Impact of Routine Fractional Flow Reserve Evaluation During Coronary Angiography on Management Strategy and Clinical Outcome: One-Year Results of the POST-IT.

Penetration of fractional flow reserve (FFR) in clinical practice varies extensively, and the applicability of results from randomized trials is understudied. We describe the extent to which the information gained from routine FFR affects patient management strategy and clinical outcome. METHODS AND RESULTS: Nonselected patients undergoing coronary angiography, in which at least 1 lesion was interrogated by FFR, were prospectively enrolled in a multicenter registry. FFR-driven change in management strategy (medical therapy, revascularization, or additional stress imaging) was assessed per-lesion and per-patient, and the agreement between final and initial strategies was recorded. Cardiovascular death, myocardial infarction, or unplanned revascularization (MACE) at 1 year was recorded. A total of 1293 lesions were evaluated in 918 patients (mean FFR, 0.81±0.1). Management plan changed in 406 patients (44.2%) and 584 lesions (45.2%). One-year MACE was 6.9%; patients in whom all lesions were deferred had a lower MACE rate (5.3%) than those with at least 1 lesion revascularized (7.3%) or left untreated despite FFR≤0.80 (13.6%; log-rank P=0.014). At the lesion level, deferral of those with an FFR≤0.80 was associated with a 3.1-fold increase in the hazard of cardiovascular death/myocardial infarction/target lesion revascularization (P=0.012). Independent predictors of target lesion revascularization in the deferred lesions were proximal location of the lesion, B2/C type and FFR. CONCLUSIONS: Routine FFR assessment of coronary lesions safely changes management strategy in almost half of the cases. Also, it accurately identifies patients and lesions with a low likelihood of events, in which revascularization can be safely deferred, as opposed to those at high risk when ischemic lesions are left untreated, thus confirming results from randomized trials.

The modern state and the re-creation of the indigenous other: The case of the authentic Sami in Sweden and the white man's Indian in the United States of America

The present study comparatively examined the socio-political and economic transformation of the indigenous Sámi in Sweden and the Indian American in the United States of America occurring first as a consequence of colonization and later as a product of interaction with the modern territorial and industrial state, from approximately 1500 to 1900. ^ The first colonial encounters of the Europeans with these autochthonous populations ultimately created an imagery of the exotic Other and of the noble savage. Despite these disparaging representations, the cross-cultural settings in which these interactions took place also produced the hybrid communities and syncretic life that allowed levels of cultural accommodation, autonomous space, and indigenous agency to emerge. By the nineteenth century, however, the modern territorial and industrial state rearranges the dynamics and reaches of power across a redefined territorial sovereign space, consequently, remapping belongingness and identity. In this context, the status of indigenous peoples, as in the case of Sámi and of Indian Americans, began to change at par with industrialization and with modernity. At this point in time, indigenous populations became a hindrance to be dealt with the legal re-codification of Indigenousness into a vacuumed limbo of disenfranchisement. It is, thus, the modern territorial and industrial state that re-creates the exotic into an indigenous Other. ^ The present research showed how the initial interaction between indigenous and Europeans changed with the emergence of the modern state, demonstrating that the nineteenth century, with its fundamental impulses of industrialism and modernity, not only excluded and marginalized indigenous populations because they were considered unfit to join modern society, it also re-conceptualized indigenous identity into a constructed authenticity.^

Apples, oranges and fruit salad : a Delphi study of the IMC educational mix

Once, we thought that comparing advertising and public relations was a bit like comparing apples and oranges. But with integration the new flavour, many academics are trying to cut and combine and create a fruit salad that will entice their customers and satisfy their stakeholders. While this has produced some culinary triumphs, it has also produced heartburn in equal quantity. This paper seeks the perfect recipe for integrated marketing communication (IMC) education by asking a Delphi panel of IMC champions questions relating to the place of IMC in the university setting; the teaching, research and curriculum development issues and the future for IMC education. The panel draws a chaotic picture of IMC education and identifies some important obstacles to curriculum development. It also predicts a number of key challenges for the future, including turf wars; the lack of faculty experience and enthusiasm to embrace IMC and the desperate need to grow the IMC brand. But perhaps the greatest challenge is how to create a generalist education in a culture of pecialisation that exists both in the university and in the workplace.

