Proceedings of the 6th Knowledge Cities World Summit, KCWS 2013

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 ‘knowledge-based urban development’, is different from its traditional predecessor. With a much more balanced focus on all of the four key development domains – economic, spatial, institutional, and socio-cultural – 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 knowledgebased urban development is to produce a city purposefully designed to encourage the continuous production, circulation and commercialization 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 focused 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 sixth edition of KCWS – The 6th Knowledge Cities World Summit 2013 – 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 multifaceted dimensions and various scales of building a ‘knowledge city’ via ‘knowledge-based urban development’ paradigm by particularly focusing on the overall Summit theme of ‘Establishing Bridges’. 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 2013 with the wider research, governance, and practice communities the knowledge co-created 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, organizers 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. Also we thank Prof.Dr. Ahmet Ademoğlu, Rector of İstanbul Şehir University, for providing all the support for the Summit. We hope the papers in this proceeding will inspire and make a significant contribution to the research, governance, and practice circles.

Passive control of a biventricular assist device with compliant inflow cannulae

Rotary ventricular assist device (VAD) support of the cardiovascular system is susceptible to suction events due to the limited preload sensitivity of these devices. This may be of particular concern with rotary biventricular support (BiVAD) where the native, flow-balancing Starling response is diminished in both ventricles. The reliability of sensor and sensor-less based control systems which aim to control VAD flow based on preload have limitations and thus an alternative solution is desired. This study introduces a compliant inflow cannula (CIC) which could improve the preload sensitivity of a rotary VAD by passively altering VAD flow depending on preload. To evaluate the design, both the CIC and a standard rigid inflow cannula were inserted into a mock circulation loop to enable biventricular heart failure support using configurations of atrial and ventricular inflow, and arterial outflow cannulation. A range of left (LVAD) and right VAD (RVAD) rotational speeds were tested as well as step changes in systemic/pulmonary vascular resistance to alter relative preloads, with resulting flow rates recorded. Simulated suction events were observed, particularly at higher VAD speeds, during support with the rigid inflow cannula, while the CIC prevented suction events under all circumstances. The compliant section passively restricted its internal diameter as preload was reduced, which increased the VAD circuit resistance and thus reduced VAD flow. Therefore, a compliant inflow cannula could potentially be used as a passive control system to prevent suction events in rotary left, right and biventricular support.

Evaluation of inflow cannulation site for implantation of right-sided rotary ventricular assist device

Right heart dysfunction is one of the most serious complications following implantation of a left ventricular assist device (LVAD), often leading to the requirement for short or long term right ventricular support (RVAD). The inflow cannulation site induces major haemodynamic changes and so there is a need to optimize the site used depending on the patient's condition. Therefore, this study evaluated and compared the haemodynamic influence of right atrial (RAC) and right ventricular (RVC) inflow cannulation sites. An in-vitro, variable heart failure, mock circulation loop was used to compare RAC and RVC in mild and severe biventricular heart failure (BHF) conditions. In the severe BHF condition, higher ventricular ejection fraction (RAC: 13.6%, RVC: 32.7%) and thus improved heart chamber and RVAD washout was observed with RVC, which suggested this strategy might be preferable for long term support (ie. bridge to transplant or destination therapy) to reduce the risk of thrombus formation. In the mild BHF condition, higher pulmonary valve flow (RAC: 3.33 L/min, RVC: 1.97 L/min) and lower right ventricular stroke work (RAC: 0.10 W, RVC: 0.13 W) and volumes were recorded with RAC. These results indicate an improved potential for myocardial recovery, thus RAC should be chosen in this condition. This in-vitro study suggests that RVAD inflow cannulation site should be chosen on a patient-specific basis with a view to the support strategy to promote myocardial recovery or reduce the risk of long-term complications.

