Modulation of LPS-induced chorioamnionitis by ureaplasma parvum in sheep chorioamnionitis in sheep

ABSTRACT Objective: Ureaplasma parvum colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that ureaplasma colonization of amniotic fluid will modulate chorioamnionitis induced by E.coli lipopolysaccharide (LPS). Methods: Sheep received intra-amniotic (IA) injections of media (control) or live ureaplasma either 7 or 70d before delivery. Another group received IA LPS 2d before delivery. To test for interactions, U.parvum exposed animals were challenged with IA LPS, and delivered 2d later. All animals were delivered preterm at 125±1 day gestation. Results: Both IA ureaplasmas and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of pro-inflammatory cytokines and myeloperoxidase in leukocytes, while ureaplasmas alone caused modest responses. Interestingly, 7d but not 70d ureaplasma exposure significantly downregulated LPS induced pro-inflammatory cytokines and myeloperoxidase expression in the chorioamnion. Conclusion: U.parvum can suppress LPS induced experimental chorioamnionitis.

Ureaplasma parvum multiple banded antigen (MBA) size variation - association with fetal inflammation in a sheep model (Published abstract)

Background: Ureaplasma species are the most prevalent isolates from women who deliver preterm. The MBA, a surface exposed lipoprotein, is a key virulence factor of ureaplasmas. We investigated MBA variation after chronic and acute intra-amniotic (IA) ureaplasma infections. Method: U. parvum serovar 3 (2x104 colony-forming-units) was injected IA into pregnant ewes at: 55 days gestation (d, term = 145d) (n=8); 117d (n=8) and 121d (n=8). Fetuses were delivered surgically (124d) and ureaplasmas cultured from amniotic fluid (AF), chorioamnion, fetal lung (FL) and umbilical cord were tested by western blot and PCR assays to demonstrate MBA and mba gene variation respectively. Tissue sections were sectioned and stained by haemotoxylin and eosin and inflammatory cell counts and pathology were reported (blinded to outcome). Results: Numerous MBA/mba variants were generated in vivo after chronic exposure to ureaplasma infection but after acute infection no variants (3d) or very few variants (7d) were generated. Identical MBA variants were detected within the AF and FL but different ureaplasma variants were detected within chorioamnion specimens. The severity of inflammation within chronically infected tissues varied between animals ranging from no inflammation to severe inflammation with/without fibrosis. Chorioamnion, FL and cord from the same animal demonstrated the same degree of inflammation. Conclusions: MBA/mba variation in vivo occurred after the initiation of the host immune response and we propose that ureaplasmas vary the MBA antigen to evade the host immune response. In some animals there was no inflammation despite colonisation with high numbers of ureaplasmas.

Mid-gestation intra-amniotic infection with Ureaplasma parvum is resolved within spiny mice (Acomys cahirinus) by term delivery: but caused chronic infection of fetal lungs and placentae

Background: Ureaplasma species in amniotic fluid at the time of second-trimester amniocentesis increases the risk of preterm birth, but most affected pregnancies continue to term (Gerber et al. J Infect Dis 2003). We aimed to model intra-amniotic (IA) ureaplasma infection in spiny mice, a species with a relatively long gestation (39 days) that allows investigation of the disposition and possible clearance of ureaplasmas in the feto-placental compartment. Method: Pregnant spiny mice received IA injections of U. parvum serovar 6 (10µL, 1x104 colony-forming-units in PBS) or 10B media (10µL; control) at 20 days (d) of gestation (term=39d). At 37d fetuses (n=3 ureaplasma, n=4 control) were surgically delivered and tissues were collected for; bacterial culture, ureaplasma mba and urease gene expression by PCR, tissue WBC counts and indirect fluorescent antibody (IFA) staining using anti-ureaplasma serovar 6 (rabbit) antiserum. Maternal and fetal plasma IgG was measured by Western blot. Results: Ureaplasmas were not detected by culture or PCR in fetal or maternal tissues but were visualized by IFA within placental and fetal lung tissues, in association with inflammatory changes and elevated WBC counts (p<0.0001). Anti-ureaplasma IgG was detected in maternal (2/2 tested) and fetal (1/2 tested) plasma but not in controls (0/3). Conclusions: IA injection of ureaplasmas in mid-gestation spiny mice caused persistent fetal lung and placental infection even though ureaplasmas were undetectable using standard culture or PCR techniques. This is consistent with resolution of IA infection, which may occur in human pregnancies that continue to term despite detection of ureaplasmas in mid-gestation.

