Increased generation of platelet-derived microparticles following percutaneous transluminal coronary angioplasty

Platelet-derived microparticles (PMPs) which are produced during platelet activation contribute to coagulation1 and bind to traumatized endothelium in an animal model2. Such endothelial injury occurs during percutaneous transluminal coronary angioplasty (PTCA), a procedure which restores the diameter of occluded coronary arteries using balloon inflations. However, re-occlusions subsequently develop in 20-25% of patients3, although this is limited by treatment with anti-platelet glycoprotein IIb/IIIa receptor drugs such as abciximab4. However, abciximab only partially decreases the need for revascularisation5, and therefore other mechanisms appear to be involved. As platelet activation occurs during PTCA, it is likely that PMPs may be produced and contribute to restenosis. This study population consisted of 113 PTCA patients, of whom 38 received abciximab. Paired peripheral arterial blood samples were obtained from the PTCA sheath: 1) following heparinisation (baseline); and 2) subsequent to all vessel manipulation (post-PTCA). Blood was prepared with an anti-CD61 (glycoprotein IIIa) fluorescence conjugated antibody to identify PMPs using flow cytometry, and PMP results expressed as a percentage of all CD61 events. The level of PMPs increased significantly from baseline following PTCA in the without abciximab group (paired t test, P=0.019). However, there was no significant change in the level of PMPs following PTCA in patients who received abciximab. Baseline clinical characteristics between patient groups were similar, although patients administered abciximab had more complex PTCA procedures, such as increased balloon inflation pressures (ANOVA, P=0.0219). In this study, we have clearly demonstrated that the level of CD61-positive PMPs increased during PTCA. This trend has been demonstrated previously, although a low sample size prevented statistical significance being attained6. The results of our work also demonstrate that there was no increase in PMPs after PTCA with abiciximab treatment. The increased PMPs may adhere to traumatized endothelium, contributing to re-occlusion of the arteries, but this remains to be determined. References: (1) Holme PA, Brosstad F, Solum NO. Blood Coagulation and Fibrinolysis. 1995;6:302-310. (2) Merten M, Pakala R, Thiagarajan P, Benedict CR. Circulation. 1999;99:2577-2582. (3) Califf RM. American Heart Journal.1995;130:680-684. (4) Coller BS, Scudder LE. Blood. 1985;66:1456-1459. (5) Topol EJ, Califf RM, Weisman HF, Ellis SG, Tcheng JE, Worley S, Ivanhoe R, George BS, Fintel D, Weston M, Sigmon K, Anderson KM, Lee KL, Willerson JT on behalf of the EPIC investigators. Lancet. 1994;343:881-886. (6) Scharf RE, Tomer A, Marzec UM, Teirstein PS, Ruggeri ZM, Harker LA. Arteriosclerosis and Thrombosis. 1992;12:1475-87.

IODP Expedition 339 in the Gulf of Cadiz and off West Iberia : decoding the environmental significance of the Mediterranean outflow water and its global influence

IODP Expedition 339 drilled five sites in the Gulf of Cadiz and two off the west Iberian margin (November 2011 to January 2012), and recovered 5.5 km of sediment cores with an average recovery of 86.4%. The Gulf of Cadiz was targeted for drilling as a key location for the investigation of Mediterranean outflow water (MOW) through the Gibraltar Gateway and its influence on global circulation and climate. It is also a prime area for understanding the effects of tectonic activity on evolution of the Gibraltar Gateway and on margin sedimentation. We penetrated into the Miocene at two different sites and established a strong signal of MOW in the sedimentary record of the Gulf of Cadiz, following the opening of the Gibraltar Gateway. Preliminary results show the initiation of contourite deposition at 4.2–4.5 Ma, although subsequent research will establish whether this dates the onset of MOW. The Pliocene succession, penetrated at four sites, shows low bottom current activity linked with a weak MOW. Significant widespread unconformities, present in all sites but with hiatuses of variable duration, are interpreted as a signal of intensified MOW, coupled with flow confinement. The Quaternary succession shows a much more pronounced phase of contourite drift development, with two periods of MOW intensification separated by a widespread unconformity. Following this, the final phase of drift evolution established the contourite depositional system (CDS) architecture we see today. There is a significant climate control on this evolution of MOW and bottom-current activity. However, from the closure of the Atlantic–Mediterranean gateways in Spain and Morocco just over 6 Ma and the opening of the Gibraltar Gateway at 5.3 Ma, there has been an even stronger tectonic control on margin development, downslope sediment transport and contourite drift evolution. The Gulf of Cadiz is the world's premier contourite laboratory and thus presents an ideal testing ground for the contourite paradigm. Further study of these contourites will allow us to resolve outstanding issues related to depositional processes, drift budgets, and recognition of fossil contourites in the ancient record on shore. The expedition also verified an enormous quantity and extensive distribution of contourite sands that are clean and well sorted. These represent a relatively untapped and important exploration target for potential oil and gas reservoirs.

