Microbial colonisation of human follicular fluid and adverse in vitro fertilisation outcomes

This study, investigating 263 women undergoing trans-vaginal oocyte retrieval for in vitro fertilisation (IVF) found that microorganisms colonising follicular fluid contributed to adverse IVF (pre-implantation) and pregnancy (post-implantation) outcomes including poor quality embryos, failed pregnancy and early pregnancy loss (< 37 weeks gestation). Some microorganisms also showed in vitro growth patterns in liquid media that appeared to be enhanced by the hormonal stimulation protocol used for oocyte retrieval. Elaborated cytokines within follicular fluid were also associated with adverse IVF outcomes. This study is imperative because infertility affects 16% of the human population and the numbers of couples needing assistance continues to increase. Despite significant improvements in the technical aspects of assisted reproductive technologies (ART), the live birth rate has not increased proportionally. Overt genital tract infection has been associated with both infertility and adverse pregnancy outcomes (including miscarriage and preterm birth) as a direct result of the infection or the host response to it. Importantly, once inflammation had become established, medical treatment often failed to prevent these significant adverse outcomes. Current evaluations of fertility focus on the ovary as a site of steroid hormone production and ovulation. However, infertility as a result of subclinical colonisation of the ovary has not been reported. Furthermore, identification of the microorganisms present in follicular fluid and the local cytokine profile may provide clinicians with an early indication of the prognosis for IVF treatment in infertile couples, thus allowing antimicrobial treatment and/or counselling about possible IVF failure. During an IVF cycle, multiple oocytes undergo maturation in vivo in response to hormonal hyperstimulation. Oocytes for in vitro insemination are collected trans-vaginally. The follicular fluid that bathes the maturing oocyte in vivo, usually is discarded as part of the IVF procedure, but provides a unique opportunity to investigate microbial causes of adverse IVF outcomes. Some previous studies have identified follicular fluid markers that predict IVF pregnancy outcomes. However, there have not been any detailed microbiological studies of follicular fluid. For this current study, paired follicular fluid and vaginal secretion samples were collected from women undergoing IVF cycles to determine whether microorganisms in follicular fluid were associated with adverse IVF outcomes. Microorganisms in follicular fluid were regarded as either "colonisers" or "contaminants"; colonisers, if they were unique to the follicular fluid sample, and contaminants if the same microorganisms were detected in the vaginal and follicular fluid samples indicating that the follicular fluid was merely contaminated during the oocyte retrieval process. Quite unexpectedly, by these criteria, we found that follicular fluid from approximately 30% of all subjects was colonised with bacteria. Fertile and infertile women with colonised follicular fluid had decreased embryo transfer rates and decreased pregnancy rates compared to women with contaminated follicular fluids. The observation that follicular fluid was not always sterile, but contained a diverse range of microorganisms, is novel. Many of the microorganisms we detected in follicular fluid are known opportunistic pathogens that have been detected in upper genital tract infections and are associated with adverse pregnancy outcomes. Bacteria were able to survive for at least 28 weeks in vitro, in cultures of follicular fluid. Within 10 days of establishing these in vitro cultures, several species (Lactobacillus spp., Bifidobacterium spp., Propionibacterium spp., Streptococcus spp. and Salmonella entericus) had formed biofilms. Biofilms play a major role in microbial pathogenicity and persistence. The propensity of microbial species to form biofilms in follicular fluid suggests that successful treatment of these infections with antimicrobials may be difficult. Bifidobacterium spp. grew, in liquid media, only if concentrations of oestradiol and progesterone were similar to those achieved in vivo during an IVF cycle. In contrast, the growth of Streptococcus agalactiae and Escherichia coli was inhibited or abolished by the addition of these hormones to culture medium. These data suggest that the likelihood of microorganisms colonising follicular fluid and the species of bacteria involved is influenced by the stage of the menstrual cycle and, in the