Bioequivalence of two tablet formulations of capecitabine and exploration of age, gender, body surface area, and creatinine clearance as factors influencing systemic exposure in cancer patients

Purpose: The objective of the study was to assess the bioequivalence of two tablet formulations of capecitabine and to explore the effect of age, gender, body surface area and creatinine clearance on the systemic exposure to capecitabine and its metabolites. Methods: The study was designed as an open, randomized two-way crossover trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 25 patients with solid tumors. On one day, the patients received four 500-mg tablets of formulation B (test formulation) and on the other day, four 500-mg tablets of formulation A (reference formulation). The washout period between the two administrations was between 2 and 8 days. After each administration, serial blood and urine samples were collected for up to 12 and 24 h, respectively. Unchanged capecitabine and its metabolites were determined in plasma using LC/MS-MS and in urine by NMRS. Results: Based on the primary pharmacokinetic parameter, AUC(0-∞) of 5'-DFUR, equivalence was concluded for the two formulations, since the 90% confidence interval of the estimate of formulation B relative to formulation A of 97% to 107% was within the acceptance region 80% to 125%. There was no clinically significant difference between the t(max) for the two formulations (median 2.1 versus 2.0 h). The estimate for C(max) was 111% for formulation B compared to formulation A and the 90% confidence interval of 95% to 136% was within the reference region 70% to 143%. Overall, these results suggest no relevant difference between the two formulations regarding the extent to which 5'-DFUR reached the systemic circulation and the rate at which 5'-DFUR appeared in the systemic circulation. The overall urinary excretions were 86.0% and 86.5% of the dose, respectively, and the proportion recovered as each metabolite was similar for the two formulations. The majority of the dose was excreted as FBAL (61.5% and 60.3%), all other chemical species making a minor contribution. Univariate and multivariate regression analysis to explore the influence of age, gender, body surface area and creatinine clearance on the log-transformed pharmacokinetic parameters AUC(0-∞) and C(max) of capecitabine and its metabolites revealed no clinically significant effects. The only statistically significant results were obtained for AUC(0-∞) and C(max) of intact drug and for C(max) of FBAL, which were higher in females than in males. Conclusion: The bioavailability of 5'-DFUR in the systemic circulation was practically identical after administration of the two tablet formulations. Therefore, the two formulations can be regarded as bioequivalent. The variables investigated (age, gender, body surface area, and creatinine clearance) had no clinically significant effect on the pharmacokinetics of capecitabine or its metabolites.

The safety profile of perflutren microsphere contrast echocardiography during rest and stress imaging : results from an Australian multicentre cohort

Background Contrast enhanced echocardiography (CEE) is utilised when sub-optimal image quality results in non-diagnostic echocardiograms. However, there have been numerous safety notices issued by regulatory authorities regarding rare but potentially serious adverse reactions (AR). This multi-centre, retrospective analysis was performed to assess the short-term safety of CEE in a broad range of indications. Methods All CEE performed over 58 months at three institutions were assessed for AR within 30 min. Results A total of 5956 CEE were performed in 5576 patients. A total of 4903 were stress CEE and 1053 resting CCE.Bolus administration in 5719, infusion in 237 cases; 89.9% of CCE were outpatients. Commonest CEE indication was functional stress testing (82.3%). There were 16 AR related to CEE (0.27%). All AR were mild, transient and all patients made a full recovery. No cases of serious anaphylaxis or death within 30 min of contrast administration. Comparing those with and without an AR, there were no significant differences in age, gender, BMI, LVEF, patient location, exam type or RVSP. There was a slightly increased likelihood of an AR during infusion versus bolus dosing (p = 0.02). Conclusion CEE is a safe investigation in a broad range of indications and clinical scenarios. AR are very rare, mild and transient.

Design of physiological control and magnetic levitation systems for a total artificial heart

Total Artificial Hearts are mechanical pumps which can be used to replace the failing natural heart. This novel study developed a means of controlling a new design of pump to reproduce physiological flow bringing closer the realisation of a practical artificial heart. Using a mathematical model of the device, an optimisation algorithm was used to determine the best configuration for the magnetic levitation system of the pump. The prototype device was constructed and tested in a mock circulation loop. A physiological controller was designed to replicate the Frank-Starling like balancing behaviour of the natural heart. The device and controller provided sufficient support for a human patient while also demonstrating good response to various physiological conditions and events. This novel work brings the design of a practical artificial heart closer to realisation.

