63 research outputs found
A new chromogenic assay (HemosIL ThromboPath) is sensitive to major prothrombotic risk factors affecting the protein C pathway : results of a multicenter study
No full textThe HemosIL ThromboPath assay (Instrumentation Laboratory) is a new chromogenic assay designed to globally evaluate the functionality of the protein C (PC) pathway. It is based on the ability of endogenous APC generated after activation of PC by a snake venom extract (Protac) to reduce the thrombin generation induced by a reagent containing tissue factor. The aim of this multicenter study involving three laboratories was to evaluate the test sensitivity to PC pathway abnormalities by retrospectively testing frozen plasma samples obtained in the different laboratories. Test results were significantly lower (p < 0.0001) in subjects who presented with any confirmed PC pathway abnormality than in those without. The cut-off value, defined in each participating center as the mean value minus one standard deviation of test results obtained in 30 normal samples, was found to provide a sensitivity-to-specificity ratio similar to that obtained using ROC-analysis. The assay performed well in carriers of the factor V Leiden mutation (n = 81), patients with PC deficiency (n = 40), combined defects (n = 55) or lupus anticoagulant (n = 44), with test results below the locally defined cut-off values in 97.5%, 95.0%, 100% and 100% of the tested subjects, respectively. The assay sensitivity for PS deficiency (n = 62) was 87.1%. Only 13.6% of the 272 subjects without any PC pathway abnormality had a decreased test result. So, using the locally defined cut-off values, the overall test sensitivity to all tested PC pathway abnormalities was 95.0% (95%CI = 91.8-97.3), its specificity 86.4% (95%CI = 81.8-90.2), its negative predictive value 94.4% (95%CI = 90.8-96.9) and its positive predictive value 87.9% (95%CI = 83.7-91.3)
Hemosil ThromboPath : a chromogenic assay sensitive to major prothrombotic risk factors affecting the protein C pathway
No full textThe Live Creature and Ethereal Things: Physics in Culture
No full textThe Live Creature and Ethereal Things: Physics in Culture is a collection of texts, images and conversations that present fundamental physics and the physics of the universe as human activities and cultural endeavours.
Cosmology and particle physics probe the furthest limits of the knowable and have the potential to provide transcendental aesthetic and conceptual experiences, enriching our everyday lives. These explorations of the otherworldly and the ethereal are undertaken by human beings in real world laboratories and observatories. Yet in our Western European culture, physics tends to be represented as factual, abstract, “hard”, and removed from our lived human experience. This lack of a sense of how physics unfolds through its processes, personalities and places leads to a gap in the cultural imaginary and social understanding of physics, which also impacts on those who might choose to study this complex subject or go into it as a profession.
Featuring texts, images and conversations by physicists, artists and curators, the book examines the role of personality, power and culture in physics and discusses the value of cross-pollination between the practices of contemporary art and physics. These reflections shed light on the people and material practices of physics: from the vast underground particle physics laboratory at CERN, Geneva, used by half of the world’s particle physicists, and deep underground neutrino observatories in the UK, Italy and Antarctica, to super-computers that construct astonishing visualisations of the evolution of the universe
Art and Intervention in the Stewardship of the Planetary Commons: Towards a Curatorial Model of Co-inquiry
No full textThis Ph.D. by Published Work examines five projects that took place over ten years, between 2007 and 2016, that were curated as part of the artistic programme of Arts Catalyst,an independent interdisciplinary arts commissioning organisation of which the author is the founding director. This programme of work sought to understand what form of curatorial model and interpretative framework could generate new artworks and
co-produce interdisciplinary knowledge across areas of specialist research and geopolitical urgency.
The projects take the form of exhibitions, texts and edited books, which are presented as the portfolio of work. The selected projects are: Malamp UK, Brandon Ballengée (2007-2010); Arctic Perspective Initiative (2009-2011); ITACCUS – IAF Technical Activities Committee on the Cultural Utilisation of Space – and associated activities (2007-2014); Holoturian, Ariel Guzik (2013-2015); and Wrecked on the Intertidal Zone, YoHa, Critical Art Ensemble, et al. (2013-2016).
Through analysis of and reflection on the projects, this commentary proposes a curatorial model of interdisciplinary co-inquiry, which can foster an ecology of practices, enabling curators, artists, scientists, specialist experts and people with situated expertise to coproduce knowledge around matters of concern, particularly relating to human environment interaction and common and extraterritorial spaces. It examines the roles of the curator in this model and how these might differ from those commonly understood as established curatorial practice.
The commentary further presents an interpretative and tactical framework of the planetary commons for curating art-led projects in the realm of ecopolitical concerns, that can engage audiences and publics with the art and ideas emerging from this coinquiry approach. The combination of curatorial model and interpretative and tactical framework contribute to discourses on both inter/trans-disciplinarity and the role of art in relation to the politics of ecology.