Final-state effects in neutron Compton scattering measurements on zirconium deuteride and beryllium

We report inelastic neutron scattering measurements of the neutron Compton profile, J(y), for Be and for D in polycrystalline ZrD2 over a range of momentum transfers, q between 27 and 178 °A−1. The measurements were performed using the inverse geometry spectrometer eVS which is situated at the UK pulsed spallation neutron source ISIS. We have investigated deviations from impulse approximation (IA) scattering which are generically referred to as final state effects (FSEs) using a method described by Sears. This method allows both the magnitude and the q dependence of the FSE to be studied. Analysis of the measured data was compared with analysis of numerical simulations based on the harmonic approximation and good agreement was found for both ZrD2 and Be. Finally we have shown how (∇2V), where V is the interatomic potential, can be extracted from the antisymmetric component of J(y).

Accountable-eHealth systems : the next step forward for privacy

eHealth systems promise enviable benefits and capabilities for healthcare delivery. However, the technologies that make these capabilities possible introduce undesirable drawbacks such as information security related threats, which need to be appropriately addressed. Lurking in these threats are information privacy concerns. Addressing them has proven to be difficult because they often conflict with information access requirements of healthcare providers. Therefore, it is important to achieve an appropriate balance between these requirements. We contend that information accountability (IA) can achieve this balance. In this paper, we introduce accountable-eHealth (AeH) systems, which are eHealth systems that utilise IA as a measure of information privacy. We discuss how AeH system protocols can successfully achieve the aforementioned balance of requirements. As a means of implementation feasibility, we compare characteristics of AeH systems with Australia’s Personally Controlled Electronic Health Record (PCEHR) sys-tem and identify similarities and highlight the differences and the impact those differences would have to the eHealth domain.

Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: A verification study

Background: A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival. Methods: Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells × staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated. Results: 101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p= 0.024) and mTOR staining (p= 0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p= 0.037 and p= 0.020, respectively). Conclusions: Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway. © 2011 Elsevier Ireland Ltd.

Is intent-aware expected reciprocal rank sufficient to evaluate diversity?

In this paper we define two models of users that require diversity in search results; these models are theoretically grounded in the notion of intrinsic and extrinsic diversity. We then examine Intent-Aware Expected Reciprocal Rank (ERR-IA), one of the official measures used to assess diversity in TREC 2011-12, with respect to the proposed user models. By analyzing ranking preferences as expressed by the user models and those estimated by ERR-IA, we investigate whether ERR-IA assesses document rankings according to the requirements of the diversity retrieval task expressed by the two models. Empirical results demonstrate that ERR-IA neglects query-intents coverage by attributing excessive importance to redundant relevant documents. ERR-IA behavior is contrary to the user models that require measures to first assess diversity through the coverage of intents, and then assess the redundancy of relevant intents. Furthermore, diversity should be considered separately from document relevance and the documents positions in the ranking.

