The silent and apparent neurological injury in transcatheter aortic valve implantation study (SANITY) : concept, design and rationale

Background The incidence of clinically apparent stroke in transcatheter aortic valve implantation (TAVI) exceeds that of any other procedure performed by interventional cardiologists and, in the index admission, occurs more than twice as frequently with TAVI than with surgical aortic valve replacement (SAVR). However, this represents only a small component of the vast burden of neurological injury that occurs during TAVI, with recent evidence suggesting that many strokes are clinically silent or only subtly apparent. Additionally, insult may manifest as slight neurocognitive dysfunction rather than overt neurological deficits. Characterisation of the incidence and underlying aetiology of these neurological events may lead to identification of currently unrecognised neuroprotective strategies. Methods The Silent and Apparent Neurological Injury in TAVI (SANITY) Study is a prospective, multicentre, observational study comparing the incidence of neurological injury after TAVI versus SAVR. It introduces an intensive, standardised, formal neurologic and neurocognitive disease assessment for all aortic valve recipients, regardless of intervention (SAVR, TAVI), valve-type (bioprosthetic, Edwards SAPIEN-XT) or access route (sternotomy, transfemoral, transapical or transaortic). Comprehensive monitoring of neurological insult will also be recorded to more fully define and compare the neurological burden of the procedures and identify targets for harm minimisation strategies. Discussion The SANITY study undertakes the most rigorous assessment of neurological injury reported in the literature to date. It attempts to accurately characterise the insult and sustained injury associated with both TAVI and SAVR in an attempt to advance understanding of this complication and associations thus allowing for improved patient selection and procedural modification.

Repair and regeneration of osteochondral defects in the articular joints

People suffering from pain due to osteoarthritic or rheumatoidal changes in the joints are still waiting for a better treatment. Although some studies have achieved success in repairing small cartilage defects, there is no widely accepted method for complete repair of osteochondral defects. Also joint replacements have not yet succeeded in replacing of natural cartilage without complications. Therefore, there is room for a new medical approach, which outperforms currently used methods. The aim of this study is to show potential of using a tissue engineering approach for regeneration of osteochondral defects. The critical review of currently used methods for treatment of osteochondral defects is also provided. In this study, two kinds of hybrid scaffolds developed in Hutmacher's group have been analysed. The first biphasic scaffold consists of fibrin and PCL. The fibrin serves as a cartilage phase while the porous PCL scaffold acts as the subchondral phase. The second system comprises of PCL and PCL-TCP. The scaffolds were fabricated via fused deposition modeling which is a rapid prototyping system. Bone marrow-derived mesenchymal cells were isolated from New Zealand White rabbits, cultured in vitro and seeded into the scaffolds. Bone regenerations of the subchondral phases were quantified via micro CT analysis and the results demonstrated the potential of the porous PCL and PCL-TCP scaffolds in promoting bone healing. Fibrin was found to be lacking in this aspect as it degrades rapidly. On the other hand, the porous PCL scaffold degrades slowly hence it provides an effective mechanical support. This study shows that in the field of cartilage repair or replacement, tissue engineering may have big impact in the future. In vivo bone and cartilage engineering via combining a novel composite, biphasic scaffold technology with a MSC has been shown a high potential in the knee defect regeneration in the animal models. However, the clinical application of tissue engineering requires the future research work due to several problems, such as scaffold design, cellular delivery and implantation strategies.

Reliability analysis and economic equipment replacement appraisal for substation and sub-transmission systems with explicit inclusion of non-repairable failures

