A quantitative exploration of the sociocultural context of teenage pregnancy in Sri Lanka

Background: In common with other countries, teenage pregnancy is attracting policy attention in Sri Lanka because of the risks it poses to maternal and infant health and social and economic well-being. This study aimed to increase understanding of the context of teenage pregnancy, by (1) describing the socio-economic and demographic characteristics of pregnant teenagers and their partners; (2) exploring whether teenage pregnancies are planned and how they are received; and (3) exploring factors associated with unplanned teenage pregnancy. Methods: A population health-register based sample survey was conducted in Badulla District, Sri Lanka. Interviewer-administered questionnaires were administered to two samples: 450 pregnant women aged less than 20years; and 150 male partners of pregnant women aged less than 20years. Bivariate statistics described the characteristics and context of teenage pregnancy. Multivariate logistic regression explored correlates of unplanned pregnancy. Results: Over 60% of pregnant teenagers and male partners indicated that the current pregnancy was planned; while 79% of pregnant teenagers and 85% of male partners welcomed the pregnancy. Most pregnant teenagers were living within stable and supportive family environments, with 94% reporting that they felt 'very well supported'. Nevertheless, a sub-group of pregnant teenagers appeared to be vulnerable, reporting unplanned and unhappy pregnancy; factors that were also associated with first intercourse being reported as not wanted. Levels of reproductive and contraceptive knowledge were poor among both pregnant teenagers and male partners. Just 46% of teenagers and 64% of male partners knew that pregnancy was possible at first intercourse. Mothers appear to be an important source of information and support for young women, with peers being reported far less often. Conclusions: Intervention to reduce teenage pregnancy must recognise the normative nature of early childbearing for the majority of girls who currently conceive and their families. Avoiding such pregnancies will require a fundamental shift in life chances such that delaying pregnancy offers significant socioeconomic advantages. Meanwhile, improved provision of contraceptive information and services is needed to support the delay of second pregnancies for young mothers. In addition, strategies to identify and protect those girls who are vulnerable to unwanted sexual activity are needed.</p

Cortical Tension Allocates the First Inner Cells of the Mammalian Embryo

Every cell in our body originates from the pluripotent inner mass of the embryo, yet it is unknown how biomechanical forces allocate inner cells in vivo. Here we discover subcellular heterogeneities in tensile forces, generated by actomyosin cortical networks, which drive apical constriction to position the first inner cells of living mouse embryos. Myosin II accumulates specifically around constricting cells, and its disruption dysregulates constriction and cell fate. Laser ablations of actomyosin networks reveal that constricting cells have higher cortical tension, generate tension anisotropies and morphological changes in adjacent regions of neighboring cells, and require their neighbors to coordinate their own changes in shape. Thus, tensile forces determine the first spatial segregation of cells during mammalian development. We propose that, unlike more cohesive tissues, the early embryo dissipates tensile forces required by constricting cells via their neighbors, thereby allowing confined cell repositioning without jeopardizing global architecture.Fil: Samarage, Chaminda R.. Monash University; AustraliaFil: White, Melanie D.. Monash University; AustraliaFil: Alvarez, Yanina Daniela. Monash University; Australia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fierro González, Juan Carlos. Monash University; AustraliaFil: Henon, Yann. Monash University; AustraliaFil: Jesudason, Edwin C.. National Health Service Scotland; Reino UnidoFil: Bissiere, Stephanie. Monash University; Australia. Institute of Molecular and Cell Biology; SingapurFil: Fouras, Andreas. Monash University; AustraliaFil: Plachta, Nicolas. Monash University; Australia. Institute of Molecular and Cell Biology; Singapu

Quantification of muco-obstructive lung disease variability in mice via laboratory X-ray velocimetry

To effectively diagnose, monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung. This capability would enable any decline or improvement in health to be located and measured, allowing improved treatment options to be designed. Current lung function assessment methods have many limitations, including the inability to accurately localise the origin of global changes within the lung. However, X-ray velocimetry (XV) has recently been demonstrated to be a sophisticated and non-invasive lung function measurement tool that is able to display the full dynamics of airflow throughout the lung over the natural breathing cycle. In this study we present two developments in XV analysis. Firstly, we show the ability of laboratory-based XV to detect the patchy nature of cystic fibrosis (CF)-like disease in β-ENaC mice. Secondly, we present a technique for numerical quantification of CF-like disease in mice that can delineate between two major modes of disease symptoms. We propose this analytical model as a simple, easy-to-interpret approach, and one capable of being readily applied to large quantities of data generated in XV imaging. Together these advances show the power of XV for assessing local airflow changes. We propose that XV should be considered as a novel lung function measurement tool for lung therapeutics development in small animal models, for CF and for other muco-obstructive diseases.Freda Werdiger, Martin Donnelley, Stephen Dubsky, Rhiannon P. Murrie, Richard P. Carnibella, Chaminda R. Samarage ... et al