A re-examination of the Ghrelin and Ghrelin receptor genes

The last few years have seen dramatic advances in genomics, including the discovery of a large number of non-coding and antisense transcripts. This has revolutionised our understanding of multifaceted transcript structures found within gene loci and their roles in the regulation of development, neurogenesis and other complex processes. The recent and continuing surge of knowledge has prompted researchers to reassess and further dissect gene loci. The ghrelin gene (GHRL) gives rise to preproghrelin, which in turn produces ghrelin, a 28 amino acid peptide hormone that acts via the ghrelin receptor (growth hormone secretagogue receptor/GHSR 1a). Ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, and cancer development. A truncated receptor splice variant, GHSR 1b, does not bind ghrelin, but dimerises with GHSR 1a, and may act as a dominant negative receptor. The gene products of ghrelin and its receptor are frequently overexpressed in human cancer While it is well known that the ghrelin axis (ghrelin and its receptor) plays a range of important functional roles, little is known about the molecular structure and regulation of the ghrelin gene (GHRL) and ghrelin receptor gene (GHSR). This thesis reports the re-annotation of the ghrelin gene, discovery of alternative 5’ exons and transcription start sites, as well as the description of a number of novel splice variants, including isoforms with a putative signal peptide. We also describe the discovery and characterisation of a ghrelin antisense gene (GHRLOS), and the discovery and expression of a ghrelin receptor (growth hormone secretagogue receptor/GHSR) antisense gene (GHSR-OS). We have identified numerous ghrelin-derived transcripts, including variants with extended 5' untranslated regions and putative secreted obestatin and C-ghrelin transcripts. These transcripts initiate from novel first exons, exon -1, exon 0 and a 5' extended 1, with multiple transcription start sites. We used comparative genomics to identify, and RT-PCR to experimentally verify, that the proximal exon 0 and 5' extended exon 1 are transcribed in the mouse ghrelin gene, which suggests the mouse and human proximal first exon architecture is conserved. We have identified numerous novel antisense transcripts in the ghrelin locus. A candidate non-coding endogenous natural antisense gene (GHRLOS) was cloned and demonstrates very low expression levels in the stomach and high levels in the thymus, testis and brain - all major tissues of non-coding RNA expression. Next, we examined if transcription occurs in the antisense orientation to the ghrelin receptor gene, GHSR. A novel gene (GHSR-OS) on the opposite strand of intron 1 of the GHSR gene was identified and characterised using strand-specific RT-PCR and rapid amplification of cDNA ends (RACE). GHSR-OS is differentially expressed and a candidate non-coding RNA gene. In summary, this study has characterised the ghrelin and ghrelin receptor loci and demonstrated natural antisense transcripts to ghrelin and its receptor. Our preliminary work shows that the ghrelin axis generates a broad and complex transcriptional repertoire. This study provides the basis for detailed functional studies of the the ghrelin and GHSR loci and future studies will be needed to further unravel the function, diagnostic and therapeutic potential of the ghrelin axis.

How to tell the difference between a positive image and a stereotype: reading Priscilla, Queen of the Desert

This paper intervenes in critical discussions about the representation of homosexuality. Rejecting the ‘manifest content’ of films, it turns to cultural history to map those public discourses which close down the ways in which films can be discussed. With relation to The Adventures of Priscilla, Queen of the Desert, it examines discussions of the film in Australian newspapers (both queer and mainstream) and finds that while there is disagreement about the interpretation to be made of the film, the terms within which those interpretations can be made are quite rigid. A matrix based on similarity, difference and value provides a series of positions and a vocabulary (transgression, assimilation, positive images and stereotypes) through which to make sense of this film. The article suggests that this matrix, and the idea that similarity and difference provide a suitable axis for making sense of homosexual identity, are problematic in discussing homosexual representation.

Practice and procedure : an application under r367 of the Uniform Civil Procedure Rules may be of use in obtaining copies of otherwise unavailable documents held by government agencies.

In Bowenbrae Pty Ltd v Flying Fighters Maintenance and Restoration [2010] QDC 347 Reid DCJ made orders requiring the plaintiffs to make application under the Freedom of Information Act 1982 (Cth) (“the FOI Act”) for documents sought by the defendant.

Identity and genetic origins : an ethical exploration of the late discovery of adoptive and donor-insemination offspring status

