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.

Temperature dependent electrical resistivity in expoxy : multiwall carbon nanotube nanocomposites

Thin films of expoxy nanocomposites modified by multiwall carbon nanotubes (MWCNTs) were prepared by shear mixing and spin casting. The electrical behaviour and its dependence with temperature between 243 and 353 degrees Kelvin were characterized by measuring the direct current (DC) conductivity. Depending on the fabrication process, both linear and non-linear relationships between conductivity and temperature were observed. In addition, the thermal history also played a role in dictating the conductivity. The implications of these observations for potential application of these files as strain sensors are discussed.

The internetalisation of information, knowledge and interaction components of the firm’s internationalisation process

Transcending traditional national borders, the Internet is an evolving technology that has opened up many new international market opportunities. However, ambiguity remains, with limited research and understanding of how the Internet influences the firm’s internationalisation process components. As a consequence, there has been a call for further investigation of the phenomenon. Thus, the purpose of this study was to investigate the Internet’s impact on the internationalisation process components, specifically, information availability, information usage, interactive communication and international market growth. Analysis was undertaken using structural equation modelling. Findings highlight the mediating impact of the Internet on information and knowledge transference in the internationalisation process. Contributions of the study test conceptualisations and give statistical validation of interrelationships, while illuminating the Internet’s impact on firm internationalisation.

A Bayesian‐Markov process for reliability prediction

Accurate reliability prediction for large-scale, long lived engineering is a crucial foundation for effective asset risk management and optimal maintenance decision making. However, a lack of failure data for assets that fail infrequently, and changing operational conditions over long periods of time, make accurate reliability prediction for such assets very challenging. To address this issue, we present a Bayesian-Marko best approach to reliability prediction using prior knowledge and condition monitoring data. In this approach, the Bayesian theory is used to incorporate prior information about failure probabilities and current information about asset health to make statistical inferences, while Markov chains are used to update and predict the health of assets based on condition monitoring data. The prior information can be supplied by domain experts, extracted from previous comparable cases or derived from basic engineering principles. Our approach differs from existing hybrid Bayesian models which are normally used to update the parameter estimation of a given distribution such as the Weibull-Bayesian distribution or the transition probabilities of a Markov chain. Instead, our new approach can be used to update predictions of failure probabilities when failure data are sparse or nonexistent, as is often the case for large-scale long-lived engineering assets.

Fast detection of exact clones in business process model repositories

As organizations reach higher levels of business process management maturity, they often find themselves maintaining very large process model repositories, representing valuable knowledge about their operations. A common practice within these repositories is to create new process models, or extend existing ones, by copying and merging fragments from other models. We contend that if these duplicate fragments, a.k.a. ex- act clones, can be identified and factored out as shared subprocesses, the repository’s maintainability can be greatly improved. With this purpose in mind, we propose an indexing structure to support fast detection of clones in process model repositories. Moreover, we show how this index can be used to efficiently query a process model repository for fragments. This index, called RPSDAG, is based on a novel combination of a method for process model decomposition (namely the Refined Process Structure Tree), with established graph canonization and string matching techniques. We evaluated the RPSDAG with large process model repositories from industrial practice. The experiments show that a significant number of non-trivial clones can be efficiently found in such repositories, and that fragment queries can be handled efficiently.

Approximate clone detection in repositories of business process models

Evidence exists that repositories of business process models used in industrial practice contain significant amounts of duplication. This duplication may stem from the fact that the repository describes variants of the same pro- cesses and/or because of copy/pasting activity throughout the lifetime of the repository. Previous work has put forward techniques for identifying duplicate fragments (clones) that can be refactored into shared subprocesses. However, these techniques are limited to finding exact clones. This paper analyzes the prob- lem of approximate clone detection and puts forward two techniques for detecting clusters of approximate clones. Experiments show that the proposed techniques are able to accurately retrieve clusters of approximate clones that originate from copy/pasting followed by independent modifications to the copied fragments.

Factors of process model comprehension : findings from a series of experiments

In order to make good decisions about the design of information systems, an essential skill is to understand process models of the business domain the system is intended to support. Yet, little knowledge to date has been established about the factors that affect how model users comprehend the content of process models. In this study, we use theories of semiotics and cognitive load to theorize how model and personal factors influence how model viewers comprehend the syntactical information of process models. We then report on a four-part series of experiments, in which we examined these factors. Our results show that additional semantical information impedes syntax comprehension, and that theoretical knowledge eases syntax comprehension. Modeling experience further contributes positively to comprehension efficiency, measured as the ratio of correct answers to the time taken to provide answers. We discuss implications for practice and research.

Does venture opportunity variation matter? Investigating systemic process differences between innovative and imitative new ventures

The central thesis in the article is that the venture creation process is different for innovative versus imitative ventures. This holds up; the pace of the process differs by type of venture as do, in line with theory-based hypotheses, the effects of certain human capital (HC) and social capital (SC) predictors. Importantly, and somewhat unexpectedly, the theoretically derived models using HC, SC, and certain controls are relatively successful explaining progress in the creation process for the minority of innovative ventures, but achieve very limited success for the imitative majority. This may be due to a rationalistic bias in conventional theorizing and suggests that there is need for considerable theoretical development regarding the important phenomenon of new venture creation processes. Another important result is that the building up of instrumental social capital, which we assess comprehensively and as a time variant construct, is important for making progress with both types of ventures, and increasingly, so as the process progresses. This result corroborates with stronger operationalization and more appropriate analysis method what previously published research has only been able to hint at.

