Spatio-temporal remodelling of the composition and architecture of the human ovarian cortical extracellular matrix during in vitro culture

Funding: MRC grant MR/R003246/1 and Wellcome Trust Collaborative Award in Science: 215625/Z/19/Z.Study question How does in vitro culture alter the human ovarian cortical extracellular matrix (ECM) network structure? Summary answer The ECM composition and architecture vary in the different layers of the ovarian cortex and are remodelled during in vitro culture. What is known already The ovarian ECM is the scaffold within which follicles and stromal cells are organized. Its composition and structural properties constantly evolve to accommodate follicle development and expansion. Tissue preparation for culture of primordial follicles within the native ECM involves mechanical loosening; this induces undefined modifications in the ECM network and alters cell–cell contact, leading to spontaneous follicle activation. Study design, size, duration Fresh ovarian cortical biopsies were obtained from six women aged 28–38 years (mean ± SD: 32.7 ± 4.1 years) at elective caesarean section. Biopsies were cut into fragments of ∼4 × 1 × 1 mm and cultured for 0, 2, 4, or 6 days (D). Participants/materials, settings, methods Primordial follicle activation, stromal cell density, and ECM-related protein (collagen, elastin, fibronectin, laminin) positive area in the entire cortex were quantified at each time point using histological and immunohistological analysis. Collagen and elastin content, collagen fibre characteristics, and follicle distribution within the tissue were further quantified within each layer of the human ovarian cortex, namely the outer cortex, the mid-cortex, and the cortex–medulla junction regions. Main results and the role of chance Primordial follicle activation occurred concomitantly with a loosening of the ovarian cortex during culture, characterized by an early decrease in stromal cell density from 3.6 ± 0.2 × 106 at day 0 (D0) to 2.8 ± 0.1 × 106 cells/mm3 at D2 (P = 0.033) and a dynamic remodelling of the ECM. Notably, collagen content gradually fell from 55.5 ± 1.7% positive area at D0 to 42.3 ± 1.1% at D6 (P = 0.001), while elastin increased from 1.1 ± 0.2% at D0 to 1.9 ± 0.1% at D6 (P = 0.001). Fibronectin and laminin content remained stable. Moreover, collagen and elastin distribution were uneven throughout the cortex and during culture. Analysis at the sub-region level showed that collagen deposition was maximal in the outer cortex and the lowest in the mid-cortex (69.4 ± 1.2% versus 53.8 ± 0.8% positive area, respectively, P < 0.0001), and cortical collagen staining overall decreased from D0 to D2 (65.2 ± 2.4% versus 60.6 ± 1.8%, P = 0.033) then stabilized. Elastin showed the converse distribution, being most concentrated at the cortex–medulla junction (3.7 ± 0.6% versus 0.9 ± 0.2% in the outer cortex, P < 0.0001), and cortical elastin peaked at D6 compared to D0 (3.1 ± 0.5% versus 1.3 ± 0.2%, P < 0.0001). This was corroborated by a specific signature of the collagen fibre type across the cortex, indicating a distinct phenotype of the ovarian cortical ECM depending on region and culture period that might be responsible for the spatio-temporal and developmental pattern of follicular distribution observed within the cortex. Large scale data N/A. Limitations, reasons for caution Ovarian cortical biopsies were obtained from women undergoing caesarean sections. As such, the data obtained may not accurately reflect the ECM distribution and structure of non-pregnant women. Wider implications of the findings Clarifying the composition and architecture signature of the human ovarian cortical ECM provides a foundation for further exploration of ovarian microenvironments. It is also critical for understanding the ECM–follicle interactions regulating follicle quiescence and awakening, leading to improvements in both in vitro activation and in vitro growth techniques.Publisher PDFPeer reviewe

Transcribing Reality: how the nature of audio and visual media have affected culture, perception, and the role of the artist.

