Computer planning of stereotactic iodine-125 seed brachytherapy for recurrent malignant gliomas

At St Thomas' Hospital, we have developed a computer program on a Titan graphics supercomputer to plan the stereotactic implantation of iodine-125 seeds for the palliative treatment of recurrent malignant gliomas. Use of the Gill-Thomas-Cosman relocatable frame allows planning and surgery to be carried out at different hospitals on different days. Stereotactic computed tomography (CT) and positron emission tomography (PET) scans are performed and the images transferred to the planning computer. The head, tumour and frame fiducials are outlined on the relevant images, and a three-dimensional model generated. Structures which could interfere with the surgery or radiotherapy, such as major vessels, shunt tubing etc., can also be outlined and included in the display. Catheter target and entry points are set using a three-dimensional cursor controlled by a set of dials attached to the computer. The program calculates and displays the radiation dose distribution within the target volume for various catheter and seed arrangements. The CT co-ordinates of the fiducial rods are used to convert catheter co-ordinates from CT space to frame space and to calculate the catheter insertion angles and depths. The surgically implanted catheters are after-loaded the next day and the seeds left in place for between 4 and 6 days, giving a nominal dose of 50 Gy to the edge of the target volume. 25 patients have been treated so far.

Doing blog research

Blogs and other online platforms for personal writing such as LiveJournal have been of interest to researchers across the social sciences and humanities for a decade now. Although growth in the uptake of blogging has stalled somewhat since the heyday of blogs in the early 2000s, blogging continues to be a major genre of Internet-based communication. Indeed, at the same time that mass participation has moved on to Facebook, Twitter, and other more recent communication phenomena, what has been left behind by the wave of mass adoption is a slightly smaller but all the more solidly established blogosphere of engaged and committed participants. Blogs are now an accepted part of institutional, group, and personal communications strategies (Bruns and Jacobs, 2006); in style and substance, they are situated between the more static information provided by conventional Websites and Webpages and the continuous newsfeeds provided through Facebook and Twitter updates. Blogs provide a vehicle for authors (and their commenters) to think through given topics in the space of a few hundred to a few thousand words – expanding, perhaps, on shorter tweets, and possibly leading to the publication of more fully formed texts elsewhere. Additionally, they are also a very flexible medium: they readily provide the functionality to include images, audio, video, and other additional materials – as well as the fundamental tool of blogging, the hyperlink itself. Indeed, the role of the link in blogs and blog posts should not be underestimated. Whatever the genre and topic that individual bloggers engage in, for the most part blogging is used to provide timely updates and commentary – and it is typical for such material to link both to relevant posts made by other bloggers, and to previous posts by the present author, both to background material which provides readers with further information about the blogger’s current topic, and to news stories and articles which the blogger found interesting or worthy of critique. Especially where bloggers are part of a larger community of authors sharing similar interests or views (and such communities are often indicated by the presence of yet another type of link – in blogrolls, often in a sidebar on the blog site, which list the blogger’s friends or favourites), then, the reciprocal writing and linking of posts often constitutes an asynchronous, distributed conversation that unfolds over the course of days, weeks, and months. Research into blogs is interesting for a variety of reasons, therefore. For one, a qualitative analysis of one or several blogs can reveal the cognitive and communicative processes through which individual bloggers define their online identity, position themselves in relation to fellow bloggers, frame particular themes, topics and stories, and engage with one another’s points of view. It may also shed light on how such processes may differ across different communities of interest, perhaps in correlation with the different societal framing and valorisation of specific areas of interest, with the socioeconomic backgrounds of individual bloggers, or with other external or internal factors. Such qualitative research now looks back on a decade-long history (for key collections, see Gurak, et al., 2004; Bruns and Jacobs, 2006; also see Walker Rettberg, 2008) and has recently shifted also to specifically investigate how blogging practices differ across different cultures (Russell and Echchaibi, 2009). Other studies have also investigated the practices and motivations of bloggers in specific countries from a sociological perspective, through large-scale surveys (e.g. Schmidt, 2009). Blogs have also been directly employed within both K-12 and higher education, across many disciplines, as tools for reflexive learning and discussion (Burgess, 2006).

