exception that we do not see an analogous mismatch when inverting synthetic acoustic data. We suspect therefore that the mismatch arises because of inadequacies in the physics that are used during inversion. For ocean-bottom-cable data in shallow water at low frequency, apparent observed arrival times, in wide-angle turning-ray data, result from the characteristics of the detailed interference pattern between primary refractions, surface ghosts, and a large suite of wide-angle multiple reflected and/or multiple refracted arrivals. In these circumstances, the dynamics of individual arrivals can strongly influence the apparent arrival times of the resultant compound waveforms. In acoustic full-waveform inversion, we do not normally know the density of the seabed, and we do not properly account for finite shear velocity, finite attenuation, and fine-scale anisotropy variation, all of which can influence the relative amplitudes of different interfering arrivals, which in their turn influence the apparent kinematics. Here, we demonstrate that the introduction of a non-physical, offset-variable, water density during acoustic full-waveform inversion of this ocean- bottom-cable field dataset, can compensate efficiently and heuristically for these inaccuracies. This approach improves the travel-time match, and consequently increases both the accuracy and resolution of the final velocity model that is obtained using purely acoustic full-waveform inversion at minimal additional cost

Time Course of Recruitment, Pit Formation and Apoptosis of Osteoclast Populations on Dentin In Vitro

The resorptive capacity of osteoclasts in vitro has been used as an indicator of bone resorption. However, the kinetics of osteoclast development and senescence is not well understood. It has been noted that mononuclear precursors migrate to calcified substrate and after multi-nucleation become competent bone resorbing cells. Osteoclasts, once finished a wave of resorption, become senescent. In order to determine the survival characteristics of osteoclast populations involved in calcified tissue destruction, we have investigated the time course of the recruitment to dentin and apoptosis of osteoclasts. We have established the linkage between these measurements and the time course of the appearance of pits using both chick and rat osteoclasts in vitro. Osteoclasts from both species caused increases in pit number associated with decreases in cell number on dentin. In the rat model, we have used a fluorescent linker to mark cells before they migrate to dentin and have shown that cells can be followed from the culture dish onto the dentin disc. In the chick model, we have used time lapse cinematography and fluorescent nuclear staining to observe death of osteoclasts on dentin and have established an osteoclast half live in vitro

The Birthplace in England national prospective cohort study: further analyses to enhance policy and service delivery decision-making for planned place of birth

Background: Evidence from the Birthplace in England Research Programme supported a policy of offering ‘low risk’ women a choice of birth setting, but a number of unanswered questions remained. Aims: This project aimed to provide further evidence to support the development and delivery of maternity services and inform women’s choice of birth setting: specifically, to explore maternal and organisational factors associated with intervention, transfer and other outcomes in each birth setting in ‘low risk’ and ‘higher risk’ women. Design: Five component studies using secondary analysis of the Birthplace prospective cohort study (studies 2–5) and ecological analysis of unit/NHS trust-level data (studies 1 and 5). Setting: Obstetric units (OUs), alongside midwifery units (AMUs), freestanding midwifery units (FMUs) and planned home births in England. Participants: Studies 1–4 focused on ‘low risk’ women with ‘term’ pregnancies planning vaginal birth in 43 AMUs (n = 16,573), in 53 FMUs (n = 11,210), at home in 147 NHS trusts (n = 16,632) and in a stratified, random sample of 36 OUs (n = 19,379) in 2008–10. Study 5 focused on women with pre-existing medical and obstetric risk factors (‘higher risk’ women). Main outcome measures: Interventions (instrumental delivery, intrapartum caesarean section), a measure of low intervention (‘normal birth’), a measure of spontaneous vaginal birth without complications (‘straightforward birth’), transfer during labour and a composite measure of adverse perinatal outcome (‘intrapartum-related mortality and morbidity’ or neonatal admission within 48 hours for > 48 hours). In studies 1 and 3, rates of intervention/maternal outcome and transfer were adjusted for maternal characteristics. Analysis: We used (a) funnel plots to explore variation in rates of intervention/maternal outcome and transfer between units/trusts, (b) simple, weighted linear regression to evaluate associations between unit/trust characteristics and rates of intervention/maternal outcome and transfer, (c) multivariable Poisson regression to evaluate associations between planned place of birth, maternal characteristics and study outcomes, and (d) logistic regression to investigate associations between time of day/day of the week and study outcomes. Results: Study 1 – unit-/trust-level variations in rates of interventions, transfer and maternal outcomes were not explained by differences in maternal characteristics. The magnitude of identified associations between unit/trust characteristics and intervention, transfer and outcome rates was generally small, but some aspects of configuration were associated with rates of transfer and intervention. Study 2 – ‘low risk’ women planning non-OU birth had a reduced risk of intervention irrespective of ethnicity or area deprivation score. In nulliparous women planning non-OU birth the risk of intervention increased with increasing age, but women of all ages planning non-OU birth experienced a reduced risk of intervention. Study 3 – parity, maternal age, gestational age and ‘complicating conditions’ identified at the start of care in labour were independently associated with variation in the risk of transfer in ‘low risk’ women planning non-OU birth. Transfers did not vary by time of day/day of the week in any meaningful way. The duration of transfer from planned FMU and home births was around 50–60 minutes; transfers for ‘potentially urgent’ reasons were quicker than transfers for ‘non-urgent’ reasons. Study 4 – the occurrence of some interventions varied by time of the day/day of the week in ‘low risk’ women planning OU birth. Study 5 – ‘higher risk’ women planning birth in a non-OU setting had fewer risk factors than ‘higher risk’ women planning OU birth and these risk factors were different. Compared with ‘low risk’ women planning home birth, ‘higher risk’ women planning home birth had a significantly increased risk of our composite adverse perinatal outcome measure. However, in ‘higher risk’ women, the risk of this outcome was lower in planned home births than in planned OU births, even after adjustment for clinical risk factors. Conclusions: Expansion in the capacity of non-OU intrapartum care could reduce intervention rates in ‘low risk’ women, and the benefits of midwifery-led intrapartum care apply to all ‘low risk’ women irrespective of age, ethnicity or area deprivation score. Intervention rates differ considerably between units, however, for reasons that are not understood. The impact of major changes in the configuration of maternity care on outcomes should be monitored and evaluated. The impact of non-clinical factors, including labour ward practices, staffing and skill mix and women’s preferences and expectations, on intervention requires further investigation. All women planning non-OU birth should be informed of their chances of transfer and, in particular, older nulliparous women and those more than 1 week past their due date should be advised of their increased chances of transfer. No change in the guidance on planning place of birth for ‘higher risk’ women is recommended, but research is required to evaluate the safety of planned AMU birth for women with selected relatively common risk factors. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Perinatal and maternal outcomes in planned home and obstetric unit births in women at ‘higher risk’ of complications: secondary analysis of the Birthplace national prospective cohort study