The research presented in this thesis was motivated by my own need as a composer to position my work within the broadening of artistic practice that has become a significant aspect of the contemporary music scene. Roughly speaking, this research consists of two interconnected topics: the nature of the complex relationship between reality and the means we have to record it, and a rethinking of the audio visual correlations that might arise as a result of such an investigation into the workings of media. Through the study of these two topics, further important issues will be brought to light such as the distinction between discrete and continuous recording methods, ideas of medial loss, intermedia, and the role that we ourselves play in the development and consumption of media, and as makers and spectators of artworks that use media. I will investigate these questions through my own artistic work. This work, as befits the research topic, employs a variety of formats including some, such as film and audio-visual installation which I have never used before. As a counterpoint to my portfolio I have chosen to examine a carefully selected set of pieces by other artists, also in a variety of media, that taken as a whole help to outline the artistic and theoretical territory to be studied. The investigations of my own work as well as of these case studies are knitted together with theory drawn from a wide range of sources including psychology, science, art, media and music theory, in addition to ideas gleaned from fiction, in order to form the basis of the written part of my thesis. The text is divided into an introductory chapter, three main chapters and a concluding chapter, and has a quasi-historical trajectory starting with the long-exposure that characterized early photography, moving through the single short sample, to the stringing of these samples together into film and digital audio. The fourth chapter concerns sound film, synchronisation and the FT domain, and explores what happens when we put sound and image together, or try to imagine one through the lens of the other. The concluding chapter deals with recent developments in media technology such as high film frame rates and the domination of the digital world, and examines the problematics associated with these developments

Conceptualizing the adventure-sports coach

As a comparatively recent development, the adventure-sports coach struggles for a clear and distinct identity. The generic term ‘instructor’ no longer characterizes the role and function of this subgroup of outdoor professionals. Indeed, although the fields of adventure/outdoor education and leadership are comparatively well researched, the arrival of this ‘new kid on the block’ appears to challenge both the adventure-sports old guard and traditional views of sports coaching. In an attempt to offer clarity and stimulate debate, this paper attempts to conceptualize the adventure-sports coach in the context of the existing roles in the field and current motivations for activity in the outdoors. We identify issues that are specific to the adventure-sports coach while also recognizing those skills and competencies shared with other professionals, both in the adventure sports profession and traditional sports coaching fields. Based on this review, we offer a conceptual model which may be used to focus debate, stimulate research and, at a possible later stage, to underpin accreditation, training and professional development

Continuous quality improvement and metabolic screening during pregnancy at primary health centres attended by Aboriginal and Torres Strait Islander women

Objective: To investigate associations between the provision of routine metabolic screening and follow-up in pregnancy and participation by primary health care centres in a large-scale continuous quality improvement (CQI) initiative.Design: Longitudinal analysis of 2592 audited maternal health records.Setting and participants: Seventy-six community-controlled or government-operated primary health care centres serving predominantly Aboriginal and Torres Strait Islander communities, in urban, regional or remote locations in five Australian states and territories.Intervention: Up to four CQI cycles supported by the Audit and Best Practice for Chronic Disease Research Partnership.Main outcomes measures:Screening and follow-up for body mass index (BMI), blood pressure and diabetes in pregnancy.Results: Overall, 87.9% of women attending the participating health centres were Aboriginal or Torres Strait Islander. Women attending a health centre after it had conducted one or more CQI cycles were more likely to receive BMI, blood pressure and diabetes screening. For example, the proportion of women receiving diabetes screening at baseline (before the first CQI cycle) was 56.1%; after cycle 1 it was 63.7% (odds ratio [OR], 1.3; 95% CI, 1.0&ndash;1.6), after cycle 2, 61.6% (OR, 1.2; 95% CI, 0.9&ndash;1.7), after cycle 3, 63.7% (OR, 1.7; 95% CI, 1.1&ndash;2.6), and after cycle 4, 75.5% (OR, 3.4; 95% CI, 1.9&ndash;5.9). Diabetes screening was associated with higher self-ratings of overall organisational systems (P = 0.03), self-management support (P = 0.04) and organisational influence and integration (P = 0.01).Conclusion: These findings support the value of CQI approaches that focus on systems-level issues in primary care to improve the provision of recommended pregnancy care at primary health care centres in predominantly Aboriginal and Torres Strait Islander communities

Understanding uptake of continuous quality improvement in Indigenous primary health care: lessons from a multi-site case study of the Audit and Best Practice for Chronic Disease project