Do anti-inflammatory agents promote linear ablation lesion discontinuities? : an electrophysiological examination

Background: Catheter ablation for atrial fibrillation (AF) is more efficacious than antiarrhythmic therapy. Post ablation recurrences reduce ablation effectiveness and are contributed by lesion discontinuity in the fibrotic linear ablation lesions. The anti-fibrotic role of statins in reducing AF is being assessed in current trials. By reducing the chronic pathological fibrosis that occurs in AF they may reduce AF. However if statins also have an effect on the acute therapeutic fibrosis of an ablation, this could exacerbate lesion discontinuity and AF recurrence. We tested the hypothesis that statins attenuate ablation lesion continuity in a recognised pig atrial linear ablation model. Aims: To assess whether Atorvastatin diminishes the bi-directional conduction block produced by a linear atrial ablation lesion. Methods: Sixteen pigs were randomised to statin (n=8) or placebo (n=8) with drug pre-treatment for 3 days and a further 4 weeks. At initial electrophysiological study (EPS1) 3D right atrium (RA) mapping and a vertical ablation linear lesion in the posterior RA with bidirectional conduction block were completed (Gepstein Circ 1999). Follow-up electrophysiological assessment (EPS2) at 28 days assessed bidirectional conduction block maintenance. Results: Data of 15/16 (statin=7) pigs were analysed. Mean lesion length was 3.7 ± 0.8cm with a mean of 17.9 ± 5.7 lesion applications. Bi-directional conduction block was confirmed in 15/15 pigs (100%) at EPS1 and EPS2. Conclusions: Atorvastatin did not affect ablation lesion continuity in this pig atrial linear ablation model. If patients are on long-term statins for AF reduction, periablation cessation is probably not necessary.

Utilization of bio-oil for cooking and lighting

Among the available alternative sources of energy in Bangladesh bio-oil is recognized to be a promising alternative energy source. Bio-oil can be extracted by pyrolysis as well as expelling or solvent extractionmethod. In these days bio-oil is merely used in vehicles and power plants after some up gradation .However, it is not used for domestic purposes like cooking and lighting due to its high density and viscosity. This paper outlines the design of a gravity stove to use high dense and viscous bio-oil for cooking purpose. For this, Pongamia pinnata (karanj) oil extracted by solvent extraction method is used as fuel fed under gravity force. Efficiency of gravity stove with high dense and viscous bio-oil (karanj) is 11.81% which of kerosene stove is 17.80% also the discharge of karanj oil through gravity stove is sufficient for continuous burning. Thus, bio-oil can be effective replacement of kerosene for domestic purposes.

From 'Neighbours' to 'Packed to the Rafters': accounting for longevity in the evolution of Aussie soaps

If there is one television programming staple for which Australian television drama is known internationally, it is the long-running television soap, with Neighbours (originally produced by Grundy in 1985) lauded as 'the most outstanding example of Australian series export' (Cunningham and Jacka, 1996). Twenty-five years on, this program still airs on domestic and international TV schedules five days a week, despite waning popularity with local Australian audiences. Considering past interest in the success and longevity of this soap, it is apposite to look again at the continuing progress of Neighbours foremost as a global brand. In comparison, Packed to the Rafters is treated here as a contemporary version of familiar Aussie themes related to everyday middle-class suburbia, populated with blue skies and feel-good characters expressing wholesome family values, but with a stylistic innovation defined here as domestic realism. As part of the production ecology of the late 2000s, Packed to the Rafters demonstrates the considerable role for local drama productions as loss leaders and flagship programming for commercial free-to-air networks up against an increasingly difficult domestic market.

‘Argue with us!’: audience co-creation through post-performance discussions.

In this article Caroline Heim explores an avenue for the audience's contribution to the theatrical event that has emerged as increasingly important over the past decade: postperformance discussions. With the exception of theatres that actively encourage argument such as the Staatstheater Stuttgart, most extant audience discussions in Western mainstream theatres privilege the voice of the theatre expert. Caroline Heim presents case studies of post-performance discussions held after performances of Anne of the Thousand Days and Who's Afraid of Virginia Woolf? which trialled a new model of audience co-creation. An audience text which informs the theatrical event was created, and a new role, that of audience critic, established in the process.

