The role of the multiple banded antigen of ureaplasma parvum in intra-amniotic infection : major virulence factor or decoy?

The multiple banded antigen (MBA) is a predicted virulence factor of Ureaplasma species. Antigenic variation of the MBA is a potential mechanism by which ureaplasmas avoid immune recognition and cause chronic infections of the upper genital tract of pregnant women. We tested whether the MBA is involved in the pathogenesis of intra-amniotic infection and chorioamnionitis by injecting virulent or avirulent-derived ureaplasma clones (expressing single MBA variants) into the amniotic fluid of pregnant sheep. At 55 days of gestation pregnant ewes (n = 20) received intra-amniotic injections of virulent-derived or avirulent-derived U. parvum serovar 6 strains (2×104 CFU), or 10B medium (n = 5). Amniotic fluid was collected every two weeks post-infection and fetal tissues were collected at the time of surgical delivery of the fetus (140 days of gestation). Whilst chronic colonisation was established in the amniotic fluid of animals infected with avirulent-derived and virulent-derived ureaplasmas, the severity of chorioamnionitis and fetal inflammation was not different between these groups (p>0.05). MBA size variants (32–170 kDa) were generated in vivo in amniotic fluid samples from both the avirulent and virulent groups, whereas in vitro antibody selection experiments led to the emergence of MBA-negative escape variants in both strains. Anti-ureaplasma IgG antibodies were detected in the maternal serum of animals from the avirulent (40%) and virulent (55%) groups, and these antibodies correlated with increased IL-1β, IL-6 and IL-8 expression in chorioamnion tissue (p<0.05). We demonstrate that ureaplasmas are capable of MBA phase variation in vitro; however, ureaplasmas undergo MBA size variation in vivo, to potentially prevent eradication by the immune response. Size variation of the MBA did not correlate with the severity of chorioamnionitis. Nonetheless, the correlation between a maternal humoral response and the expression of chorioamnion cytokines is a novel finding. This host response may be important in the pathogenesis of inflammation-mediated adverse pregnancy outcomes.

Childbirth and the development of acute trauma symptoms : incidence and contributing factors

Background: Little is known about the relationship between women's birthing experiences and the development of trauma symptoms. This study aimed to determine the incidence of acute trauma symptoms and posttraumatic stress disorder in women as a result of their labor and birth experiences, and to identify factors that contributed to the women's psychological distress. Method: Using a prospective, longitudinal design, women in their last trimester of pregnancy were recruited from four public hospital antenatal clinics. Telephone interviews with 499 participants were conducted at 4 to 6 weeks postpartum to explore the medical and midwifery management of the birth, perceptions of intrapartum care, and the presence of trauma symptoms. Results: One in three women (33%) identified a traumatic birthing event and reported the presence of at least three trauma symptoms. Twenty-eight women (5.6%) met DSM-IV criteria for acute posttraumatic stress disorder. Antenatal variables did not contribute to the development of acute or chronic trauma symptoms. The level of obstetric intervention experienced during childbirth (β= 0.351, p < 0.0001)and the perception of inadequate intrapartum care (β= 0.319, p < 0.0001) during labor were consistently associated with the development of acute trauma symptoms. Conclusions: Posttraumatic stress disorder after childbirth is a poorly recognized phenomenon. Women who experienced both a high level of obstetric intervention and dissatisfaction with their intrapartum care were more likely to develop trauma symptoms than women who received a high level of obstetric intervention or women who perceived their care to be inadequate. These findings should prompt a serious review of intrusive obstetric intervention during labor and delivery, and the care provided to birthing women.

Handling incomplete data in survival analysis with multiple covariates

This paper studies the missing covariate problem which is often encountered in survival analysis. Three covariate imputation methods are employed in the study, and the effectiveness of each method is evaluated within the hazard prediction framework. Data from a typical engineering asset is used in the case study. Covariate values in some time steps are deliberately discarded to generate an incomplete covariate set. It is found that although the mean imputation method is simpler than others for solving missing covariate problems, the results calculated by it can differ largely from the real values of the missing covariates. This study also shows that in general, results obtained from the regression method are more accurate than those of the mean imputation method but at the cost of a higher computational expensive. Gaussian Mixture Model (GMM) method is found to be the most effective method within these three in terms of both computation efficiency and predication accuracy.

