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.

Acoustic emission for diesel engine monitoring: A review and preliminary

Vibration analysis has been a prime tool in condition monitoring of rotating machines, however, its application to internal combustion engines remains a challenge because engine vibration signatures are highly non-stationary that are not suitable for popular spectrum-based analysis. Signal-to-noise ratio is a main concern in engine signature analysis due to severe background noise being generated by consecutive mechanical events, such as combustion, valve opening and closing, especially in multi-cylinder engines. Acoustic Emission (AE) has been found to give excellent signal-to-noise ratio allowing discrimination of fine detail of normal or abnormal events during a given cycle. AE has been used to detect faults, such as exhaust valve leakage, fuel injection behaviour, and aspects of the combustion process. This paper presents a review of AE application to diesel engine monitoring and preliminary investigation of AE signature measured on an 18-cylinder diesel engine. AE is compared with vibration acceleration for varying operating conditions: load and speed. Frequency characteristics of AE from those events are analysed in time-frequency domain via short time Fourier trasform. The result shows a great potential of AE analysis for detection of various defects in diesel engines.

Time limitations in NAPLAN numeracy tests

The article discusses evidence that time prevented many students from showing what they could do in the 2010 Year 7 and 9 NAPLAN numeracy tests. In addition to analysing the available data, the article discusses some NAPLAN numeracy questions that contribute to this problem. It is suggested that schools should investigate whether time limitation is a problem for their own students. The article discusses the implications of these findings for teachers preparing students for NAPLAN tests and for the developers of the tests.

Change Point Estimation in Monitoring Survival Time

Precise identification of the time when a change in a hospital outcome has occurred enables clinical experts to search for a potential special cause more effectively. In this paper, we develop change point estimation methods for survival time of a clinical procedure in the presence of patient mix in a Bayesian framework. We apply Bayesian hierarchical models to formulate the change point where there exists a step change in the mean survival time of patients who underwent cardiac surgery. The data are right censored since the monitoring is conducted over a limited follow-up period. We capture the effect of risk factors prior to the surgery using a Weibull accelerated failure time regression model. Markov Chain Monte Carlo is used to obtain posterior distributions of the change point parameters including location and magnitude of changes and also corresponding probabilistic intervals and inferences. The performance of the Bayesian estimator is investigated through simulations and the result shows that precise estimates can be obtained when they are used in conjunction with the risk-adjusted survival time CUSUM control charts for different magnitude scenarios. The proposed estimator shows a better performance where a longer follow-up period, censoring time, is applied. In comparison with the alternative built-in CUSUM estimator, more accurate and precise estimates are obtained by the Bayesian estimator. These superiorities are enhanced when probability quantification, flexibility and generalizability of the Bayesian change point detection model are also considered.

Critical time scales for advection–diffusion–reaction processes

The concept of local accumulation time (LAT) was introduced by Berezhkovskii and coworkers in 2010–2011 to give a finite measure of the time required for the transient solution of a reaction–diffusion equation to approach the steady–state solution (Biophys J. 99, L59 (2010); Phys Rev E. 83, 051906 (2011)). Such a measure is referred to as a critical time. Here, we show that LAT is, in fact, identical to the concept of mean action time (MAT) that was first introduced by McNabb in 1991 (IMA J Appl Math. 47, 193 (1991)). Although McNabb’s initial argument was motivated by considering the mean particle lifetime (MPLT) for a linear death process, he applied the ideas to study diffusion. We extend the work of these authors by deriving expressions for the MAT for a general one–dimensional linear advection–diffusion–reaction problem. Using a combination of continuum and discrete approaches, we show that MAT and MPLT are equivalent for certain uniform–to-uniform transitions; these results provide a practical interpretation for MAT, by directly linking the stochastic microscopic processes to a meaningful macroscopic timescale. We find that for more general transitions, the equivalence between MAT and MPLT does not hold. Unlike other critical time definitions, we show that it is possible to evaluate the MAT without solving the underlying partial differential equation (pde). This makes MAT a simple and attractive quantity for practical situations. Finally, our work explores the accuracy of certain approximations derived using the MAT, showing that useful approximations for nonlinear kinetic processes can be obtained, again without treating the governing pde directly.

Driver response time of queuing vehicles at urban signalized intersections

Driver response (reaction) time (tr) of the second queuing vehicle is generally longer than other vehicles at signalized intersections. Though this phenomenon was revealed in 1972, the above factor is still ignored in conventional departure models. This paper highlights the need for quantitative measurements and analysis of queuing vehicle performance in spontaneous discharge pattern because it can improve microsimulation. Video recording from major cities in Australia plus twenty two sets of vehicle trajectories extracted from the Next Generation Simulation (NGSIM) Peachtree Street Dataset have been analyzed to better understand queuing vehicle performance in the discharge process. Findings from this research will alleviate driver response time and also can be used for the calibration of the microscopic traffic simulation model.