Tear film surface quality with rigid and soft contact lenses

Objectives: To measure tear film surface quality (TFSQ) using dynamic high-speed videokeratoscopy during short-term (8 hours) use of rigid and soft contact lenses. Methods: A group of fourteen subjects wore 3 different types of contact lenses on 3 different non-consecutive days (order randomized) in one eye only. Subjects were screened to exclude those with dry eye. The lenses included a PMMA hard, an RGP (Boston XO) and a soft silicone hydrogel lens. Three 30 second long high speed videokeratoscopy recordings were taken with contact lenses in-situ, in the morning and again after 8 hours of contact lens wear, both in normal and suppressed blinking conditions. Recordings were also made on a baseline day with no contact lens wear. Results: The presence of a contact lens in the eye had a significant effect on the mean TFSQ in both natural and suppressed blinking conditions (p=0.001 and p=0.01 respectively, repeated measures ANOVA). TFSQ was worse with all the lenses compared to no lens in the eye (in the afternoon during both normal and suppressed blinking conditions (all p<0.05). In natural blinking conditions, the mean TFSQ for the PMMA and RGP lenses was significantly worse than the baseline day (no lens) for both morning and afternoon measures (p<0.05). Conclusions: This study shows that both rigid and soft contact lenses adversely affect the TFSQ in both natural and suppressed blinking conditions. No significant differences were found between the lens types and materials. Keywords: Tear film surface quality, rigid contact lens, soft contact lens, dynamic high-speed videokeratoscopy

Clinical utility of mental state screening as a predictor of intellectual outcomes 6 months after diagnosis of type 1 diabetes

Background Screening tests of basic cognitive status or ‘mental state’ have been shown to predict mortality and functional outcomes in adults. This study examined the relationship between mental state and outcomes in children with type 1 diabetes. Objective We aimed to determine whether mental state at diagnosis predicts longer term cognitive function of children with a new diagnosis of type 1 diabetes. Methods Mental state of 87 patients presenting with newly diagnosed type 1 diabetes was assessed using the School-Years Screening Test for the Evaluation of Mental Status. Cognitive abilities were assessed 1 wk and 6 months postdiagnosis using standardized tests of attention, memory, and intelligence. Results Thirty-seven children (42.5%) had reduced mental state at diagnosis. Children with impaired mental state had poorer attention and memory in the week following diagnosis, and, after controlling for possible confounding factors, significantly lower IQ at 6 months compared to those with unimpaired mental state (p < 0.05). Conclusions Cognition is impaired acutely in a significant number of children presenting with newly diagnosed type 1 diabetes. Mental state screening is an effective method of identifying children at risk of ongoing cognitive difficulties in the days and months following diagnosis. Clinicians may consider mental state screening for all newly diagnosed diabetic children to identify those at risk of cognitive sequelae.

Malnutrition and its impact on cost of hospitalization, length of stay, readmission and 3-year mortality

Background & aims: The confounding effect of disease on the outcomes of malnutrition using diagnosis-related groups (DRG) has never been studied in a multidisciplinary setting. This study aims to determine the prevalence of malnutrition in a tertiary hospital in Singapore and its impact on hospitalization outcomes and costs, controlling for DRG. Methods: This prospective cohort study included a matched case control study. Subjective Global Assessment was used to assess the nutritional status on admission of 818 adults. Hospitalization outcomes over 3 years were adjusted for gender, age, ethnicity, and matched for DRG. Results: Malnourished patients (29%) had longer hospital stays (6.9 ± 7.3 days vs. 4.6 ± 5.6 days, p < 0.001) and were more likely to be readmitted within 15 days (adjusted relative risk = 1.9, 95%CI 1.1–3.2, p = 0.025). Within a DRG, the mean difference between actual cost of hospitalization and the average cost for malnourished patients was greater than well-nourished patients (p = 0.014). Mortality was higher in malnourished patients at 1 year (34% vs. 4.1 %), 2 years (42.6% vs. 6.7%) and 3 years (48.5% vs. 9.9%); p < 0.001 for all. Overall, malnutrition was a significant predictor of mortality (adjusted hazard ratio = 4.4, 95% CI 3.3-6.0, p < 0.001). Conclusions: Malnutrition was evident in up to one third of the inpatients and led to poor hospitalization outcomes and survival as well as increased costs of care, even after matching for DRG. Strategies to prevent and treat malnutrition in the hospital and post-discharge are needed.

Ambient temperature and cardiorespiratory morbidity : a systematic review and meta-analysis

BACKGROUND: The effect of extreme temperature has become an increasing public health concern. Evaluating the impact of ambient temperature on morbidity has received less attention than its impact on mortality. METHODS: We performed a systematic literature review and extracted quantitative estimates of the effects of hot temperatures on cardiorespiratory morbidity. There were too few studies on effects of cold temperatures to warrant a summary. Pooled estimates of effects of heat were calculated using a Bayesian hierarchical approach that allowed multiple results to be included from the same study, particularly results at different latitudes and with varying lagged effects. RESULTS: Twenty-one studies were included in the final meta-analysis. The pooled results suggest an increase of 3.2% (95% posterior interval = -3.2% to 10.1%) in respiratory morbidity with 1°C increase on hot days. No apparent association was observed for cardiovascular morbidity (-0.5% [-3.0% to 2.1%]). The length of lags had inconsistent effects on the risk of respiratory and cardiovascular morbidity, whereas latitude had little effect on either. CONCLUSIONS: The effects of temperature on cardiorespiratory morbidity seemed to be smaller and more variable than previous findings related to mortality.

