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The process of parturition resulting in the delivery of a newborn is a fundamental event ensuring survival of the species. In humans, the main clinical problems of parturition include activation of the process too early or too late resulting in the delivery of pre-term and post-term infants, both with their own implications for future health for the mother and baby. Additionally, where parturition systems are not activated correctly, dysfunctional labour with the resulting need for caesarean delivery (CS), in addition to atonic post-partum haemorrhage can also ensue. Overall, in the UK up to 40% of pregnancies are affected by one of these problems. However, the exact processes involved in the initiation and maintenance of parturition in the human are not fully understood. With such an important event, influences are most likely to be multi-factorial, with hormonal, mechanical, inflammatory, biochemical and maternal environmental factors playing a part. The aims of this thesis were to investigate influences on parturition in human pregnancy. Firstly, the myometrial transcriptional effects of long term exposure to the uterotonic oxytocin (OT) were examined. Further investigation of the myometrial and maternal peripheral response to uterine contractions in-vitro and in-vivo was also made with particular reference to the role of inflammation and myocyte damage. Additionally, the influence of maternal factors, particularly obesity, on the myometrial in-vitro contractile function and response to OT was studied. Initially, 150 gene arrays were produced using the Illumina platform. The samples were derived from myometrium taken at pre-labour CS which subsequently underwent functional contractility experiments in an organ bath. Five drug environments were studied, namely OT, acetic acid (OT vehicle), ML7(a tocolytic acting via inhibition of myosin light chain kinase), ML7 & OT and finally DMSO (ML7 vehicle). Additionally, five time-points of 0, 1, 2, 4, and 6 hours after drug addition were used, resulting in 5 samples for each drug and time combination. The results indicated that despite a clear enhancement of myometrial contractile activity by OT, this functional response does not appear to be mediated by cellular transcription. However, there was a clear contraction and time dependent transcriptional wave, with overrepresentation of genes associated with inflammation and cellular damage/apoptosis, and down-regulation of pathways concerning cellular metabolism. These findings were confirmed by QPCR on further myometrial samples undergoing additional in-vitro functional studies. In addition to the temporal and contractile association with the inflammatory response, our data suggest inflammation occurs in response to myocyte cellular damage regardless of mode of damage e.g. contractile or chemically induced. This was demonstrated by inflammatory upregulation in myometrium exposed to the tocolytic agents nifedipine and ritodrine, which is not seen in response to ML7. Additionally, the myometrial inflammatory response was enhanced by the infective agent LPS. However, contrary to other proposals, the enhanced inflammatory response of the myometrium did not alter or promote the in-vitro contractile ability of the myometrium or its response to OT. This myometrial transcriptional data therefore suggests that the inflammatory response of labour is associated with contraction, chemical or infection induced myometrial cellular damage, but would not be considered necessary for a contractile response. Our in-vivo study of peripheral changes in the maternal circulation again supported our in-vitro myometrial data. Data showed that the effect of pregnancy at term was limited to increased white cell count driven by a neutrophilia, with no suggestion of leukocyte priming prior to labour. Additionally, term pregnancy is associated with an increase in CRP, an increase in GCSF (corresponding with the neutrophilia) in addition to suppression of the chemokines CCL11 and CCL22. Subsequently, we found that repeated blood samples taken at 2 hourly intervals during term labour induced dramatic changes in inflammatory cells and inflammatory mediators in the maternal circulation. Importantly, these changes occur in a co-ordinated time and contraction dependent manner, with the degree of inflammation associated with the length of time in labour and the degree of myocyte damage as measured by circulating CK and Mb. Our study of the influence of maternal factors on myometrial contractile ability and response to OT examined in-vitro myometrial contractility of 609 myometrial strips from 85 women. We demonstrated that maternal obesity does not impair spontaneous or OT induced myometrial contractions in-vitro. Furthermore, maternal age, ethnicity, parity, previous caesarean delivery,gestation at delivery and birthweight do not influence in-vitro myometrial spontaneous or OT induced contractile activity. This therefore suggests that the observed implication of these maternal and infant factors on parturition in-vivo (high rates of induction of labour, high rates of intrapartum caesarean delivery and post partum haemorrhage) cannot be explained by an effect on myometrial contraction per se. This therefore merits further investigation as to alternative mechanisms to ultimately promote and effective, uncomplicated and safe labour and vaginal delivery for at risk mothers. In summary, this thesis provides evidence that the myometrial contractions of human labour, whether spontaneous or OT induced are capable of inducing a temporal wave of transcriptional changes associated with the processes of inflammation, cellular damage/apoptosis with inhibition of cellular metabolic processes. In addition, maternal peripheral circulating factors mirror the myometrial transcriptional changes. These changes are highly comparable with those seen in response to exercising skeletal muscle, and in this model have been shown to play an important role in muscle repair and remodelling after exercise. Therefore, we would suggest that the inflammatory reaction typically associated with human labour occurs as a non-specific response to contraction induced cellular damage and may play a role in postpartum repair and remodelling of the uterus.