Vascular remodeling in the internal mammary artery graft and association with in situ endothelin-1 and receptor expression

BACKGROUND: The vasoconstricting peptide endothelin-1 (ET-1) has been associated with atherosclerotic cardiovascular disease, vascular smooth muscle cell (VSMC) growth stimulation, and intimal thickening. ET-1 binds 2 receptor subtypes, endothelin A and B, and the ETA receptor mediates vasoconstriction and VSMC growth. This study aims to quantitatively assess arterial remodeling variables and compare them with changes in ET-1, ETA, and ETB expression in the internal mammary artery (IMA). METHODS AND RESULTS: Specimens from 55 coronary artery disease (CAD) patients (45 men, 10 women; mean age 65 years) and 14 control IMA specimens (from 7 men and 7 women; mean age 45 years) were collected. IMA cross sections were assessed by histochemical and immunohistochemical staining methods to quantify the levels of medionecrosis, fibrosis, VSMC growth, ET-1, ETA, ETB, and macrophage infiltration. The percentage area of medionecrosis in the patients was almost double that in the controls (31.85+/-14.52% versus 17.10+/-9.96%, P=0.0006). Total and type 1 collagen was significantly increased compared with controls (65.8+/-18.3% versus 33.7+/-13.7%, P=0.07, and 14.2+/-10.0% versus 4.8+/-2.8%, P=0.01, respectively). Despite ACE and/or statin therapy, ET-1 expression and cell cycling were significantly elevated in the patient IMAs relative to the controls (46.27+/-18.46 versus 8.56+/-8.42, P=0.0001, and 37.29+/-12.88 versus 11.06+/-8.18, P=0.0001, respectively). ETA and ETB staining was elevated in the patient vessels (46.88+/-11.52% versus 18.58+/-7.65%, P=0.0001, and 42.98+/-7.08% versus 34.73+/-5.20%, P=0.0067, respectively). A mild presence of macrophages was noted in all sections. CONCLUSIONS: Elevated distribution of collagen indicative of fibrosis coupled with increased cell cycling and high levels of ET-1 and ETA expression in the absence of chronic inflammation suggests altered IMA VSMC regulation is fundamental to the remodeling process.

Voltage quality improvement in distribution networks containing DERs using UPQC

Single phase distributed energy resources (DERs) can cause voltage rise along distribution feeder and power imbalance among the phases. Usually transformer tap setting are used to mitigate voltage drop along feeders. However this can aggravate the voltage rise problem when DERs are connected. Moreover if the power generation in a phase is more than its load demand, the excess power in that phase will be fed back to the transmission network. In this paper, a unified power quality compensator (UPQC) has been utilized to alleviate the voltage quality excess power circulation problems. Through analysis and simulation results, the mode of operation of UPQC is highlighted. The proposals are validated through extensive digital computer simulation studies using PSCAD and MATLAB.

Integrating 40Ar-39Ar, 87Rb-87Sr and 147Sm-143Nd geochronology of authigenic illite to evaluate tectonic reactivation in an intraplate setting, central Australia

The Warburton-Cooper basins, central Australia, include a multitude of reactivated fracture-fault networks related to a complex, and poorly understood, tectonic evolution. We investigated authigenic illites from a granitic intrusion and sedimentary rocks associated with prominent structural features (Gidgealpa-Merrimelia-Innamincka Ridge and the Nappamerri Trough). These were analysed by 40Ar-39Ar, 87Rb-87Sr and 147Sm-143Nd geochronology to explore the thermal and tectonic histories of central Australian basins. The combined age data provide evidence for three major periods of fault reactivation throughout the Phanerozoic. While Carboniferous (323.3 ± 9.4 Ma) and Late Triassic ages (201.7 ± 9.3 Ma) derive from basin-wide hydrothermal circulation, Cretaceous ages (~128 to ~86 Ma) reflect episodic fluid flow events restricted to the synclinal Nappamerri Trough. Such events result from regional extensional tectonism derived from the transferral of far-field stresses to mechanically and thermally weakened regions of the Australian continent. Specifically, Cretaceous ages reflect continent-wide transmission of tensional stress from a > 2500 km long rifting event on the Eastern (and southern) Australian margin associated with break-up of Gondwana and opening of the Tasman Sea. By integrating 40Ar-39Ar, 87Rb-87Sr and 147Sm-143Nd dating, this study highlights the use of authigenic illite in temporally constraining the tectonic evolution of intracontinental basins that would otherwise remain unknown. Furthermore, combining Sr- and Ar-isotopic systems enables more accurate dating of authigenesis whilst significantly reducing geochemical pitfalls commonly associated with these radioisotopic dating methods.

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.