The Ph.D. contributes to the field on several levels. Within curatorial studies, the interdisciplinary co-inquiry model reconfigures curatorial practice as a collective, inquiry3 driven, knowledge-producing practice, and provides a useful methodology for inter- /trans-disciplinary artistic practice in relation to the politics of ecology, while the framework of the planetary commons proposes direction and allows for investment in reciprocity through commoning practices. Beyond contemporary art, a curatorial coinquiry model deepens and alters existing approaches for listening to, valuing, and synthesising different types of knowledge and expertise around current environmental and related social concerns. While the commentary argues for the planetary commons framework within the contemporary art space, there are wider implications for it as a complement and alternative to the dominant interpretative framework of the Anthropocene
Beyond PI3Ks: targeting phosphoinositide kinases in disease.
No full textLipid phosphoinositides are master regulators of almost all aspects of a cell's life and death and are generated by the tightly regulated activity of phosphoinositide kinases. Although extensive efforts have focused on drugging class I phosphoinositide 3-kinases (PI3Ks), recent years have revealed opportunities for targeting almost all phosphoinositide kinases in human diseases, including cancer, immunodeficiencies, viral infection and neurodegenerative disease. This has led to widespread efforts in the clinical development of potent and selective inhibitors of phosphoinositide kinases. This Review summarizes our current understanding of the molecular basis for the involvement of phosphoinositide kinases in disease and assesses the preclinical and clinical development of phosphoinositide kinase inhibitors
Polo-like kinase 1 as a prognostic and therapeutic target in high-grade brain tumors
No full textHigh-grade brain tumors have some of the highest rates of cancer-related death. Occurring predominately in adults, patients with glioblastoma (GBM) are not expected to survive longer than two years. Similarly, medulloblastoma (MB) is the most commonly occurring malignant brain tumor in children and, although these cases have a much better probability of survival, the severe impact of high-intensity treatment often causes long-term negative side effects. Unfortunately, high-grade brain tumors are frequently resistant to standard treatments like temozolomide (TMZ). Further, the development of new drugs is hindered by the blood-brain barrier and the astronomical cost of drug discovery and clinical evaluation. The immediate need for new treatment options encouraged our approach of querying compounds that have previously been tested in clinical trials. Herein, we found that TMZ resistant GBM cells express high levels of the mitotic kinase, Polo-Like Kinase 1 (PLK1) and that TMZ resistance can be overcome using PLK1 kinase inhibitors, such as BI-2536. An assessment of off-patent drugs revealed that the anti-alcoholism treatment, disulfiram (DSF), also had efficacy in eliminating PLK1-high cells and this work proposes DSF can be repurposed for cancer treatment. The importance of PLK1 was further investigated in a retrospective study of MB patient samples that were assessed with the NanoString nCounter system. Cases with high PLK1 expression were more likely to relapse and had worse overall survival. This work suggests that stratification of these high-risk cases can identify patients that may benefit from PLK1 inhibitors, which cause G2/M arrest and apoptosis. Notably, both DSF and BI-2536 treatment had no negative growth effects on normal brain cells. Finally, translationally controlled tumor protein (TCTP) is a substrate of PLK1 that is used as a marker of kinase activity. An exploration of the clinical and mechanistic impact of TCTP demonstrated a striking association with the sonic hedgehog (SHH) MB subtype, as well, as establishing its role in cancer cell proliferation. In conclusion, the studies outlined in this thesis encourage the investigation of PLK1 as a therapeutic target in high-grade brain tumors and emphasizes the potential benefit of fighting cancer with repurposed drugs.Medicine, Faculty ofMedicine, Department ofGraduat
Emerg Infect Dis
No full textHuman and mouse prion proteins share a structural motif that regulates resistance to common chronic wasting disease (CWD) prion strains. Successful transmission of an emergent strain of CWD prion, H95(+), into mice resulted in infection. Thus, emergent CWD prion strains may have higher zoonotic potential than common strains
Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine
No full textPrecision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial. Because genomics alone was insufficient to identify therapeutic options for the majority of patients with advanced disease, we used high-throughput drug screening to discover effective treatment strategies. Analysis of tumor-derived cells from four cases, two uterine malignancies and two colon cancers, identified effective drugs and drug combinations that were subsequently validated using 3-D cultures and PDX models. This platform thereby promotes the discovery of novel therapeutic approaches that can be assessed in clinical trials and provides personalized therapeutic options for individual patients where standard clinical options have been exhausted.Significance: Integration of genomic data with drug screening from personalized in vitro and in vivo cancer models guides precision cancer care and fuels next-generation research. Cancer Discov; 7(5); 462-77. ©2017 AACR.See related commentary by Picco and Garnett, p. 456This article is highlighted in the In This Issue feature, p. 443
The distribution of group B streptococcal serotypes among isolates obtained in three Australian cities
No full textLaboratory scale production of serotyping antisera for group B streptococci, and comments on their use
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