Using routinely collected data to evaluate the performance and quality of English NHS maternity services

This ‘publication style’ thesis comprises a collection of research papers, each of which seeks to address a different element of the overall aim: to determine the extent to which electronic data, captured routinely as part of clinical care and hospital administration, can be used to evaluate the performance and quality of English NHS maternity services. These routine data sources present opportunities for research groups to examine whether current practice and outcomes in NHS maternity services meet guidelines and standards, and to guide research and initiatives to improve the quality of maternity care at a regional and national level. However, the difficulty faced by clinicians, managers and service users in interpreting some of the currently available maternity statistics highlights the need to improve the usefulness of the information being produced to evaluate NHS maternity services. The first part of this thesis comprises a review of the advantages and limitations of existing routinely collected data sources for these purposes. The review identifies three key challenges relating to 1) the handling of missing or inconsistent information, 2) the definition of key exposure, outcome and confounding variables relevant to maternity care and 3) adjustment for confounding variables. In the second part, novel techniques are developed to address current weaknesses in the secondary analysis of these data. The findings show that these new methods can be used to derive accurate information on two key data items: 1) the method of delivery and 2) the parity status of women, although misclassification rates are higher for some subgroups of women. This section demonstrates that overall the quality of administrative data is sufficient to support the evaluation of maternity care but that some organisational-level statistics are sensitive to inconsistencies in the data. Consequently, it is recommended that publications of quality indicators should describe how data were prepared and analysed, in order for results to be replicable. In the third part, a series of retrospective cohort studies are described that illustrate how these new methodological techniques can be used to overcome the three challenges identified in the part 1. The first study calculated rates of attempted and successful vaginal birth after caesarean section, which had not previously been done using administrative data at national and provider-level basis (Chapter 6), and found that among women who attempted a trial of labour for their second birth, almost two-thirds successfully achieved a vaginal delivery. A second study evaluated a clinical intervention (induction of labour) designed to prevent rare outcomes such as perinatal mortality which are impractical to investigate by experimental methods (Chapter 7); it found that bringing forward the routine offer of induction of labour from the current recommendation of 41±42 weeks to 40 weeks of gestation in nulliparous women aged >=35 years might reduce overall rates of perinatal death. A third study examined an important health policy question about when staff should be present on the labour ward (Chapter 8) and involved the linkage of administrative, staffing and clinical datasets. The study found no difference in the rate of maternal and neonatal morbidity according to the presence of consultants on the labour ward. A final study examined whether administrative data provided a cost effective way of monitoring perinatal outcomes using a composite indicator of adverse outcomes. The study found that a measure developed in Australia could be adapted to English data, and had good concurrent and predictive ability (Chapter 9). The thesis concludes that hospital administrative datasets, linked with other sources of clinical data where necessary, are a valuable resource for population-based service evaluations. Taken together, the novel techniques developed, validated and applied as part of this programme of work, advance our understanding of the ways in which routinely collected maternity data can and cannot be used to support the evaluation of maternity services. Whilst these data are not perfect and there is certainly a need to improve their completeness and consistency, this research demonstrates that it is possible to develop techniques to identify and manage data errors, and methods to clearly define key exposure, outcome and confounding variables. Together, these allow answers to be found to many potential questions about maternity care

Improved monitoring of oriental fruit moth (Lepidoptera: Tortricidae) with terpinyl acetate plus acetic acid membrane lures