Quantification of heterogeneity in lung disease with image-based pulmonary function testing

Published: 27 July 2016Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children, and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls; identified locations of airway obstruction, and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool.Charlene S. Stahr, Chaminda R. Samarage, Martin Donnelley, Nigel Farrow, Kaye S. Morgan, Graeme Zosky, Richard C. Boucher, Karen K. W. Siu, Marcus A. Mall, David W. Parsons, Stephen Dubsky and Andreas Foura

The DESiGN trial (DEtection of Small for Gestational age Neonate), evaluating the effect of the Growth Assessment Protocol (GAP): study protocol for a randomised controlled trial.

BACKGROUND: Stillbirth rates in the United Kingdom (UK) are amongst the highest of all developed nations. The association between small-for-gestational-age (SGA) foetuses and stillbirth is well established, and observational studies suggest that improved antenatal detection of SGA babies may halve the stillbirth rate. The Growth Assessment Protocol (GAP) describes a complex intervention that includes risk assessment for SGA and screening using customised fundal-height growth charts. Increased detection of SGA from the use of GAP has been implicated in the reduction of stillbirth rates by 22%, in observational studies of UK regions where GAP uptake was high. This study will be the first randomised controlled trial examining the clinical efficacy, health economics and implementation of the GAP programme in the antenatal detection of SGA. METHODS/DESIGN: In this randomised controlled trial, clusters comprising a maternity unit (or National Health Service Trust) were randomised to either implementation of the GAP programme, or standard care. The primary outcome is the rate of antenatal ultrasound detection of SGA in infants found to be SGA at birth by both population and customised standards, as this is recognised as being the group with highest risk for perinatal morbidity and mortality. Secondary outcomes include antenatal detection of SGA by population centiles, antenatal detection of SGA by customised centiles, short-term maternal and neonatal outcomes, resource use and economic consequences, and a process evaluation of GAP implementation. Qualitative interviews will be performed to assess facilitators and barriers to implementation of GAP. DISCUSSION: This study will be the first to provide data and outcomes from a randomised controlled trial investigating the potential difference between the GAP programme compared to standard care for antenatal ultrasound detection of SGA infants. Accurate information on the performance and service provision requirements of the GAP protocol has the potential to inform national policy decisions on methods to reduce the rate of stillbirth. TRIAL REGISTRATION: Primary registry and trial identifying number: ISRCTN 67698474 . Registered on 2 November 2016

Effect of the Growth Assessment Protocol on the DEtection of Small for GestatioNal age fetus: process evaluation from the DESiGN cluster randomised trial

BACKGROUND: Reducing the rate of stillbirth is an international priority. At least half of babies stillborn in high-income countries are small for gestational-age (SGA). The Growth Assessment Protocol (GAP), a complex antenatal intervention that aims to increase the rate of antenatal detection of SGA, was evaluated in the DESiGN type 2 hybrid effectiveness-implementation cluster randomised trial (n = 13 clusters). In this paper, we present the trial process evaluation. METHODS: A mixed-methods process evaluation was conducted. Clinical leads and frontline healthcare professionals were interviewed to inform understanding of context (implementing and standard care sites) and GAP implementation (implementing sites). Thematic analysis of interview text used the context and implementation of complex interventions framework to understand acceptability, feasibility, and the impact of context. A review of implementing cluster clinical guidelines, training and maternity records was conducted to assess fidelity, dose and reach. RESULTS: Interviews were conducted with 28 clinical leads and 27 frontline healthcare professionals across 11 sites. Staff at implementing sites generally found GAP to be acceptable but raised issues of feasibility, caused by conflicting demands on resource, and variable beliefs among clinical leaders regarding the intervention value. GAP was implemented with variable fidelity (concordance of local guidelines to GAP was high at two sites, moderate at two and low at one site), all sites achieved the target to train > 75% staff using face-to-face methods, but only one site trained > 75% staff using e-learning methods; a median of 84% (range 78–87%) of women were correctly risk stratified at the five implementing sites. Most sites achieved high scores for reach (median 94%, range 62–98% of women had a customised growth chart), but generally, low scores for dose (median 31%, range 8–53% of low-risk women and median 5%, range 0–17% of high-risk women) were monitored for SGA as recommended. CONCLUSIONS: Implementation of GAP was generally acceptable to staff but with issues of feasibility that are likely to have contributed to variation in implementation strength. Leadership and resourcing are fundamental to effective implementation of clinical service changes, even when such changes are well aligned to policy mandated service-change priorities. TRIAL REGISTRATION: Primary registry and trial identifying number: ISRCTN 67698474. Registered 02/11/16. https://doi.org/10.1186/ISRCTN67698474