A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study

Background: Patients with chest pain contribute substantially to emergency department attendances, lengthy hospital stay, and inpatient admissions. A reliable, reproducible, and fast process to identify patients presenting with chest pain who have a low short-term risk of a major adverse cardiac event is needed to facilitate early discharge. We aimed to prospectively validate the safety of a predefined 2-h accelerated diagnostic protocol (ADP) to assess patients presenting to the emergency department with chest pain symptoms suggestive of acute coronary syndrome. Methods: This observational study was undertaken in 14 emergency departments in nine countries in the Asia-Pacific region, in patients aged 18 years and older with at least 5 min of chest pain. The ADP included use of a structured pre-test probability scoring method (Thrombolysis in Myocardial Infarction [TIMI] score), electrocardiograph, and point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin. The primary endpoint was major adverse cardiac events within 30 days after initial presentation (including initial hospital attendance). This trial is registered with the Australia-New Zealand Clinical Trials Registry, number ACTRN12609000283279. Findings: 3582 consecutive patients were recruited and completed 30-day follow-up. 421 (11•8%) patients had a major adverse cardiac event. The ADP classified 352 (9•8%) patients as low risk and potentially suitable for early discharge. A major adverse cardiac event occurred in three (0•9%) of these patients, giving the ADP a sensitivity of 99•3% (95% CI 97•9–99•8), a negative predictive value of 99•1% (97•3–99•8), and a specificity of 11•0% (10•0–12•2). Interpretation: This novel ADP identifies patients at very low risk of a short-term major adverse cardiac event who might be suitable for early discharge. Such an approach could be used to decrease the overall observation periods and admissions for chest pain. The components needed for the implementation of this strategy are widely available. The ADP has the potential to affect health-service delivery worldwide.

Exposure to hot and cold temperatures and ambulance attendances in Brisbane, Australia: A time series study

ABSTRACT Objectives: To investigate the effect of hot and cold temperatures on ambulance attendances. Design: An ecological time series study. Setting and participants: The study was conducted in Brisbane, Australia. We collected information on 783 935 daily ambulance attendances, along with data of associated meteorological variables and air pollutants, for the period of 2000–2007. Outcome measures: The total number of ambulance attendances was examined, along with those related to cardiovascular, respiratory and other non-traumatic conditions. Generalised additive models were used to assess the relationship between daily mean temperature and the number of ambulance attendances. Results: There were statistically significant relationships between mean temperature and ambulance attendances for all categories. Acute heat effects were found with a 1.17% (95% CI: 0.86%, 1.48%) increase in total attendances for 1 °C increase above threshold (0–1 days lag). Cold effects were delayed and longer lasting with a 1.30% (0.87%, 1.73%) increase in total attendances for a 1 °C decrease below the threshold (2–15 days lag). Harvesting was observed following initial acute periods of heat effects, but not for cold effects. Conclusions: This study shows that both hot and cold temperatures led to increases in ambulance attendances for different medical conditions. Our findings support the notion that ambulance attendance records are a valid and timely source of data for use in the development of local weather/health early warning systems.

Exposure to hot and cold temperatures and ambulance attendances in Brisbane, Australia

Objectives: To investigate the effect of hot and cold temperatures on ambulance attendances. Design: An ecological time series study. Setting and participants: The study was conducted in Brisbane, Australia. We collected information on 783 935 daily ambulance attendances, along with data of associated meteorological variables and air pollutants, for the period of 2000–2007. Outcome measures: The total number of ambulance attendances was examined, along with those related to cardiovascular, respiratory and other non-traumatic conditions. Generalised additive models were used to assess the relationship between daily mean temperature and the number of ambulance attendances. Results: There were statistically significant relationships between mean temperature and ambulance attendances for all categories. Acute heat effects were found with a 1.17% (95% CI: 0.86%, 1.48%) increase in total attendances for 1 °C increase above threshold (0–1 days lag). Cold effects were delayed and longer lasting with a 1.30% (0.87%, 1.73%) increase in total attendances for a 1 °C decrease below the threshold (2–15 days lag). Harvesting was observed following initial acute periods of heat effects, but not for cold effects. Conclusions: This study shows that both hot and cold temperatures led to increases in ambulance attendances for different medical conditions. Our findings support the notion that ambulance attendance records are a valid and timely source of data for use in the development of local weather/health early warning systems.