Psychological symptoms : a review of screening practices for patients with coronary heart disease (CHD)

Background/Aims: Coronary heart disease (CHD) and coronary events have been strongly linked to psychological symptoms in patients during hospitalisation and post-discharge. Within Australia CHD average length of stay is decreasing and symptoms often do not present until discharge. Early screening and treatment of psychological symptoms has been recommended to reduce mortality and identify anxiety and depression. This literature review was undertaken to evaluate and describe current screening practices to identify psychological symptoms in these patients.

Cancer : the to and fro of tumour spread

The spread of cells from the primary site of a solid tumour to distant sites remains the major cause of disease and death associated with these cancers. For tumour cells to spread, or metastasize, they must modify their 'anchored' state and detach from their neighbouring cells; migrate through tissues into the blood and lymph systems; survive in these circulation systems; and then leave the vessels at an appropriate site to form another tumour1. Many of these events are favoured by conversions between two cellular states — the epithelial and mesenchymal phenotypes. But the role of these transitions in cancer metastasis is controversial. Writing in Cancer Cell, Tsai et al.2 and Ocaña et al.3 help to clarify this issue...

Assessment of angiogenic potential--the use of AIDS-KS cell supernatants as an in vitro model

Metastasis, the passage of primary tumour cells throughout the body via the vascular system and their subsequent proliferation into secondary lesions in distant organs, represents a poor prognosis and therefore an understandably feared event for cancer patients. Despite considerable advances in cancer diagnosis and treatment, most deaths are the result of metastases resistant to conventional treatment [1]. Rather than being a random process, metastasis involves a series of organised steps leading to the growth of a secondary tumour. Malignant tumours stimulate the production of new vessels by the host, and this process is a prerequisite for the increase in size of a new tumour [2]. Angiogenesis, not only permits tumour expansion but also allows the entry of tumour cells into the circulation and is probably the most vital event for the metastatic process [3]. Metastasis and angiogenesis [4] have received much attention in recent years. A biological understanding of both phenomena seems to be an urgent priority towards the search for an effective prevention and treatment of tumour progression. Studies in vitro and in vivo have shown that one of the most important barriers to the passage of malignant cells is the basement membrane. The crossing of such barriers is a vital step in the formation of a metastasis [5].

Endothelial precursor cells home to a vascularized tissue engineering chamber by application of the angiogenic chemokine CXCl12

Tissue engineering of vascularized constructs has great utility in reconstructive surgery. While we have been successful in generating vascularized granulation-like tissue and adipose tissue in an in vivo tissue engineering chamber, production of other differentiated tissues in a stable construct remains a challenge. One approach is to utilize potent differentiation factors, which can influence the base tissue. Endothelial precursor cells (EPCs) have the ability to both carry differentiation factors and home to developing vasculature. In this study, proof-of-principle experiments demonstrate that such cells can be recruited from the circulation into an in vivo tissue engineering chamber. CXC chemokine ligand 12 (CXCL12)/stromal cell-derived factor 1 was infused into the chamber through Alzet osmotic pumps and chamber cannulation between days 0 and 7, and facilitated recruitment of systemically inoculated exogenous human EPCs injected on day 6. CXCL12 infusion resulted in an eightfold increase in EPC recruitment, 2 (p = 0.03) and 7 days postinfusion (p = 0.008). Delivery of chemotactic/proliferation and/or differentiation factors and appropriately timed introduction of effective cells may allow us to better exploit the regenerative potential of the established chamber construct. © Copyright 2009, Mary Ann Liebert, Inc. 2009.