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial

BACKGROUND: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. METHODS AND FINDINGS: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. CONCLUSIONS: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry, ISRCTN67698474

Rare-Earth-Activated Group Vi D0 Metal Oxides As Thermosensitive Phosphors

ABSTRACT RARE-EARTH-ACTIVATED GROUP VI d0 METAL OXIDES AS THERMOSENSITIVE PHOSPHORS by SAMARAGE SAMEERA PRASAD PERERA AUGUST 2019 Advisor: Dr. Federico A. Rabuffetti Major: Chemistry Degree: Doctor of Philosophy Thermosensitive phosphors are solid-state materials that demonstrate distinct dependence of luminescence emission on temperature. These materials enable optical temperature sensing in environments where conventional thermometry is not possible (e.g., gas turbines, combustion engines, surface temperature distributions). However, the design of thermosensitive phosphors that show adequate sensitivity and low thermal quenching in the intermediate temperature range (i.e., 500–1000 K) remains challenging. This challenge can be addressed by understanding how to rationally manipulate the phosphor’s chemical composition and the crystal structure to tailor their thermometric response. With the aim of bridging this knowledge gap, this dissertation presents an investigation of the temperature-dependent luminescence response of a series of chemically and structurally tunable phosphors. Solid-state synthesis, structural characterization, and temperature-dependent luminescence response of rare-earth-activated scheelite and scheelite-related phosphors are presented to this end. Thermometric response of a series of Dy3+-activated NaLa(MO4)2 and Na5La(MO4)4 single-emitter phosphors in 300–700 K temperature range was investigated. Their potential as thermosensitive phosphors were revealed. Dual-emitter phosphors featuring two rare-earth ions with different thermal quenching characteristics were developed. Upon investigating their thermometric response, the advantage of using dual-emitter phosphors over single-emitter phosphors to overcome the effect of thermal quenching on relative sensitivity was revealed. Finally, the importance of coupling rare-earth and transition metal ions to develop dual-emitter phosphors to improve the thermometric sensitivity and exploring new host for thermosensitive phosphors was highlighted

Advances in image-based quantitative measurements in biological imaging

The greatest innovations in microscopy now occur after image acquisition. Digital image processing techniques continue to improve microscopy driving scientific discovery in the 21st century. This thesis presents original knowledge in the development of advanced digital processing methods for quantification of the three distinct physical attributes of shape, motion and force. A key area in microscopy is imaging of biological samples with low contrast. This thesis presents an alternative three-dimensional tomographic microscopy method, termed Refractive Index Tomography (RIT), which uses the refractive properties of the specimen for imaging without the need for fluorescent labels. RIT uses a straightforward, low-cost optical setup with an algorithm applicable to both visible light and X-ray-based microscopy, further demonstrating the versatility of software over hardware in the modern microscope. Motion and flow are increasingly being understood to play a large role across a wide range of biological processes. Particle Image Velocimetry (PIV) is an image-based technique developed for fluid dynamics research, and has recently gained interest amongst biological researchers for studies involving the quantification of biological motion and flow. However, limitations in optical setup and access to the region of interest compromises image quality through low light, low contrast and uneven illumination. This thesis presents two processes for refining PIV by addressing these issues. The first is a hybrid averaging process that combines and optimises two averaging methods to reduce the effect of image noise on flow measures. The second is Polynomial Element Velocimetry, a completely new variant of PIV designed for quantifying flow and flow gradients in complex biological flows from images with limited resolution and contrast. Quantification and characterisation of the role of biomechanical forces in early embryonic development is of increasing interest to researchers. This thesis develops a novel technique to quantify cortical tensile forces in living mouse embryos. Four-dimensional cell segmentation and tracking were used to demonstrate that inter-cellular forces within the embryo are required for the formation of viable embryos. This critical advancement in evidence suggests mechanical forces may be used to control pluripotency of embryonic stem cells needed for tissue regeneration and treatment of disease. Advances from image processing software have enabled the capture of dramatically more functional information over what is possible with hardware alone. The studies presented in this thesis represent developments in image processing that will continue to drive digital microscopy, from visualisation of structures into an increasingly powerful tool for quantification of physical processes

postgraduate training programme

perception of the clinical learning environment in th