Designing and implementing usable and useful Accountable-eHealth systems

This tutorial primarily focuses on the technical challenges surrounding the design and implementation of Accountable-eHealth (AeH) systems. The potential benefits of shared eHealth records systems are promising for the future of improved healthcare; however, their uptake is hindered by concerns over the privacy and security of patient information. In the current eHealth environment, there are competing requirements between healthcare consumers' (i.e. patients) requirements and healthcare professionals' requirements. While consumers want control over their information, healthcare professionals want access to as much information as required in order to make well informed decisions. This conflict is evident in the review of Australia's PCEHR system. Accountable-eHealth systems aim to balance these concerns by implementing Information Accountability (IA) mechanisms. AeH systems create an eHealth environment where health information is available to the right person at the right time without rigid barriers whilst empowering the consumers with information control and transparency, thus, enabling the creation of shared eHealth records that can be useful to both patients and HCPs. In this half-day tutorial, we will discuss and describe the technical challenges surrounding the implementation of AeH systems and the solutions we have devised. A prototype AeH system will be used to demonstrate the functionality of AeH systems, and illustrate some of the proposed solutions. The topics that will be covered include: designing for usability in AeH systems, the privacy and security of audit mechanisms, providing for diversity of users, the scalability of AeH systems, and finally the challenges of enabling research and Big Data Analytics on shared eHealth Records while ensuring accountability and privacy are maintained.

The role of the yeast cleavage and polyadenylation factor subunit Ydh1p/Cft2p in pre-mRNA 3'-end formation

Cleavage and polyadenylation factor (CPF) is a multi‐protein complex that functions in pre‐mRNA 3′‐end formation and in the RNA polymerase II (RNAP II) transcription cycle. Ydh1p/Cft2p is an essential component of CPF but its precise role in 3′‐end processing remained unclear. We found that mutations in YDH1 inhibited both the cleavage and the polyadenylation steps of the 3′‐end formation reaction in vitro. Recently, we demonstrated that an important function of CPF lies in the recognition of poly(A) site sequences and RNA binding analyses suggesting that Ydh1p/Cft2p interacts with the poly(A) site region. Here we show that mutant ydh1 strains are deficient in the recognition of the ACT1 cleavage site in vivo. The C‐terminal domain (CTD) of RNAP II plays a major role in coupling 3′‐end processing and transcription. We provide evidence that Ydh1p/Cft2p interacts with the CTD of RNAP II, several other subunits of CPF and with Pcf11p, a component of CF IA. We propose that Ydh1p/Cft2p contributes to the formation of important interaction surfaces that mediate the dynamic association of CPF with RNAP II, the recognition of poly(A) site sequences and the assembly of the polyadenylation machinery on the RNA substrate.

Independent functions of yeast Pcf11p in pre-mRNA 3' end processing and in transcription termination

Pcf11p, an essential subunit of the yeast cleavage factor IA, is required for pre‐mRNA 3′ end processing, binds to the C‐terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAP II) and is involved in transcription termination. We show that the conserved CTD interaction domain (CID) of Pcf11p is essential for cell viability. Interestingly, the CTD binding and 3′ end processing activities of Pcf11p can be functionally uncoupled from each other and provided by distinct Pcf11p fragments in trans. Impaired CTD binding did not affect the 3′ end processing activity of Pcf11p and a deficiency of Pcf11p in 3′ end processing did not prevent CTD binding. Transcriptional run‐on analysis with the CYC1 gene revealed that loss of cleavage activity did not correlate with a defect in transcription termination, whereas loss of CTD binding did. We conclude that Pcf11p is a bifunctional protein and that transcript cleavage is not an obligatory step prior to RNAP II termination.

Implementing a new genre of eHealth system in a reticent environment

This tutorial primarily focuses on the social aspects of implementing a novel eHealth systems called Accountable-eHealth (AeH) systems. The main focus of AeH systems is mitigating information privacy concerns whilst facilitating appropriate access to information for users, and is based on the principles of information accountability (IA).

Generation and assessment of accuracy of Digital Elevation Model by using Pcigeomatica (10.3)

This study aims to assess the accuracy of Digital Elevation Model (DEM) which is generated by using Toutin’s model. Thus, Toutin’s model was run by using OrthoEngineSE of PCI Geomatics 10.3.Thealong-track stereoimages of Advanced Spaceborne Thermal Emission and Reflection radiometer (ASTER) sensor with 15 m resolution were used to produce DEM on an area with low and near Mean Sea Level (MSL) elevation in Johor Malaysia. Despite the satisfactory pre-processing results the visual assessment of the DEM generated from Toutin’s model showed that the DEM contained many outliers and incorrect values. The failure of Toutin’s model may mostly be due to the inaccuracy and insufficiency of ASTER ephemeris data for low terrains as well as huge water body in the stereo images.