Exploring the contested role of mandatory reporting laws in the identification of severe child abuse and neglect

Significant numbers of children are severely abused and neglected by parents and caregivers. Infants and very young children are the most vulnerable and are unable to seek help. To identify these situations and enable child protection and the provision of appropriate assistance, many jurisdictions have enacted ‘mandatory reporting laws’ requiring designated professionals such as doctors, nurses, police and teachers to report suspected cases of severe child abuse and neglect. Other jurisdictions have not adopted this legislative approach, at least partly motivated by a concern that the laws produce dramatic increases in unwarranted reports, which, it is argued, lead to investigations which infringe on people’s privacy, cause trauma to innocent parents and families, and divert scarce government resources from deserving cases. The primary purpose of this paper is to explore the extent to which opposition to mandatory reporting laws is valid based on the claim that the laws produce ‘overreporting’. The first part of this paper revisits the original mandatory reporting laws, discusses their development into various current forms, explains their relationship with policy and common law reporting obligations, and situates them in the context of their place in modern child protection systems. This part of the paper shows that in general, contemporary reporting laws have expanded far beyond their original conceptualisation, but that there is also now a deeper understanding of the nature, incidence, timing and effects of different types of severe maltreatment, an awareness that the real incidence of maltreatment is far higher than that officially recorded, and that there is strong evidence showing the majority of identified cases of severe maltreatment are the result of reports by mandated reporters. The second part of this paper discusses the apparent effect of mandatory reporting laws on ‘overreporting’ by referring to Australian government data about reporting patterns and outcomes, with a particular focus on New South Wales. It will be seen that raw descriptive data about report numbers and outcomes appear to show that reporting laws produce both desirable consequences (identification of severe cases) and problematic consequences (increased numbers of unsubstantiated reports). Yet, to explore the extent to which the data supports the overreporting claim, and because numbers of unsubstantiated reports alone cannot demonstrate overreporting, this part of the paper asks further questions of the data. Who makes reports, about which maltreatment types, and what are the outcomes of those reports? What is the nature of these reports; for example, to what extent are multiple numbers of reports made about the same child? What meaning can be attached to an ‘unsubstantiated’ report, and can such reports be used to show flaws in reporting effectiveness and problems in reporting laws? It will be suggested that available evidence from Australia is not sufficiently detailed or strong to demonstrate the overreporting claim. However, it is also apparent that, whether adopting an approach based on public health and or other principles, much better evidence about reporting needs to be collected and analyzed. As well, more nuanced research needs to be conducted to identify what can reasonably be said to constitute ‘overreports’, and efforts must be made to minimize unsatisfactory reporting practice, informed by the relevant jurisdiction’s context and aims. It is also concluded that, depending on the jurisdiction, the available data may provide useful indicators of positive, negative and unanticipated effects of specific components of the laws, and of the strengths, weaknesses and needs of the child protection system.

Information sharing in Onesocialweb using a multiple profile manager to better informed medical decision making processes

The study shows an alternative solution to existing efforts at solving the problem of how to centrally manage and synchronise users’ Multiple Profiles (MP) across multiple discrete social networks. Most social network users hold more than one social network account and utilise them in different ways depending on the digital context (Iannella, 2009a). They may, for example, enjoy friendly chat on Facebook1, professional discussion on LinkedIn2, and health information exchange on PatientsLikeMe3 In this thesis the researcher proposes a framework for the management of a user’s multiple online social network profiles. A demonstrator, called Multiple Profile Manager (MPM), will be showcased to illustrate how effective the framework will be. The MPM will achieve the required profile management and synchronisation using a free, open, decentralized social networking platform (OSW) that was proposed by the Vodafone Group in 2010. The proposed MPM will enable a user to create and manage an integrated profile (IP) and share/synchronise this profile with all their social networks. The necessary protocols to support the prototype are also proposed by the researcher. The MPM protocol specification defines an Extensible Messaging and Presence Protocol (XMPP) extension for sharing vCard and social network accounts information between the MPM Server, MPM Client, and social network sites (SNSs). . Therefore many web users need to manage disparate profiles across many distributed online sources. Maintaining these profiles is cumbersome, time-consuming, inefficient, and may lead to lost opportunity. The writer of this thesis adopted a research approach and a number of use cases for the implementation of the project. The use cases were created to capture the functional requirements of the MPM and to describe the interactions between users and the MPM. In the research a development process was followed in establishing the prototype and related protocols. The use cases were subsequently used to illustrate the prototype via the screenshots taken of the MPM client interfaces. The use cases also played a role in evaluating the outcomes of the research such as the framework, prototype, and the related protocols. An innovative application of this project is in the area of public health informatics. The researcher utilised the prototype to examine how the framework might benefit patients and physicians. The framework can greatly enhance health information management for patients and more importantly offer a more comprehensive personal health overview of patients to physicians. This will give a more complete picture of the patient’s background than is currently available and will prove helpful in providing the right treatment. The MPM prototype and related protocols have a high application value as they can be integrated into the real OSW platform and so serve users in the modern digital world. They also provide online users with a real platform for centrally storing their complete profile data, efficiently managing their personal information, and moreover, synchronising the overall complete profile with each of their discrete profiles stored in their different social network sites.