The 4th Knowledge Cities World Summit Proceedings

FROM KCWS 2011 CHAIRS AND SUMMIT PROCEEDING EDITORS In recent years, with the impact of global knowledge economy, a more comprehensive development approach has gained significant popularity. This new development approach, so called ‘knowledgebased development’, is different from its traditional predecessor. With a much more balanced focus on all of the four key development domains – economic, enviro-urban, institutional, and sociocultural – this contemporary approach, aims to bring economic prosperity, environmental sustainability and local institutional competence with a just socio-spatial order to our cities and regions. The ultimate goal of knowledge-based development is to produce a city purposefully designed to encourage the continuous production, circulation and commercialisation of social and scientific knowledge – this will in turn establish a ‘knowledge city’. A city following the ‘knowledge city’ concept embarks on a strategic mission to firmly encourage and nurture locally focussed innovation, science and creativity within the context of an expanding knowledge economy and society. In this regard a ‘knowledge city’ can be seen as an integrated city, which physically and institutionally combines the functions of a science and technology park with civic and residential functions and urban amenities. It also offers one of the effective paradigms for the sustainable cities of our time. This fourth edition of KCWS – The 4th Knowledge Cities World Summit 2011 – makes an important reminder that the 'knowledge city' concept is a key notion in the 21st Century development. Considering this notion, the Summit sheds light on the multi-faceted dimensions and various scales of building a ‘knowledge city’ via 'knowledge-based development' paradigm by particularly focusing on the overall Summit theme of ‘Knowledge Cities for Future Generations’. At this summit, the theoretical and practical maturing of knowledge-based development paradigms are advanced through the interplay between the world’s leading academics’ theories and the practical models and strategies of practitioners’ and policy makers’ drawn from around the world. This summit proceeding is compiled in order to disseminate the knowledge generated and shared in KCWS 2011 with the wider research, governance, and practice communities the knowledge cocreated in this summit. All papers of this proceeding have gone through a double-blind peer review process and been reviewed by our summit editorial review and advisory board members. We, organisers of the summit, cordially thank the members of the Summit Proceeding Editorial Review and Advisory Board for their diligent work in the review of the papers. We hope the papers in this proceeding will inspire and make a significant contribution to the research, governance, and practice circles.

Requiem for a beast : a case study in controversy

In 2008, Matt Ottley’s Requiem for a Beast: A Work for Image, Word and Music was awarded the Book of the Year: Picture Book by the Children’s Book Council of Australia (CBCA). Ottley’s book is challenging in its form and content: it uses words, illustrations, and music to tell a sustained, multi-layered narrative about one young man’s attempts to reconcile his family’s and his nation’s shameful history of violence against Aboriginal Australians, while also coming to terms with his own attempts to commit suicide. Given the ways in which the CBCA’s annual book awards are used by teachers, librarians, and parents to select the “best” books for young readers, it is unsurprising that the prizing of Requiem for a Beast stirred up controversy. Responses to the book proliferated across professional and popular outlets—it even received coverage on an Australian tabloid television program—and initiated a variety of conversations about what constitutes appropriate reading for young people. Perhaps more significantly, the controversy over Requiem winning picture book of the year forced the CBCA, teacher librarians, and caregivers to examine (and, often, defend) their roles and responsibilities in the circulation and promotion of children’s literature. This paper reads the Requiem controversies as a case study for understanding the complementary and contradictory roles of institutions and individuals in the ethical circulation of children’s literature in contemporary Australia and beyond.

Onset of Mediterranean outflow into the North Atlantic

Sediments cored along the southwestern Iberian margin during Integrated Ocean Drilling Program Expedition 339 provide constraints on Mediterranean Outflow Water (MOW) circulation patterns from the Pliocene epoch to the present day. After the Strait of Gibraltar opened (5.33 million years ago), a limited volume of MOW entered the Atlantic. Depositional hiatuses indicate erosion by bottom currents related to higher volumes of MOW circulating into the North Atlantic, beginning in the late Pliocene. The hiatuses coincide with regional tectonic events and changes in global thermohaline circulation (THC). This suggests that MOW influenced Atlantic Meridional Overturning Circulation (AMOC), THC, and climatic shifts by contributing a component of warm, saline water to northern latitudes while in turn being influenced by plate tectonics.

Critical dependence of blood-borne biomarker concentrations on the half-lives of their carrier proteins

Until recently, the low-abundance (LA) range of the serum proteome was an unexplored reservoir of diagnostic information. Today it is increasingly appreciated that a diagnostic goldmine of LA biomarkers resides in the blood stream in complexed association with more abundant higher molecular weight carrier proteins such as albumin and immunoglobulins. As we now look to the possibility of harvesting these LA biomarkers more efficiently through engineered nano-scale particles, mathematical approaches are needed in order to reveal the mechanisms by which blood carrier proteins act as molecular 'mops' for LA diagnostic cargo, and the functional relationships between bound LA biomarker concentrations and other variables of interest such as biomarker intravasation and clearance rates and protein half-lives in the bloodstream. Here we show, by simple mathematical modeling, how the relative abundance of large carrier proteins and their longer half-lives in the bloodstream work together to amplify the total blood concentration of these tiny biomarkers. The analysis further suggests that alterations in the production of biomarkers lead to gradual rather than immediate changes in biomarker levels in the blood circulation. The model analysis also points to the characteristics of artificial nano-particles that would render them more efficient harvesters of tumor biomarkers in the circulation, opening up possibilities for the early detection of curable disease, rather than simply better detection of advanced disease.