Petrology and textural classification of the Jericho kimberlite, northern Slave Province, Nunavut, Canada

The paper presents data on petrology, bulk rock and mineral compositions, and textural classification of the Middle Jurassic Jericho kimberlite (Slave craton, Canada). The kimberlite was emplaced as three steep-sided pipes in granite that was overlain by limestones and minor soft sediments. The pipes are infilled with hypabyssal and pyroclastic kimberlites and connected to a satellite pipe by a dyke. The Jericho kimberlite is classified as a Group Ia, lacking groundmass tetraferriphlogopite and containing monticellite pseudomorphs. The kimberlite formed, during several consecutive emplacement events of compositionally different batches of kimberlite magma. Core-logging and thin-section observations identified at least two phases of hypabyssal kimberlites and three phases of pyroclastic kimberlites. Hypabyssal kimberlites intruded as a main dyke (HK1) and as late small-volume aphanitic and vesicular dykes. Massive pyroclastic kimberlite (MPK1) predominantly filled the northern and southern lobes of the pipe and formed from magma different from the HK1 magma. The MPK1 magma crystallized Ti-, Fe-, and Cr-rich phlogopite without rims of barian phlogopite, and clinopyroxene and spinel without atoll structures. MPK1 textures, superficially reminiscent of tuffisitic kimberlite, are caused by pervasive contamination by granite xenoliths. The next explosive events filled the central lobe with two varieties of pyroclastic kimberlite: (1) massive and (2) weakly bedded, normally graded pyroclastic kimberlite. The geology of the Jericho pipe differs from the geology of South African or the Prairie kimberlites, but may resemble Lac de Gras pipes, in which deeper erosion removed upper fades of resedimented kimberlites.

Does Social Anxiety and Bullying Victimization Create Loneliness in Young People?

Loneliness is a distressing, complex, universal phenomena. This chapter focuses on loneliness in children and adolescents, specifically examining research on the relationship between young people’s social anxiety and loneliness and the role of bullying victimisation and loneliness. It answers the question does social anxiety and bullying victimization create loneliness in young people. It was found from a review of the literature that all three concepts are distinct yet inextricably intertwined as antecedents and consequences of each other. The constructs are bi-directional, often forming a feedback loop or negative cycle. In addition these variables can also be mediating and moderating variables. Implications for interventions are discussed.

The design and implementation of an Information Accountability Framework for eHealth systems

This tutorial primarily focuses on the implementation of Information Accountability (IA) protocols defined in an Information Accountability Framework (IAF) in eHealth systems. Concerns over the security and privacy of patient information are one of the biggest hindrances to sharing health information and the wide adoption of eHealth systems. At present, there are competing requirements between healthcare consumers' (i.e. patients) requirements and healthcare professionals' (HCP) requirements. While consumers want control over their information, healthcare professionals want access to as much information as required in order to make well-informed decisions and provide quality care. This conflict is evident in the review of Australia's PCEHR system and in recent studies of patient control of access to their eHealth information. In order to balance these requirements, the use of an Information Accountability Framework devised for eHealth systems has been proposed. Through the use of IA protocols, so-called Accountable-eHealth systems (AeH) create an eHealth environment where health information is available to the right person at the right time without rigid barriers whilst empowering the consumers with information control and transparency. In this half-day tutorial, we will discuss and describe the technical challenges surrounding the implementation of the IAF protocols into existing eHealth systems and demonstrate their use. The functionality of the protocols and AeH systems will be demonstrated, and an example of the implementation of the IAF protocols into an existing eHealth system will be presented and discussed.