Challenges in the context-aware management of business processes : a multiple case study

Current conceptualizations of organizational processes consider them as internally optimized yet static systems. Still, turbulences in the contextual environment of a firm often lead to adaptation requirements that these processes are unable to fulfil. Based on a multiple case study of the core processes of two large organizations, we offer an extended conceptualisation of business processes as complex adaptive systems. This conceptualization can enable firms to optimise business processes by analysing operations in different contexts and by examining the complex interaction between external, contextual elements and internal agent schemata. From this analysis, we discuss how information technology can play a vital goal in achieving this goal by providing discovery, analysis, and automation support. We detail implications for research and practice.

The FAM deubiquitylating enzyme localizes to multiple points of protein trafficking in epithelia, where it associates with E-cadherin and β-catenin

Ubiquitylation is a necessary step in the endocytosis and lysosomal trafficking of many plasma membrane proteins and can also influence protein trafficking in the biosynthetic pathway. Although a molecular understanding of ubiquitylation in these processes is beginning to emerge, very little is known about the role deubiquitylation may play. Fat Facets in mouse (FAM) is substrate-specific deubiquitylating enzyme highly expressed in epithelia where it interacts with its substrate, β-catenin. Here we show, in the polarized intestinal epithelial cell line T84, FAM localized to multiple points of protein trafficking. FAM interacted with β-catenin and E-cadherin in T84 cells but only in subconfluent cultures. FAM extensively colocalized with β-catenin in cytoplasmic puncta but not at sites of cell-cell contact as well as immunoprecipitating with β-catenin and E-cadherin from a higher molecular weight complex (~500 kDa). At confluence FAM neither colocalized with, nor immunoprecipitated, β-catenin or E-cadherin, which were predominantly in a larger molecular weight complex (~2 MDa) at the cell surface. Overexpression of FAM in MCF-7 epithelial cells resulted in increased β-catenin levels, which localized to the plasma membrane. Expression of E-cadherin in L-cell fibroblasts resulted in the relocalization of FAM from the Golgi to cytoplasmic puncta. These data strongly suggest that FAM associates with E-cadherin and β-catenin during trafficking to the plasma membrane.

A Bias in ML Estimates of Branch Lengths in the Presence of Multiple Signals

Sequence data often have competing signals that are detected by network programs or Lento plots. Such data can be formed by generating sequences on more than one tree, and combining the results, a mixture model. We report that with such mixture models, the estimates of edge (branch) lengths from maximum likelihood (ML) methods that assume a single tree are biased. Based on the observed number of competing signals in real data, such a bias of ML is expected to occur frequently. Because network methods can recover competing signals more accurately, there is a need for ML methods allowing a network. A fundamental problem is that mixture models can have more parameters than can be recovered from the data, so that some mixtures are not, in principle, identifiable. We recommend that network programs be incorporated into best practice analysis, along with ML and Bayesian trees.

UHT milk contains multiple forms of αS1-casein that undergo degradative changes during storage

Milk proteins are susceptible to chemical changes during processing and storage. We used proteomic tools to analyse bovine αS1-casein in UHT milk. 2-D gels of freshly processed milk αS1-casein was presented as five or more spots due to genetic polymorphism and variable phosphorylation. MS analysis after phosphopeptide enrichment allowed discrimination between phosphorylation states and genetic variants. We identified a new alternatively-spliced isoform with a deletion of exon 17, producing a new C-terminal sequence, K164SQVNSEGLHSYGL177, with a novel phosphorylation site at S174. Storage of UHT milk at elevated temperatures produced additional, more acidic αS1-casein spots on the gels and decreased the resolution of minor forms. MS analysis indicated that non-enzymatic deamidation and loss of the N-terminal dipeptide were the major contributors to the changing spot pattern. These results highlight the important role of storage temperature in the stability of milk proteins and the utility of proteomic techniques for analysis of proteins in food.

Multiple distribution static synchronous compensators for distribution feeder voltage support

The potential of multiple distribution static synchronous compensators (DSTATCOMs) to improve the voltage profile of radial distribution networks has been reported in the literature by few authors. However, the operation of multiple DSTATCOMs across a distribution feeder may introduce control interactions and/or voltage instability. This study proposes a control scheme that alleviates interactions among controllers and enhances proper reactive power sharing among DSTATCOMs. A generalised mathematical model is presented to analyse the interactions among any number of DSTATCOMs in the network. The criterion for controller design is developed by conducting eigenvalue analysis on this mathematical model. The proposed control scheme is tested in time domain on a sample radial distribution feeder installed with multiple DSTATCOMs and test results are presented.