Benefits and issues of urban network travel time prediction

This paper presents the benefits and issues related to travel time prediction on urban network. Travel time information quantifies congestion and is perhaps the most important network performance measure. Travel time prediction has been an active area of research for the last five decades. The activities related to ITS have increased the attention of researchers for better and accurate real-time prediction of travel time. Majority of the literature on travel time prediction is applicable to freeways where, under non-incident conditions, traffic flow is not affected by external factors such as traffic control signals and opposing traffic flows. On urban environment the problem is more complicated due to conflicting areas (intersections), mid-link sources and sinks etc. and needs to be addressed.

Field portable time resolved SORS sensor for the identification of concealed hazards

Raman spectroscopy, when used in spatially offset mode, has become a potential tool for the identification of explosives and other hazardous substances concealed in opaque containers. The molecular fingerprinting capability of Raman spectroscopy makes it an attractive tool for the unambiguous identification of hazardous substances in the field. Additionally, minimal sample preparation is required compared with other techniques. We report a field portable time resolved Raman sensor for the detection of concealed chemical hazards in opaque containers. The new sensor uses a pulsed nanosecond laser source in conjunction with an intensified CCD detector. The new sensor employs a combination of time and space resolved Raman spectroscopy to enhance the detection capability. The new sensor can identify concealed hazards by a single measurement without any chemometric data treatments.

The NetWorkPlace(TM) Phenomenon: any time and any place - reality or a seductive myth?

A new spatial logic encompassing redefined concepts of time and place, space and distance, requires a comprehensive shift in the approach to designing workplace environments for today’s adaptive, collaborative organizations operating in a dynamic business world. Together with substantial economic and cultural shifts and an increased emphasis on lifestyle considerations, the advances in information technology have prompted a radical re-ordering of organizational relationships and the associated structures, processes, and places of doing business. Within the duality of space and an augmentation of the traditional notions of place, organizational and institutional structures pose new challenges for the design professions. The literature reveals that there has always been a mono-organizational focus in relation to workplace design strategies and the burgeoning trend towards inter-organizational collaboration, enabled the identification of a gap in the knowledge relative to workplace design. The NetWorkPlaceTM© constitutes a multi-dimensional concept having the capacity to deal with the fluidity and ambiguity characteristic of the network context, as both a topic of research and the way of going about it.

Public participation in infrastructure and construction projects in China: From an EIA-based to a whole-cycle process

Many governments world-wide are increasingly encouraging the involvement of interested individuals, groups and organisations in their publicinfrastructure and construction (PIC) projects as a means of improving the openness, transparency and accountability of the decision-making process and help improve the projects’ long-term viability and benefits to the community. In China, however, the current participatory mechanism at the project level exists only as part of the environmental impact assessment (EIA) process. With an increasing demand for PIC projects and social equality in China, this suggests a need to bring the participatory process into line with international practice. The aim of this paper, therefore, is to identify the weaknesses of EIA-basedpublicparticipation in China and the means by which it may be improved for the whole lifecycle of PIC schemes. To do this, the results of a series of interviews with a diverse group of experts is reported which analyse the nature and extent of existing problems of publicparticipation in EIA and suggestions for improvement. These indicate that the current level of participation in PIC projects is quite limited, particularly in the crucial earlier stages, primarily due to traditional culture and values, uneven progress in the adoption of participatory mechanisms, the risk of not meeting targets and lack of confidence in public competence. Finally, aprocess flowchart is proposed to guide construction practitioners and the community in general.

Time-dependent rates of molecular evolution

For over half a century, it has been known that the rate of morphological evolution appears to vary with the time frame of measurement. Rates of microevolutionary change, measured between successive generations, were found to be far higher than rates of macroevolutionary change inferred from the fossil record. More recently, it has been suggested that rates of molecular evolution are also time dependent, with the estimated rate depending on the timescale of measurement. This followed surprising observations that estimates of mutation rates, obtained in studies of pedigrees and laboratory mutation-accumulation lines, exceeded long-term substitution rates by an order of magnitude or more. Although a range of studies have provided evidence for such a pattern, the hypothesis remains relatively contentious. Furthermore, there is ongoing discussion about the factors that can cause molecular rate estimates to be dependent on time. Here we present an overview of our current understanding of time-dependent rates. We provide a summary of the evidence for time-dependent rates in animals, bacteria and viruses. We review the various biological and methodological factors that can cause rates to be time dependent, including the effects of natural selection, calibration errors, model misspecification and other artefacts. We also describe the challenges in calibrating estimates of molecular rates, particularly on the intermediate timescales that are critical for an accurate characterization of time-dependent rates. This has important consequences for the use of molecular-clock methods to estimate timescales of recent evolutionary events.