case of IVF, the nature and dose of steroid hormones administered for the maturation of multiple oocytes in vivo. Our findings indicate that the elevated levels of steroid hormones during an IVF cycle may influence the microbial growth within follicular fluid, suggesting that the treatment itself will impact on the microflora present in the female upper genital tract during pre-conception and early post-conception phases of the cycle. The effect of the host immune response on colonising bacteria and on the outcomes of IVF also was investigated. White blood cells reportedly compose between 5% and 15% of the cell population in follicular fluid. The follicular membrane is semi-permeable and cells are actively recruited as part of the normal menstrual cycle and in response to microorganisms. A previous study investigated follicular fluid cytokines from infertile women and fertile oocyte donors undergoing IVF, and concluded that there were no significant differences in the cytokine concentrations between the two groups. However, other studies have reported differences in the follicular fluid cytokine levels associated with infertile women with endometriosis or polycystic ovary syndrome. In this study, elevated levels of interleukin (IL)-1 á, IL-1 â and vascular endothelial growth factor (VEGF) in vaginal fluid were associated with successful fertilisation, which may be useful marker for successful fertilisation outcomes for women trying to conceive naturally or prior to oocyte retrieval for IVF. Elevated levels of IL-6, IL-12p40, granulocyte colony stimulating factor (GCSF) and interferon-gamma (IFN ã) in follicular fluid were associated with successful embryo transfer. Elevated levels of pro-inflammatory IL-18 and decreased levels of anti-inflammatory IL-10 were identified in follicular fluid from women with idiopathic infertility. Successful fertilisation and implantation is dependent on a controlled pro-inflammatory environment, involving active recruitment of pro-inflammatory mediators to the genital tract as part of the menstrual cycle and early pregnancy. However, ongoing pregnancy requires an enhanced anti-inflammatory environment to ensure that the maternal immune system does not reject the semi-allergenic foetus. The pro-inflammatory skew in the follicular fluid of women with idiopathic infertility, correlates with normal rates of fertilisation, embryo discard and embryo transfer, observed for this cohort, which were similar to the outcomes observed for fertile women. However, their pregnancy rate was reduced compared to fertile women. An altered local immune response in follicular fluid may provide a means of explaining infertility in this cohort, previously defined as 'idiopathic'. This study has found that microorganisms colonising follicular fluid may have contributed to adverse IVF and pregnancy outcomes. Follicular fluid bathes the cumulus oocyte complex during the in vivo maturation process, and microorganisms in the fluid, their metabolic products or the local immune response to these microorganisms may result in damage to the oocytes, degradation of the cumulus or contamination of the IVF culture system. Previous studies that have discounted bacterial contamination of follicular fluid as a cause of adverse IVF outcomes failed to distinguish between bacteria that were introduced into the follicular fluid at the time of trans-vaginal oocyte retrieval and those that colonised the follicular fluid. Those bacteria that had colonised the fluid may have had time to form biofilms and to elicit a local immune response. Failure to draw this distinction has previously prevented consideration of bacterial colonisation of follicular fluid as a cause of adverse IVF outcomes. Several observations arising from this study are of significance to IVF programs. Follicular fluid is not always sterile and colonisation of follicular fluid is a cause of adverse IVF and pregnancy outcomes. Hormonal stimulation associated with IVF may influence whether follicular fluid is colonised and enhance the growth of specific species of bacteria within follicular fluid. Bacteria in follicular fluid may form biofilms and literature has reported that this may influence their susceptibility to antibiotics. Monitoring the levels of selected cytokines within vaginal secretions may inform fertilisation outcomes. This study has identified novel factors contributing to adverse IVF outcomes and that are most likely to affect also natural conception outcomes. Early intervention, possibly using antimicrobial or immunological therapies may reduce the need for ART and improve reproductive health outcomes for all women.