Male and female moth catches of Grapholita molesta (Busck) in traps were evaluated in stone and pome fruit orchards untreated or treated with sex pheromones for mating disruption in Uruguay, Argentina, Chile, USA, and Italy from 2015 to 2017. Trials evaluated various blends loaded into either membrane cup lures or septa. Membrane lures were loaded with terpinyl acetate (TA), acetic acid (AA) and (Z)‐3‐hexenyl acetate alone or in combinations. Two septa lures were loaded with either the three‐component sex pheromone blend for G. molesta alone or in combination with codlemone (2‐PH), the sex pheromone of Cydia pomonella (L). A third septum lure included the combination sex pheromone blend plus pear ester, (E,Z)‐2,4‐ethyl decadienoate (2‐PH/PE), and a fourth septum was loaded with only β‐ocimene. Results were consistent across geographical areas showing that the addition of β‐ocimene or (Z)‐3‐hexenyl acetate did not increase moth catches. The addition of pear ester to the sex pheromone lure marginally increased moth catches. The use of TA and AA together significantly increased moth catches compared with the use of only one of the two components. Traps with the TA/AA lure outperformed the Ajar trap baited with a liquid TA plus sugar bait. The emission rate of AA was not a significant factor affecting the performance of the TA/AA lure. The addition of TA/AA significantly increased moth catches when combined with the 2‐PH lure. The TA/AA lure also allowed traps to catch both sexes. Catch of C. pomonella with the 2‐PH lure was comparable to the use of codlemone; however, moth catch was significantly reduced with the 2‐PH/PE lure. Optimization of these complex lures can likely further improve managers’ ability to monitor G. molesta and help to develop multispecies tortricid lures for use in individual traps.EEA Alto ValleFil: Mujica, María Valentina. Instituto Nacional de Investigación Agropecuaria (INIA). Protección Vegetal; UruguayFil: Basoalto, Esteban. Universidad Austral de Chile (UACh). Facultad de Ciencias Agrarias. Instituto de Producción y Sanidad Vegetal; ChileFil: Preti, Michele. Free University of Bozen-Bolzano (UNIBZ).· Faculty of Science and Technology; ItaliaFil: Cichón, Liliana Isabel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Alto Valle; ArgentinaFil: Fuentes-Contreras, Eduardo. Universidad de Talca. Facultad de Ciencias Agrarias; ChileFil: Barros-Parada, Wilson. Pontificia Universidad Católica de Valparaíso (PUCV). Escuela de Agronomía; ChileFil: Krawczyk, Greg. Pennsylvania State University. Penn State Department of Entomology; Estados UnidosFil: Nunes, Marcelo Z. Pennsylvania State University. Penn State Department of Entomology. Fruit Research and Extension Center; Estados UnidosFil: Walgenbach, Jim F. North Carolina State University. Mountain Horticultural Crops Research & Extension Center; Estados UnidosFil: Hansen, Randy. Hansen Associates; Estados UnidosKnight, Alan L. United States Department of Agriculture (USDA). Agricultural Research Service; Estados Unido

Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways

A modified protocol for the detection of three different mRNAs with a new-generation in situ hybridization chain reaction on frozen sections

A new multiple fluorescence in situ hybridization method based on hybridization chain reaction was recently reported, enabling simultaneous mapping of multiple target mRNAs within intact zebrafish and mouse embryos. With this approach, DNA probes complementary to target mRNAs trigger chain reactions in which metastable fluorophore-labeled DNA hairpins self-assemble into fluorescent amplification polymers. The formation of the specific polymers enhances greatly the sensitivity of multiple fluorescence in situ hybridization. In this study we describe the optimal parameters (hybridization chain reaction time and temperature, hairpin and salt concentration) for multiple fluorescence in situ hybridization via amplification of hybridization chain reaction for frozen tissue sections. The combined use of fluorescence in situ hybridization and immunofluorescence, together with other control experiments (sense probe, neutralization and competition, RNase treatment, and anti-sense probe without initiator) confirmed the high specificity of the fluorescence in situ hybridization used in this study. Two sets of three different mRNAs for oxytocin, vasopressin and somatostatin or oxytocin, vasopressin and thyrotropin releasing hormone were successfully visualized via this new method. We believe that this modified protocol for multiple fluorescence in situ hybridization via hybridization chain reaction would allow researchers to visualize multiple target nucleic acids in the future

A Case-Control Study to Identify Community Venues Associated with Genetically-clustered, Multidrug-resistant Tuberculosis Disease in Lima, Peru