A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone/periodontal ligament complex

This study describes the design of a biphasic scaffold composed of a Fused Deposition Modeling scaffold (bone compartment) and an electrospun membrane (periodontal compartment) for periodontal regeneration. In order to achieve simultaneous alveolar bone and periodontal ligament regeneration a cell-based strategy was carried out by combining osteoblast culture in the bone compartment and placement of multiple periodontal ligament (PDL) cell sheets on the electrospun membrane. In vitro data showed that the osteoblasts formed mineralized matrix in the bone compartment after 21 days in culture and that the PDL cell sheet harvesting did not induce significant cell death. The cell-seeded biphasic scaffolds were placed onto a dentin block and implanted for 8 weeks in an athymic rat subcutaneous model. The scaffolds were analyzed by μCT, immunohistochemistry and histology. In the bone compartment, a more intense ALP staining was obtained following seeding with osteoblasts, confirming the μCT results which showed higher mineralization density for these scaffolds. A thin mineralized cementum-like tissue was deposited on the dentin surface for the scaffolds incorporating the multiple PDL cell sheets, as observed by H&E and Azan staining. These scaffolds also demonstrated better attachment onto the dentin surface compared to no attachment when no cell sheets were used. In addition, immunohistochemistry revealed the presence of CEMP1 protein at the interface with the dentine. These results demonstrated that the combination of multiple PDL cell sheets and a biphasic scaffold allows the simultaneous delivery of the cells necessary for in vivo regeneration of alveolar bone, periodontal ligament and cementum. © 2012 Elsevier Ltd.

Ureaplasma parvum : understanding the complexities of intra-amniotic infection in an ovine model