Cyberinfrastructure inside out : definition and influences shaping its emergence, development, and implementation in the early 21st century

The authors provide a theoretically generative definition of cyberinfrastructure (CI) by drawing from existing definitions and literature in social sciences, law, and policy studies. They propose two models of domestic and international influencers on CI emergence, development, and implementation in the early 21st century. Based on its historical emergence and computational power, they argue that cyberinfrastructure is built on, and yet distinct from the current notion of the internet. The authors seek to answer two research questions: firstly, what is cyberinfrastructure? And secondly, what national and international influencers shape its emergence, development and implementation (in e-science) in the early 21st century? Additionally, consideration will be given to the implications of the proposed definition and models, and future directions on CI research in Internet studies will be suggested.

The use of virtual prototyping for hazard identification in the early design stage

Purpose: The construction industry is well known for its high accident rate and many practitioners consider a preventative approach to be the most important means of bringing about improvements. This paper addresses previous research and the weaknesses of existing preventative approaches and a new application is described and illustrated involving the use of a multi-dimensional simulation tool - Construction Virtual Prototyping (CVP). Methodology: A literature review was conducted to investigate previous studies of hazard identification and safety management and to develop the new approach. Due to weaknesses in current practice, the research study explored the use of computer simulation techniques to create virtual environments where users can explore and identify construction hazards. Specifically, virtual prototyping technology was deployed to develop typical construction scenarios in which unsafe or hazardous incidents occur. In a case study, the users’ performance was evaluated their responses to incidents within the virtual environment and the effectiveness of the computer simulation system established though interviews with the safety project management team. Findings: The opinions and suggestions provided by the interviewees led to the initial conclusion that the simulation tool was useful in assisting the safety management team’s hazard identification process during the early design stage. Originality: The research introduces an innovative method to support the management teams’ reviews of construction site safety. The system utilises three-dimensional modelling and four-dimensional simulation of worker behaviour, a configuration that has previously not been employed in construction simulations. An illustration of the method’s use is also provided, together with a consideration of its strengths and weaknesses.

Early local functional changes in the human diabetic retina : a global flash multifocal electroretinogram study

Purpose: To investigate early functional changes of local retinal defects in type II diabetic patients using the global flash multifocal electroretinogram (MOFO mfERG). Methods: Thirty-eight diabetic patients and 14 age-matched controls were recruited. Nine of the diabetics were free from diabetic retinopathy (DR), while the remainder had mild to moderate non-proliferative diabetic retinopathy. The MOFO mfERG was performed at high (98%) and low (46%) contrast levels. MfERG responses were grouped into 35 regions for comparison with DR classification at those locations. Z-scores of the regional mfERG responses were compared across different types of DR defects. Results: The mfERG waveform consisted of the direct component (DC) and the induced component (IC). Local reduction in DC and IC amplitudes were found in diabetic patients with and without DR. With increasing severity of retinopathy, there was a further deterioration in amplitude of both components. Under MOFO mfERG paradigm, amplitude was a useful screening parameter. Conclusion: The MOFO mfERG can help in detecting early functional anomalies before the appearance of visible signs, and may assist in monitoring further functional deterioration in diabetic patients.

Accuracy of rate estimation using relaxed-clock models with a critical focus on the early metazoan radiation

In recent years, a number of phylogenetic methods have been developed for estimating molecular rates and divergence dates under models that relax the molecular clock constraint by allowing rate change throughout the tree. These methods are being used with increasing frequency, but there have been few studies into their accuracy. We tested the accuracy of several relaxed-clock methods (penalized likelihood and Bayesian inference using various models of rate change) using nucleotide sequences simulated on a nine-taxon tree. When the sequences evolved with a constant rate, the methods were able to infer rates accurately, but estimates were more precise when a molecular clock was assumed. When the sequences evolved under a model of autocorrelated rate change, rates were accurately estimated using penalized likelihood and by Bayesian inference using lognormal and exponential models of rate change, while other models did not perform as well. When the sequences evolved under a model of uncorrelated rate change, only Bayesian inference using an exponential rate model performed well. Collectively, the results provide a strong recommendation for using the exponential model of rate change if a conservative approach to divergence time estimation is required. A case study is presented in which we use a simulation-based approach to examine the hypothesis of elevated rates in the Cambrian period, and it is found that these high rate estimates might be an artifact of the rate estimation method. If this bias is present, then the ages of metazoan divergences would be systematically underestimated. The results of this study have implications for studies of molecular rates and divergence dates.

A genealogy of calculations at an early Queensland sugar mill

This study of a unique historic situation is sociologically framed and politically contextualized. It examines the technical and persuasive rhetorical dimensions of calculations employed at a nineteenth-century Queensland sugar plantation and mill in relation to the employment of indentured labour. Historical archival data is interpreted through the lens of the rhetoric of rationality. Queensland legislation permitted the employment of indentured Pacific islanders to assist in the development of its sugar industry. Accounting practices employed at the Colonial Sugar Refinery (CSR) Company’s Goondi Plantation and Mill focused on recording and controlling labour costs to maximize profits and maintain a healthy dividend to shareholders. The use of this single perspective, while it provides a restricted interpretation of events, nevertheless enables some unique insights about the practice of accounting in this historic context.