Background: The majority of tuberculosis transmission occurs in community settings. Our primary aim in this study was to assess the association between exposure to community venues and multidrug-resistant (MDR) tuberculosis. Our secondary aim was to describe the social networks of MDR tuberculosis cases and controls. / Methods: We recruited laboratory-confirmed MDR tuberculosis cases and community controls that were matched on age and sex. Whole-genome sequencing was used to identify genetically clustered cases. Venue tracing interviews (nonblinded) were conducted to enumerate community venues frequented by participants. Logistic regression was used to assess the association between MDR tuberculosis and person-time spent in community venues. A location-based social network was constructed, with respondents connected if they reported frequenting the same venue, and an exponential random graph model (ERGM) was fitted to model the network. / Results: We enrolled 59 cases and 65 controls. Participants reported 729 unique venues. The mean number of venues reported was similar in both groups (P = .92). Person-time in healthcare venues (adjusted odds ratio [aOR] = 1.67, P = .01), schools (aOR = 1.53, P < .01), and transportation venues (aOR = 1.25, P = .03) was associated with MDR tuberculosis. Healthcare venues, markets, cinemas, and transportation venues were commonly shared among clustered cases. The ERGM indicated significant community segregation between cases and controls. Case networks were more densely connected. / Conclusions: Exposure to healthcare venues, schools, and transportation venues was associated with MDR tuberculosis. Intervention across the segregated network of case venues may be necessary to effectively stem transmission

Time resolved particle dynamics in granular convection

We present an experimental study of the movement of individual particles in a layer of vertically shaken granular material. High-speed imaging allows us to investigate the motion of beads within one vibration period. This motion consists mainly of vertical jumps, and a global ordered drift. The analysis of the system movement as a whole reveals that the observed bifurcation in the flight time is not adequately described by the Inelastic Bouncing Ball Model. Near the bifurcation point, friction plays and important role, and the branches of the bifurcation do not diverge as the control parameter is increased. We quantify the friction of the beads against the walls, showing that this interaction is the underlying mechanism responsible for the dynamics of the flow observed near the lateral wall

Implementation of the INTERGROWTH-21st Project in Kenya

The African site in the INTERGROWTH-21(st) Project was Parklands, a wealthy suburb of Nairobi, Kenya, with a largely middle-to-high socio-economic status population. There are three hospitals with obstetric units in Parklands, with approximately 4300 births per year. The Newborn Cross-Sectional Study (NCSS) sample was drawn from all three hospitals, covering 100% of births in this target population. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from antenatal clinics serving these hospitals, using the eligibility criteria in the INTERGROWTH-21(st) protocol. Special activities to raise awareness of the study included securing media coverage and distributing leaflets in antenatal clinic waiting rooms. FGLS required women to be recruited in the first trimester; therefore, a major challenge at this study site was the high background frequency of first antenatal consultations in the second trimester. The problem was overcome by the study awareness campaign, as a result of which more women started attending antenatal care earlier in pregnancy

Waves on Reissner's membrane: a mechanism for the propagation of otoacoustic emissions from the cochlea

Sound is detected and converted into electrical signals within the ear. The cochlea not only acts as a passive detector of sound, however, but can also produce tones itself. These otoacoustic emissions are a striking manifestation of the cochlea's mechanical active process. A controversy remains of how these mechanical signals propagate back to the middle ear, from which they are emitted as sound. Here we combine theoretical and experimental studies to show that mechanical signals can be transmitted by waves on Reissner's membrane, an elastic structure within the cochea. We develop a theory for wave propagation on Reissner's membrane and its role in otoacoustic emissions. Employing a scanning laser interferometer, we measure traveling waves on Reissner's membrane in the gerbil, guinea pig, and chinchilla. The results accord with the theory and thus support a role for Reissner's membrane in otoacoustic emissions.Comment: 30 pages, 6 figures, and Supplemental informatio