<p>Abstract</p> <p>Background</p> <p>Experimentation with continuous quality improvement (CQI) processes is well underway in Indigenous Australian primary health care. To date, little research into how health organizations take up, support, and embed these complex innovations is available on which services can draw to inform implementation. In this paper, we examine the practices and processes in the policy and organisational contexts, and aim to explore the ways in which they interact to support and/or hinder services' participation in a large scale Indigenous primary health care CQI program.</p> <p>Methods</p> <p>We took a theory-driven approach, drawing on literature on the theory and effectiveness of CQI systems and the Greenhalgh diffusion of innovation framework. Data included routinely collected regional and service profile data; uptake of tools and progress through the first CQI cycle, and data collected quarterly from hub coordinators on their perceptions of barriers and enablers. A total of 48 interviews were also conducted with key people involved in the development, dissemination, and implementation of the Audit and Best Practice for Chronic Disease (ABCD) project. We compiled the various data, conducted thematic analyses, and developed an in-depth narrative account of the processes of uptake and diffusion into services.</p> <p>Results</p> <p>Uptake of CQI was a complex and messy process that happened in fits and starts, was often characterised by conflicts and tensions, and was iterative, reactive, and transformational. Despite initial enthusiasm, the mixed successes during the first cycle were associated with the interaction of features of the environment, the service, the quality improvement process, and the stakeholders, which operated to produce a set of circumstances that either inhibited or enabled the process of change. Organisations had different levels of capacity to mobilize resources that could shift the balance toward supporting implementation. Different forms of leadership and organisational linkages were critical to success. The Greenhalgh framework provided a useful starting point for investigation, but we believe it is more a descriptive than explanatory model. As such, it has limitations in the extent to which it could assist us in understanding the interactions of the practices and processes that we observed at different levels of the system.</p> <p>Summary</p> <p>Taking up CQI involved engaging multiple stakeholders in new relationships that could support services to construct shared meaning and purpose, operationalise key concepts and tools, and develop and embed new practices into services systems and routines. Promoting quality improvement requires a system approach and organization-wide commitment. At the organization level, a formal high-level mandate, leadership at all levels, and resources to support implementation are needed. At the broader system level, governance arrangements that can fulfil a number of policy objectives related to articulating the linkages between CQI and other aspects of the regulatory, financing, and performance frameworks within the health system would help define a role and vision for quality improvement.</p

Exploring cross-sectional associations between common childhood illness, housing and social conditions in remote Australian Aboriginal communities

Background:\ud There is limited epidemiological research that provides insight into the complex web of causative and moderating factors that links housing conditions to a variety of poor health outcomes. This study explores the relationship between housing conditions (with a primary focus on the functional state of infrastructure) and common childhood illness in remote Australian Aboriginal communities for the purpose of informing development of housing interventions to improve child health.\ud \ud Methods:\ud Hierarchical multi-level analysis of association between carer report of common childhood illnesses and functional and hygienic state of housing infrastructure, socio-economic, psychosocial and health related behaviours using baseline survey data from a housing intervention study.\ud \ud Results:\ud Multivariate analysis showed a strong independent association between report of respiratory infection and overall functional condition of the house (Odds Ratio (OR) 3.00; 95%CI 1.36-6.63), but no significant association between report of other illnesses and the overall functional condition or the functional condition of infrastructure required for specific healthy living practices. Associations between report of child illness and secondary explanatory variables which showed an OR of 2 or more included: for skin infection - evidence of poor temperature control in the house (OR 3.25; 95%CI 1.06-9.94), evidence of pests and vermin in the house (OR 2.88; 95%CI 1.25-6.60); for respiratory infection - breastfeeding in infancy (OR 0.27; 95%CI 0.14-0.49); for diarrhoea/vomiting - hygienic state of food preparation and storage areas (OR 2.10; 95%CI 1.10-4.00); for ear infection - child care attendance (OR 2.25; 95%CI 1.26-3.99).\ud \ud Conclusion:\ud These findings add to other evidence that building programs need to be supported by a range of other social and behavioural interventions for potential health gains to be more fully realised

The European Union, borders and conflict transformation: the case of Cyprus

Much of the existing literature on the European Union (EU), conflict transformation and border dynamics has been premised on the assumption that the nature of the border determines EU intervention and the consequences that flow from this in terms of EU impact. The article aims to transcend this literature through assessing how domestic interpretations influence EU border transformation in conflict situations, taking Cyprus as a case study. Moreover, the objective is to fuse the literature on EU bordering impact and perceptions of the EU’s normative projection in conflict resolution. Pursuing this line of inquiry is an attempt to depart from the notion of borders being constructed solely by unidirectional EU logics of engagement or bordering practices to a conceptualization of the border as co-constituted space, where the interpretations of the EU’s normative projections by conflict parties, and the strategies that they pursue, can determine the relative openness of the EU border