Australian children with special health care needs: Social-emotional and learning competencies in the early years

This study examined the relationship between special health care needs and social-emotional and learning competence in the early years, reporting on two waves of data from the Kindergarten Cohort of Growing up in Australia: The Longitudinal Study of Australian Children (LSAC). Six hundred and fifty children were identified through the 2-question Special Health Care Needs Screener as having special health care needs. Children with special health care needs were more likely to be male, to have been of low birth weight, to be taking prescription medications, to be diagnosed with a specific health condition and to be from families where the mother was less well educated. These children scored significantly lower on teacher-rated social-emotional and learning competencies prior to school compared to a control group of children without special health care needs. Multiple regression analyses indicated that being identified with a special health care need prior to school predicted lower social-emotional and learning competencies in the early years of school. Results are discussed in terms of the implications for policy and practice.

Resourcing Early Learners : New Networks, New Actors

The landscape of early childhood education and care is changing. Governments world-wide are assuming increasing authority in relation to child-rearing in the years before school entry, beyond the traditional role in assisting parents to do the best they can by their children. As part of a social agenda aimed at forming citizens well prepared to play an active part in a globalised knowledge economy, the idea of ‘early learning’ expresses the necessity of engaging caregivers right from the start of children’s lives. Nichols, Rowsell, Rainbird, and Nixon investigate this trend over three years, in two countries, and three contrasting regions, by setting themselves the task of tracing every service and agent offering resources under the banner of early learning. Far from a dry catalogue, the study involves in-depth ethnographic research in fascinating spaces such as a church-run centre for African refugee women and children, a state-of-the-art community library and an Australian country town. Included is an unprecedented inventory of an entire suburban mall. Richly visually documented, the study employs emerging methods such as Google-mapping to trace the travels of actual parents as they search for particular resources. Each chapter features a context investigated in this large, international study: the library, the mall, the clinic, and the church. The author team unravels new spaces and new networks at work in early childhood literacy and development.

Fashion, the body and technology : tracing early 20th century techno-utopian ideas, aesthetics and impulses in 21st century wearable technology

‘Wearable technology’, or the use of specialist technology in garments, is promoted by the electronics industry as the next frontier of fashion. However the story of wearable technology’s relationship with fashion begins neither with the development of miniaturised computers in the 1970s nor with sophisticated ‘smart textiles’ of the twenty-first century, despite what much of the rhetoric suggests. This study examines wearable technology against a longer history of fashion, highlighted by the influential techno-sartorial experiments of a group of early twentieth century avant-gardes including Italian Futurists Giacomo Balla and F.T. Marinetti, Russian Constructivists Varvara Stepanova and Liubov Popova, and Paris-based Cubist, Sonia Delaunay. Through the interdisciplinary framework of fashion studies, the thesis provides a fuller picture of wearable technology framed by the idea of utopia. Using comparative analysis, and applying the theoretical formulations of Fredric Jameson, Louis Marin and Michael Carter, the thesis traces the appearance of three techno-utopian themes from their origins in the machine age experiments of Balla, Marinetti, Stepanova, Popova and Delaunay to their twenty-first century reappearance in a dozen wearable technology projects. By exploring the central thesis that contemporary wearable technology resurrects the techno-utopian ideas and expressions of the early twentieth century, the study concludes that the abiding utopian impetus to embed technology in the aesthetics (prints, silhouettes, and fabrication) and functionality of fashion is to unify subject, society and environment under a totalising technological order.

Exploring antecedent factors in (Queensland) secondary school teachers’ early retirement intentions

Mature-age secondary teachers offer teaching a wealth of knowledge and skills that can contribute greatly to the quality of education. However, as with the greater workforce, there is an increasing trend for mature-age teachers to elect to retire early or to move into other work. Despite studies suggesting that teachers may be negatively affected by stress, there has been no research into the attitudes of mature-age teachers relating to early retirement and whether these or other factors are instrumental in their decision to retire from teaching. There is, however, a broad range of studies, commentary and analyses on ageing and work that can be utilised to develop a powerful analytical framework to identify the factors that can potentially influence the decision to take early retirement. This study examined the antecedent factors which influenced the early retirement decisions in 16 Queensland secondary school teachers. This study examined factors relating to the teachers decision to retire early and explored school and other factors relating to their decision. In addition, differences between urban and rural secondary school teachers were examined. Given the potentially complex nature of teachers. retirement decisions, the study utilised a qualitative approach. The study found that retired secondary teachers are confronted by ageing realities that are not responded to adequately by the education system, and participants expressed a general dissatisfaction with aspects of school management, especially as it related to bullying and non-inclusion in teaching-related decision making. This study also identified organisational issues within Education Queensland which contributed to system failures that affected mature-age teachers that need to be addressed. This study is one of the first studies to explore the factors influencing early retirement decisions in teachers. The implications of these factors on policy for Education Queensland and for workplace policies in general are discussed.