This thesis aims to improve historical knowledge of Australian refugee policy between 1976 and 1983, a unique and transitional moment in the nation’s history and in international refugee movements. The discussion will be based on original evidence drawn from archival records and oral history interviews, and informed by a broad literature which recognises that refugee policy is a product of varied political imperatives and historical context. First, Chapter Three reveals that because the Fraser government could not deport the Indochinese boatpeople who sailed to Australia, it sought to approve their refugee status in order to legitimate its announcements that only ‘genuine’ refugees were being admitted. In doing so, the Fraser government was required to defend the processing of boat arrivals to the public and within the bureaucracy. Chapter Four finds that historical and political considerations informed the Fraser government’s choice not to reject or detain boat arrivals but to instead introduce legislation against people smuggling. The chapter presents new evidence to disprove claims expressed in recent academic and media commentary that the government’s Immigration (Unauthorised Arrivals) Act 1980 (Cth) marked a particularly harsh stance and that passengers on the VT838 were deported without due process, and draws from ideas within the literature concerning the need for states to promote the integrity of the refugee concept. Chapter Five contributes to international literature on refugee status determination procedure by studying the Australian government’s assessment of non-Indochinese. Through a dataset created from UNHCR archives it is found that the quality of briefing material and political considerations could influence deliberations on individual cases. Chapter Six contributes to literature on in-country processing, revealing how Australia’s programme in Chile and El Salvador was a means of diversifying the refugee intake but caused tensions between the Department of Immigration and the Department of Foreign Affairs.

The hair follicle has the unique capacity to pass through periods of growth, regression and rest before regenerating itself to restart the cycle. This dynamic cycling capacity enables animals to change their coats, and for hair length to be controlled at different body sites. While progress has been made on some of the outstanding questions in hair follicle biology, many of the cellular and molecular mechanisms involved in driving hair follicle cycling remain undiscovered. The first section of work in this thesis reports on the dermal papilla, an essential component of the hair follicle with a key role in follicle regeneration. Using hanging drop cultures spheres of human dermal papilla cells were created, and the expression of cytoskeletal and extracellular matrix components characteristic of intact papillae were analysed using immunohistochemistry and real time PCR. I found evidence that over time the gene and protein expression profiles of the papilla cell spheres became more representative of intact dermal papillae, although differences were seen between papilla cells strains derived from different individuals. I then demonstrated the inductive capability of human dermal papilla cells using this spherical model in an amputated follicle assay. This data provides some of the first evidence that cultured human dermal papilla cells can retain inductive capacity without having to be combined with other cell types. This induction phenomenon may also have relevance to anagen initiation and cycling. The second section of this thesis was concentrated on the process of club fibre shedding, now widely recognised as a phase of the follicle cycle known as exogen. The vibrissa follicle, with its predictable timing of club fibre loss, was first developed as a new model for exogen, and the structural and adhesive changes associated with the progression towards club fibre release were analysed using SEM and ТЕМ. Combined with plucking experiments these showed club loss to be gradual process. The expression of proteins involved in cell adhesion, differentiation, communication and digestion, all potential mediators of fibre loss were examined around "young “and "old" club fibres using immunohistochemistry. To further assess the mechanism of exogen, and to search for signalling molecules microarray technology was utilised, enabling the identification of 75 genes that were associated with the process. Group analysis highlighted a particular role for proteases and their inhibitors in the retention and final release of the club fibre. Moreover, immunofluorescent analysis of the results from the microarray identified a process of differentiation, specific to the cell layer surrounding the club fibre prior to club fibre release. This data provides evidence that the process of exogen is progressive, associated with maturation of the cells surrounding the club fibre, and terminating with the release of the club fibre. The processes involved in club fibre release are becoming more widely recognised as an important aspect of the hair cycle and this thesis is one of the first comprehensive pieces of work that analyses club retention and release as an active phase.

Inadequate preparation, combined with challenging work conditions, contribute to the shortage of skilled special educators in the United States (Levenson, 2011). Because teacher quality is linked to student achievement (Darling-Hammond, 2001), the discrepancy in access to qualified teachers has remained a serious issue, particularly for students with emotional and behavioral disabilities (EBD), whose intensive needs present great obstacles to learning. Although the research identifies strong content knowledge and social emotional competence as critical skills for educators (Bridgeland, Bruce, & Hariharan, 2012; Shulman, 1986), current standards for licensure (as they apply to EBD teachers) largely overlook these attributes (Massachusetts Department of Elementary and Secondary Education, 2011a), leaving teachers poorly equipped to address the needs of the students in their classrooms and making them more vulnerable to burnout (Adams, 2013). This mixed methods study explored the issues of teacher preparation and self-efficacy as they relate to secondary special educators who serve students with EBD in Massachusetts. This research employed a sequential explanatory design, utilizing 118 surveys and six telephone interviews to: (a) identify how secondary special educators who teach students with EBD are prepared; (b) explore their self-efficacy regarding their ability to teach secondary level content and to respond to the social and emotional needs of their students; and (c) understand how they explain the factors that influence their self-efficacy in the classroom. Results revealed the limited effect of credentials (such as licensure and/or a degree) on EBD teacher self-efficacy as well as the impact of school culture. In particular, several implications emerged related to the preparation and support of this population of teachers: (a) content area credentials had no bearing on teacher self-efficacy and (b) special education credentials negatively impacted self-efficacy for teaching content, while (c) training in social and emotional learning positively impacted self-efficacy related to social emotional responsiveness and special education pedagogy. Additionally, results suggested that (d) private school employment increased self-efficacy for teaching content and (e) administrative support strengthened self-efficacy for applying special education strategies. Findings may be useful to school districts, educator preparation programs, and policymakers as they consider how to support educators in this field. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]