The human Ureaplasma species are the most frequently isolated bacteria from the upper genital tract of pregnant women and can cause clinically asymptomatic, intra-uterine infections, which are difficult to treat with antimicrobials. Ureaplasma infection of the upper genital tract during pregnancy has been associated with numerous adverse outcomes including preterm birth, chorioamnionitis and neonatal respiratory diseases. The mechanisms by which ureaplasmas are able to chronically colonise the amniotic fluid and avoid eradication by (i) the host immune response and (ii) maternally-administered antimicrobials, remain virtually unexplored. To address this gap within the literature, this study investigated potential mechanisms by which ureaplasmas are able to cause chronic, intra-amniotic infections in an established ovine model. In this PhD program of research the effectiveness of standard, maternal erythromycin for the treatment of chronic, intra-amniotic ureaplasma infections was evaluated. At 55 days of gestation pregnant ewes received an intra-amniotic injection of either: a clinical Ureaplasma parvum serovar 3 isolate that was sensitive to macrolide antibiotics (n = 16); or 10B medium (n = 16). At 100 days of gestation, ewes were then randomised to receive either maternal erythromycin treatment (30 mg/kg/day for four days) or no treatment. Ureaplasmas were isolated from amniotic fluid, chorioamnion, umbilical cord and fetal lung specimens, which were collected at the time of preterm delivery of the fetus (125 days of gestation). Surprisingly, the numbers of ureaplasmas colonising the amniotic fluid and fetal tissues were not different between experimentally-infected animals that received erythromycin treatment or infected animals that did not receive treatment (p > 0.05), nor were there any differences in fetal inflammation and histological chorioamnionitis between these groups (p > 0.05). These data demonstrate the inability of maternal erythromycin to eradicate intra-uterine ureaplasma infections. Erythromycin was detected in the amniotic fluid of animals that received antimicrobial treatment (but not in those that did not receive treatment) by liquid chromatography-mass spectrometry; however, the concentrations were below therapeutic levels (<10 – 76 ng/mL). These findings indicate that the ineffectiveness of standard, maternal erythromycin treatment of intra-amniotic ureaplasma infections may be due to the poor placental transfer of this drug. Subsequently, the phenotypic and genotypic characteristics of ureaplasmas isolated from the amniotic fluid and chorioamnion of pregnant sheep after chronic, intra-amniotic infection and low-level exposure to erythromycin were investigated. At 55 days of gestation twelve pregnant ewes received an intra-amniotic injection of a clinical U. parvum serovar 3 isolate, which was sensitive to macrolide antibiotics. At 100 days of gestation, ewes received standard maternal erythromycin treatment (30 mg/kg/day for four days, n = 6) or saline (n = 6). Preterm fetuses were surgically delivered at 125 days of gestation and ureaplasmas were cultured from the amniotic fluid and the chorioamnion. The minimum inhibitory concentrations (MICs) of erythromycin, azithromycin and roxithromycin were determined for cultured ureaplasma isolates, and antimicrobial susceptibilities were different between ureaplasmas isolated from the amniotic fluid (MIC range = 0.08 – 1.0 mg/L) and chorioamnion (MIC range = 0.06 – 5.33 mg/L). However, the increased resistance to macrolide antibiotics observed in chorioamnion ureaplasma isolates occurred independently of exposure to erythromycin in vivo. Remarkably, domain V of the 23S ribosomal RNA gene (which is the target site of macrolide antimicrobials) of chorioamnion ureaplasmas demonstrated significant variability (125 polymorphisms out of 422 sequenced nucleotides, 29.6%) when compared to the amniotic fluid ureaplasma isolates and the inoculum strain. This sequence variability did not occur as a consequence of exposure to erythromycin, as the nucleotide substitutions were identical between chorioamnion ureaplasmas isolated from different animals, including those that did not receive erythromycin treatment. We propose that these mosaic-like 23S ribosomal RNA gene sequences may represent gene fragments transferred via horizontal gene transfer. The significant differences observed in (i) susceptibility to macrolide antimicrobials and (ii) 23S ribosomal RNA sequences of ureaplasmas isolated from the amniotic fluid and chorioamnion suggests that the anatomical site from which they were isolated may exert selective pressures that alter the socio-microbiological structure of the bacterial population, by selecting for genetic changes and altered antimicrobial susceptibility profiles. The final experiment for this PhD examined antigenic size variation of the multiple banded antigen (MBA, a surface-exposed lipoprotein and predicted ureaplasmal virulence factor) in chronic, intra-amniotic ureaplasma infections. Previously defined ‘virulent-derived’ and ‘avirulent-derived’ clonal U. parvum serovar 6 isolates (each expressing a single MBA protein) were injected into the amniotic fluid of pregnant ewes (n = 20) at 55 days of gestation, and amniotic fluid was collected by amniocentesis every two weeks until the time of near-term delivery of the fetus (at 140 days of gestation). Both the avirulent and virulent clonal ureaplasma strains generated MBA size variants (ranging in size from 32 – 170 kDa) within the amniotic fluid of pregnant ewes. The mean number of MBA size variants produced within the amniotic fluid was not different between the virulent (mean = 4.2 MBA variants) and avirulent (mean = 4.6 MBA variants) ureaplasma strains (p = 0.87). Intra-amniotic infection with the virulent strain was significantly associated with the presence of meconium-stained amniotic fluid (p = 0.01), which is an indicator of fetal distress in utero. However, the severity of histological chorioamnionitis was not different between the avirulent and virulent groups. We demonstrated that ureaplasmas were able to persist within the amniotic fluid of pregnant sheep for 85 days, despite the host mounting an innate and adaptive immune response. Pro-inflammatory cytokines (interleukin (IL)-1â, IL-6 and IL-8) were elevated within the chorioamnion tissue of pregnant sheep from both the avirulent and virulent treatment groups, and this was significantly associated with the production of anti-ureaplasma IgG antibodies within maternal sera (p < 0.05). These findings suggested that the inability of the host immune response to eradicate ureaplasmas from the amniotic cavity may be due to continual size variation of MBA surface-exposed epitopes. Taken together, these data confirm that ureaplasmas are able to cause long-term in utero infections in a sheep model, despite standard antimicrobial treatment and the development of a host immune response. The overall findings of this PhD project suggest that ureaplasmas are able to cause chronic, intra-amniotic infections due to (i) the limited placental transfer of erythromycin, which prevents the accumulation of therapeutic concentrations within the amniotic fluid; (ii) the ability of ureaplasmas to undergo rapid selection and genetic variation in vivo, resulting in ureaplasma isolates with variable MICs to macrolide antimicrobials colonising the amniotic fluid and chorioamnion; and (iii) antigenic size variation of the MBA, which may prevent eradication of ureaplasmas by the host immune response and account for differences in neonatal outcomes. The outcomes of this program of study have improved our understanding of the biology and pathogenesis of this highly adapted microorganism.