This thesis is an ethical and empirical exploration of the late discovery of genetic origins in two contexts, adoption and sperm donor-assisted conception. This exploration has two interlinked strands of concern. The first is the identification of ‘late discovery’ as a significant issue of concern, deserving of recognition and acknowledgment. The second concerns the ethical implications of late discovery experiences for the welfare of the child. The apparently simple act of recognition of a phenomenon is a precondition to any analysis and critique of it. This is especially important when the phenomenon arises out of social practices that arouse significant debate in ethical and legal contexts. As the new reproductive technologies and some adoption practices remain highly contested, an ethical exploration of this long neglected experience has the potential to offer new insights and perspectives in a range of contexts. It provides an opportunity to revisit developmental debate on the relative merit or otherwise of biological versus social influences, from the perspective of those who have lived this dichotomy in practise. Their experiences are the human face of the effects arising from decisions taken by others to intentionally separate their biological and social worlds, an action which has then been compounded by family and institutional secrecy from birth. This has been accompanied by a failure to ensure that normative standards and values are upheld for them. Following discovery, these factors can be exacerbated by a lack of recognition and acknowledgement of their concerns by family, friends, community and institutions. Late discovery experiences offer valuable insights to inform discussions on the ethical meanings of child welfare, best interests, parental responsibility, duty of care and child identity rights in this and other contexts. They can strengthen understandings of what factors are necessary for a child to be able to live a reasonably happy or worthwhile life.

Differential expression and distribution of syndecan-1 and -2 in periodontal wound healing of the rat

Cell-surface proteoglycans participate in several biological functions including interactions with adhesion molecules, growth factors and a variety of other effector molecules. Accordingly, these molecules play a central role in various aspects of cell–cell and cell–matrix interactions. To investigate the expression and distribution of the cell surface proteoglycans, syndecan-1 and -2, during periodontal wound healing, immunohistochemical analyses were carried out using monoclonal antibodies against syndecan-1, or -2 core proteins. Both syndecan-1 and -2 were expressed and distributed differentially at various stages of early inflammatory cell infiltration, granulation tissue formation, and tissue remodeling in periodontal wound healing. Expression of syndecan-1 was noted in inflammatory cells within and around the fibrin clots during the earliest stages of inflammatory cell infiltration. During granulation tissue formation it was noted in fibroblast-like cells and newly formed blood vessels. Syndecan-1 was not seen in newly formed bone or cementum matrix at any of the time periods studied. Syndecan-1 expression was generally less during the late stages of wound healing but was markedly expressed in cells that were close to the repairing junctional epithelium. In contrast, syndecan-2 expression and distribution was not evident at the early stages of inflammatory cell infiltration. During the formation of granulation tissue and subsequent tissue remodeling, syndecan-2 was expressed extracellularly in the newly formed fibrils which were oriented toward the root surface. Syndecan-2 was found to be significantly expressed on cells that were close to the root surface and within the matrix of repaired cementum covering root dentin as well as at the alveolar bone edge. These findings indicate that syndecan-1 and -2 may have distinctive functions during wound healing of the periodontium. The appearance of syndecan-1 may involve both cell–cell and cell–matrix interactions, while syndecan-2 showed a predilection to associate with cell–matrix interactions during hard tissue formation.

INT6/EIF3E interacts with ATM and is required for proper execution of the DNA damage response in human cells

Altered expression of the INT6 gene, encoding the e subunit of the translational initiation factor eIF3, occurs in human breast cancers, but how INT6 relates to carcinogenesis remains unestablished. Here, we show that INT6 is involved in the DNA damage response. INT6 was required for cell survival following γ-irradiation and G(2)-M checkpoint control. RNA interference-mediated silencing of INT6 reduced phosphorylation of the checkpoint kinases CHK1 and CHK2 after DNA damage. In addition, INT6 silencing prevented sustained accumulation of ataxia telangiectasia mutated (ATM) at DNA damage sites in cells treated with γ-radiation or the radiomimetic drug neocarzinostatin. Mechanistically, this result could be explained by interaction of INT6 with ATM, which together with INT6 was recruited to the sites of DNA damage. Finally, INT6 silencing also reduced ubiquitylation events that promote retention of repair proteins at DNA lesions. Accordingly, accumulation of the repair factor BRCA1 was defective in the absence of INT6. Our findings reveal unexpected and striking connections of INT6 with ATM and BRCA1 and suggest that the protective action of INT6 in the onset of breast cancers relies on its involvement in the DNA damage response.

Tag-based interaction in online and mobile banking : a preliminary study of the effect on usability

In this paper we describe tag-based interaction afforded by a tag-based interface in online and mobile banking, and present our preliminary usability evaluation findings. We conducted a pilot usability study with a group of banking users by comparing the present 'conventional' interface and tag-based interface. The results show that participants perceive the tag-based interface as more usable in both online and mobile contexts. Participants also rated the tag-based interface better despite their unfamiliarity and perceived it as more user-friendly. Additionally, the results highlight that tag-based interaction is more effective in the mobile context especially to inexperienced mobile banking users. This in turn could have a positive effect on the adoption and acceptance of mobile banking in general and also specifically in Australia. We discuss our findings in more detail in the later sections of this paper and conclude with a discussion on future work.