Objective: To explore and compare perinatal and maternal outcomes in women at ‘higher risk’ of complications planning home versus obstetric unit (OU) birth. Design: Prospective cohort study. Setting: OUs and planned home births in England. Population: 8180 ‘higher risk’ women in the Birthplace cohort. Methods: We used Poisson regression to calculate relative risks adjusted for maternal characteristics. Sensitivity analyses explored possible effects of differences in risk between groups and alternative outcome measures. Main outcome measures: Composite perinatal outcome measure encompassing ‘intrapartum related mortality and morbidity’ (intrapartum stillbirth, early neonatal death, neonatal encephalopathy, meconium aspiration syndrome, brachial plexus injury, fractured humerus or clavicle) and neonatal admission within 48 hours for more than 48 hours. Two composite maternal outcome measures capturing intrapartum interventions/adverse maternal outcomes and straightforward birth. Results: The risk of ‘intrapartum related mortality and morbidity’ or neonatal admission for more than 48 hours was lower in planned home births than planned OU births [adjusted relative risks (RR) 0.50, 95% CI 0.31–0.81]. Adjustment for clinical risk factors did not materially affect this finding. The direction of effect was reversed for the more restricted outcome measure ‘intrapartum related mortality and morbidity’ (RR adjusted for parity 1.92, 95% CI 0.97–3.80). Maternal interventions were lower in planned home births. Conclusions: The babies of ‘higher risk’ women who plan birth in an OU appear more likely to be admitted to neonatal care than those whose mothers plan birth at home, but it is unclear if this reflects a real difference in morbidity. Rates of intrapartum related morbidity and mortality did not differ statistically significantly between settings at the 5% level but a larger study would be required to rule out a clinically important difference between the groups

Mindfulness-based cognitive therapy (MBCT) reduces the association between depressive symptoms and suicidal cognitions in patients with a history of suicidal depression.

Objective: In patients with a history of suicidal depression, recurrence of depressive symptoms can easily reactivate suicidal thinking. In this study, we investigated whether training in mindfulness, which is aimed at helping patients “decenter” from negative thinking, could help weaken the link between depressive symptoms and suicidal cognitions. Method: Analyses were based on data from a recent randomized controlled trial, in which previously suicidal patients were allocated to mindfulness-based cognitive therapy (MBCT), an active control treatment, cognitive psychoeducation (CPE), which did not include any meditation practice, or treatment as usual (TAU). After the end of the treatment phase, we compared the associations between depressive symptoms, as assessed through self-reports on the Beck Depression Inventory–II (Beck, Steer, & Brown, 1996), and suicidal thinking, as assessed through the Suicidal Cognitions Scale (Rudd et al., 2001). Results: In patients with minimal to moderate symptoms at the time of assessment, comparisons of the correlations between depressive symptoms and suicidal cognitions showed significant differences between the groups. Although suicidal cognitions were significantly related to levels of symptoms in the 2 control groups, there was no such relation in the MBCT group. Conclusion: The findings suggest that, in patients with a history of suicidal depression, training in mindfulness can help to weaken the association between depressive symptoms and suicidal thinking, and thus reduce an important vulnerability for relapse to suicidal depression

The OASI care bundle quality improvement project: lessons learned and future direction.

Rising rates of obstetric anal sphincter injury (OASI) led to a collaborative effort by the Royal College of Obstetricians and Gynaecologists (RCOG) and the Royal College of Midwives (RCM) to develop and evaluate the OASI Care Bundle (OASI-CB). The OASI-CB comprises four practices (antenatal discussion about OASI, manual perineal protection, mediolateral episiotomy at 60° from the midline, and systematic examination of the perineum, vagina and ano-rectum after vaginal birth) and was initially implemented as part of a quality improvement (QI) project-"OASI1"-in 16 maternity units across Great Britain. Evaluation of the OASI1 project found that the care bundle reduced OASI rates and identified several barriers and enablers to implementation. This paper summarises the key findings, including strengths, limitations and lessons learned from the OASI1 QI project, and provides rationale for further evaluation of the OASI-CB