A software framework for risk-aware business process management

With the large diffusion of Business Process Managemen (BPM) automation suites, the possibility of managing process-related risks arises. This paper introduces an innovative framework for process-related risk management and describes a working implementation realized by extending the YAWL system. The framework covers three aspects of risk management: risk monitoring, risk prevention, and risk mitigation. Risk monitoring functionality is provided using a sensor-based architecture, where sensors are defined at design time and used at run-time for monitoring purposes. Risk prevention functionality is provided in the form of suggestions about what should be executed, by who, and how, through the use of decision trees. Finally, risk mitigation functionality is provided as a sequence of remedial actions (e.g. reallocating, skipping, rolling back of a work item) that should be executed to restore the process to a normal situation.

Online retailing versus traditional stores in the purchasing decision making process

Due to proliferation of online stores prior expectations that retailing would move completely online were not fulfilled. Previous research about consumers’ preference of retailing channels suggested that online sales are driven by the convenience of online shopping, or as a natural extension of online searches. This paradigm has changed over the years. Changes in consumer behaviour are indicating that while consumers are searching online using various information sources to learn about products, ultimately when purchasing, consumers are shifting between online and offline retailing channels depending on various factors. Online shopping is still considered to be a convenient way to purchase goods, but the convenience is not the key factor. This qualitative research is based on 22 in-depth interviews with shoppers in Australia.

How Does Information Processing Speed Relate to the Attentional Blink?

Background When observers are asked to identify two targets in rapid sequence, they often suffer profound performance deficits for the second target, even when the spatial location of the targets is known. This attentional blink (AB) is usually attributed to the time required to process a previous target, implying that a link should exist between individual differences in information processing speed and the AB. Methodology/Principal Findings The present work investigated this question by examining the relationship between a rapid automatized naming task typically used to assess information-processing speed and the magnitude of the AB. The results indicated that faster processing actually resulted in a greater AB, but only when targets were presented amongst high similarity distractors. When target-distractor similarity was minimal, processing speed was unrelated to the AB. Conclusions/Significance Our findings indicate that information-processing speed is unrelated to target processing efficiency per se, but rather to individual differences in observers' ability to suppress distractors. This is consistent with evidence that individuals who are able to avoid distraction are more efficient at deploying temporal attention, but argues against a direct link between general processing speed and efficient information selection.

Conflict or consensus : an investigation of stakeholder concerns during the participation process of major infrastructure and construction projects in Hong Kong

Public participate in the planning and design of major public infrastructure and construction (PIC) projects is crucial to their success, as the interests of different stakeholders can be systematically captured and built into the finalised scheme. However, public participation may not always yield a mutually acceptable solution, especially when the interests of stakeholders are diverse and conflicting. Confrontations and disputes can arise unless the concerns or needs of the community are carefully analysed and addressed. The aim of the paper is to propose a systematic method of analysing stakeholder concerns relating to PIC projects by examining the degree of consensus and/or conflict involved. The results of a questionnaire survey and a series of interviews with different entities are provided, which indicate the existence of a significant divergence of views among stakeholder groups and that conflicts arise when there is a mismatch between peoples’ perception concerning money and happiness on the one hand and development and damages on the other. Policy and decision-makers should strive to resolve at least the majority of conflicts that arise throughout the lifecycle of major PIC projects so as to maximise their chance of success.

Interlocked projects in safety competency and safety effectiveness indicators in the construction sector

Safety culture is a concept that has long been accepted in high risk industries such as aviation, nuclear industries and mining, however, considerable research is now also being undertaken within the construction sector. This paper discusses three recent interlocked projects undertaken in the Australian construction industry. The first project examined the development and implementation of a safety competency framework targeted at safety critical positions (SCP's) across first tier construction organisations. Combining qualitative and quantitative methods, the project: developed a matrix of SCP's (n=11) and safety management tasks (SMTs; n=39); mapped the process steps for their acquisition and development; detailed the knowledge, skills and behaviours required for all SMTs; and outlined potential organisational cultural outcomes from a successful implementation of the framework. The second project extended this research to develop behavioural guidelines for leaders to drive safety culture change down to second tier companies and to assist them to customise their own competency framework and implementation guidelines to match their aspirations and resources. The third interlocked project explored the use of safety effectiveness indicators (SEIs) as an industry-relevant assessment tool for reducing risk on construction sites. With direct linkages to safety competencies and SMT's, the SEIs are the next step towards an integrated safety cultural approach to safety and extend the concept of positive performance indicators (PPIs) by providing a valid, reliable, and user friendly measurement platform. Taken together, the results of the interlocked projects suggest that industry engaged collaborative safety culture research has many potential benefits for the construction industry.

Wind-energy based path planning for electric unmanned aerial vehicles using Markov Decision Processes

Exploiting wind-energy is one possible way to ex- tend flight duration for Unmanned Arial Vehicles. Wind-energy can also be used to minimise energy consumption for a planned path. In this paper, we consider uncertain time-varying wind fields and plan a path through them. A Gaussian distribution is used to determine uncertainty in the Time-varying wind fields. We use Markov Decision Process to plan a path based upon the uncertainty of Gaussian distribution. Simulation results that compare the direct line of flight between start and target point and our planned path for energy consumption and time of travel are presented. The result is a robust path using the most visited cell while sampling the Gaussian distribution of the wind field in each cell.

A requirements framework for semantic business process modelling

The emergence of semantic technologies to deal with the underlying meaning of things, instead of a purely syntactical representation, has led to new developments in various fields, including business process modeling. Inspired by artificial intelligence research, technologies for semantic Web services have been proposed and extended to process modeling. However, the applicablility of semantic Web services for semantic business processes is limited because business processes encompass wider requirements of business than Web services. In particular, processes are concerned with the composition of tasks, that is, in which order activities are carried out, regardless of their implementation details; resources assigned to carry out tasks, such as machinery, people, and goods; data exchange; and security and compliance concerns.