Incipient neurovulnerability and neuroprotection in early psychosis : a proton spectroscopy study of the anterior hippocampus at 3Tesla

Programmed cell death (PCD) and progenitor cell generation (of glial and in some brain areas also neuronal fate) in the CNS is an active process throughout life and is generally not associated with gliosis which means that PCD can be pathologically silent. The striking discovery that progenitor cell generation (of glial and in some brain areas neuronal fate) is widespread in the adult CNS (especially the hippocampus) suggest a much more dynamic scenario than previously thought and transcends the dichotomy between neurodevelopmental and neurodegenerative models of schizophrenia and related disorders. We suggest that the regulatory processes that control the regulation of PCD and the generation of progenitor cells may be disturbed in the early phase of psychotic disorders underpinning a disconnectivity syndrom at the onset of clinically overt disorders. An ongoing 1H-MRS study of the anterior hippocampus at 3 Tesla in mostly drug-naive first-episode psychosis patients suggests no change in NAA, but significant increases in myo-inositol and lactate. The data suggests that neuronal integrity in the anterior hippocampus is still intact at the early stage of illness or mainly only functionally impaired. However the increase in lactate and myo-inositol may reflect a potential disturbance of generation and PCD of progenitor cells (of glial and in selected brain areas also neuronal fate) at the onset of psychosis. If true the use of neuroprotective agents such as lithium or eicosapentaenoic acid (which inhibit PCD and support cell generation)in the early phase of psychotic disorders may be a potent treatment avenue to explore.

Jury option needs early verdict

The decision in Rubin v Buchanan [2011] QSC 275 confirms that a trial by jury should be considered at the outset of a proceeding.

Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription

Early HIV-1 reverse transcription can be separated into initiation and elongation phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(−)ssDNA] synthesis in intact virus, that different reverse transcriptase (RT) inhibitors affect distinct phases of early natural endogenous reverse transcription (NERT). The effects of nevirapine on NERT were consistent with a mechanism of action including both specific and nonspecific binding events. The nonspecific component of this inhibition targeted the elongation reaction, whereas the specific effect seemed principally to be directed at very early events (initiation or the initiation-elongation switch). In contrast, foscarnet and the nucleoside analog ddATP inhibited both early and late (−)ssDNA synthesis in a similar manner. We also examined compounds that targeted other viral proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an integrase inhibitor) also directly inhibited RT. Our results indicate that NERT can be used to identify and evaluate compounds that directly target the reverse transcription complex.

It’s always a pleasure : exploring productivity and pleasure in a writing group for early career academics

The professional development needs of early career academics (ECAs) are increasingly subject to scrutiny. The literature notes writing groups can be successful in increasing research outputs and improving research track records – a core concern for ECAs. However, the pressure on ECAs to publish takes the pleasure out of writing for many. We argue writing groups, created by and for ECAs, can provide an environment for ECAs to (re)produce pleasure in writing and participation in the processes of academic review and debate. In addition, our experience of a writing group was that it provided a platform of social and emotional support contributing to our personal well-being and professional development.

Indications for early hip revision surgery in the UK : A re-analysis of NJR data

This study determined the rate and indication for revision between cemented, uncemented, hybrid and resurfacing groups from NJR (6 th edition) data. Data validity was determined by interrogating for episodes of misclassification. We identified 6,034 (2.7%) misclassified episodes, containing 97 (4.3%) revisions. Kaplan-Meier revision rates at 3 years were 0.9% cemented, 1.9% for uncemented, 1.2% for hybrids and 3.0% for resurfacings (significant difference across all groups, p<0.001, with identical pattern in patients <55 years). Regression analysis indicated both prosthesis group and age significantly influenced failure (p<0.001). Revision for pain, aseptic loosening, and malalignment were highest in uncemented and resurfacing arthroplasty. Revision for dislocation was highest in uncemented hips (significant difference between groups, p<0.001). Feedback to the NJR on data misclassification has been made for future analysis. © 2012 Wichtig Editore.