The amplified peptidome : the new treasure chest of candidate biomarkers

Mass spectrometric analysis of the low-molecular weight (LMW) range of the serum/plasma proteome is revealing the existence of large numbers of previously unknown peptides and protein fragments predicted to be derived from low- abundance proteins. This raises the question of why such low abundance molecules would be retained at detectable levels in the circulation, instead of being rapidly cleared and excreted. Theoretical models of biomarker production and association with serum carrier proteins have been developed to elucidate the mechanisms governing biomarker half-life in the bloodstream. These models predict that the vast majority of LMW biomarkers exist in association with circulating high molecular mass carrier proteins. Moreover, the total serum/ plasma concentration of the biomarker is largely determined by the clearance rate of the carrier protein, not the free-phase biomarker clearance itself. These predictions have been verified experimentally using molecular mass fractionation of human serum before mass spectrometry sequence analysis. These principles have profound implications for biomarker discovery and measurement.

Visions and values : the Children’s Book Council of Australia’s prizing of picture books in the twenty-first century

The Children’s Book Council of Australia (CBCA) administers the oldest national prize for children’s literature in Australia. Each year, the CBCA confers “Book of the Year” awards to literature for young people in five categories. In 2001, the establishment of an “Early Childhood” category opened up the venerable “Picture Book” category (first awarded in 1955) to books with an implied readership up to 18 years of age. As a result, this category has emerged in recent years as a highly visible space within which the CBCA can contest discourses of cultural marginalisation insofar as Australian (“colonial”) literature is constructed as inferior or adjunct to the major Anglophone literary traditions, and the consistent identification of children’s literature (and, indeed, of children) as lesser than its ‘adult’ counterparts. The CBCA is engaged in defining, evaluating, and legitimising a tradition of Australian children’s literature which is underpinned by a canonical impulse, and is a reflexive practice of self-definition, self-evaluation and self-legitimisation for the CBCA itself. While it is obviously problematic to identify award winners as a canon, it is equally obvious that literary prizing is a cultural practice derived from the logic of canonicity. In his discussion of the United States’s Newbery Medal, Kenneth Kidd notes that “Medal books are instant classics, the selection process an ostensible simulation of the test of time” (169) and that “the Medal is part of the canonical architecture of children's literature” (169). Thus, it is instructive to consider the visions and values of the national, of the social, and of the literary-aesthetic, in the picture books chosen by the Children’s Book Council of Australia (CBCA) as the “best” of the early twenty-first century. These books not only constitute a kind of canon for contemporary Australian children’s literature, but may well come to define what contemporary Australian children’s literature means in the wider literary field. The Book of the Year: Picture Book awards given by the CBCA since 2001 demonstrate that it is not only true of the Booker Prize that, “The choices of winning books reflect not only on the books themselves, then, but also back on the Prize, affecting its reputation and creating journalistic capital which is vital for the Prize to achieve its prominence and impact.” (81). Many of the twenty-first century CBCA award-winning picture books complicate traditional or comfortable understanding of Australianness, children’s literature, or “appropriate” modes of form and content, reminding us that “moments when texts resist or complicate recuperation into national discourses offer fruitful points for exploring the relationships between text and celebratory context” (Roberts 6). The CBCA has taken the opportunities offered by the liberation of the Picture Book category from an implied readership to challenge dominant constructions of children’s literature in Australia, and in so doing, are engaged in overt practices of canonicity with potentially long-lasting effects. Works Cited: Kidd, Kenneth. “Prizing Children’s Literature: The Case of Newbery Gold.” Children's Literature 35 (2007): 166-190. Roberts, Gillian. Prizing Literature: The Celebration and Circulation of National Culture. Toronto: U Toronto P, 2011. Squires, Claire. “Book Marketing and the Booker Prize.” Judging a Book by Its Cover: Fans, Publishers, Designers, and the Marketing of Fiction. Eds. Nicole Matthews and Nickianne Moody. Aldershot: Ashgate, 2007. 71-82.