The modern society has come to expect the electrical energy on demand, while many of the facilities in power systems are aging beyond repair and maintenance. The risk of failure is increasing with the aging equipments and can pose serious consequences for continuity of electricity supply. As the equipments used in high voltage power networks are very expensive, economically it may not be feasible to purchase and store spares in a warehouse for extended periods of time. On the other hand, there is normally a significant time before receiving equipment once it is ordered. This situation has created a considerable interest in the evaluation and application of probability methods for aging plant and provisions of spares in bulk supply networks, and can be of particular importance for substations. Quantitative adequacy assessment of substation and sub-transmission power systems is generally done using a contingency enumeration approach which includes the evaluation of contingencies, classification of the contingencies based on selected failure criteria. The problem is very complex because of the need to include detailed modelling and operation of substation and sub-transmission equipment using network flow evaluation and to consider multiple levels of component failures. In this thesis a new model associated with aging equipment is developed to combine the standard tools of random failures, as well as specific model for aging failures. This technique is applied in this thesis to include and examine the impact of aging equipments on system reliability of bulk supply loads and consumers in distribution network for defined range of planning years. The power system risk indices depend on many factors such as the actual physical network configuration and operation, aging conditions of the equipment, and the relevant constraints. The impact and importance of equipment reliability on power system risk indices in a network with aging facilities contains valuable information for utilities to better understand network performance and the weak links in the system. In this thesis, algorithms are developed to measure the contribution of individual equipment to the power system risk indices, as part of the novel risk analysis tool. A new cost worth approach was developed in this thesis that can make an early decision in planning for replacement activities concerning non-repairable aging components, in order to maintain a system reliability performance which economically is acceptable. The concepts, techniques and procedures developed in this thesis are illustrated numerically using published test systems. It is believed that the methods and approaches presented, substantially improve the accuracy of risk predictions by explicit consideration of the effect of equipment entering a period of increased risk of a non-repairable failure.

Application of Mesenchymal Stem Cells for repair and regeneration of cartilage and bone

Australian efforts to provide orthopaedic surgeons with living, load-bearing scaffolds suitable for current joint (knee and hip) replacement surgery, non-union fracture repair, and miniscal and growth plate cartilage regeneration are being lead by teams at the Institute for Medical and Veterinary Science and Women's and Children's Hospital in Adelaide; the Peter MacCallum and St Vincent's Medical Research Institutes in Melbourne; and the Mater Medical Research Institute and new Institute for Health and Biomedical Innovation at QUT, Brisbane. In each case multidisciplinary teams are attempting to develop autologous living tissue constructs, utilising mesenchymal stem cells (MSC), with the intention of effecting seamless repair and regeneration of skeletal trauma and defects. In this article we will briefly review current knowledge of the phenotypic properties of MSC and discuss the potential therapeutic applications of these cells as exemplified by their use in cartilage repair and tissue engineering based approaches to the treatment of skeletal defects.

Mesenchymal stromal cells and the repair of cartilage tissue

Articular cartilage has a limited intrinsic repair capacity, and thus defects are more likely to further degrade rather than undergo spontaneous self-repair. Whilst a number of surgical techniques have been developed to repair cartilage defects, their efficacy is generally poor and total joint replacement remains the gold standard, albeit last resort, treatment option. Cell-based therapies hold the greatest promise, as they appear uniquely capable of generating de novo cartilage tissue. Two approved therapies (ACI and MACI) are based on the premise that the transplantation of ex vivo expanded autologous chondrocyte populations, harvested from a non-load bearing region of the same joint, could be utilized to effectively regenerate cartilage tissue in the primary defect site. These therapeutic strategies are partially limited by our inability to harvest and expand adequate numbers of autologous chondrocytes that retain the appropriate phenotype. By contrast, the harvest and expansion of large numbers of mesenchymal stem/stromal cells (MSC) derived from tissues such as bone marrow and adipose is comparatively straightforward and has become routine in laboratories worldwide. Additionally, our understanding of the biochemical and biophysical signals required to drive the chondrogenic differentiation of MSC is rapidly increasing. It is conceivable that in the near future MSC expansion and differentiation technologies will offer a means to generate sufficient cell numbers, of an appropriate phenotype, for use in cartilage defect repair. In this chapter we review the relative potential of MSC and their likely contribution to cartilage regeneration.

Exploring methods of preparing functional cartilage-bone xenografts for joint repair

This thesis explores the feasibility of donor-receiver concept for joint replacement where cartilage-bone tissues can be taken from either human or other mammals and prepared scientifically for repairing focal joint defects in knees, hips and shoulders. The manufactured construct is immunologically inert and is capable of acting as a scaffold for engineering new cartilage-bone laminates when placed in the joint. Innovative manufacturing procedures and assessment techniques were developed for appraising this tissue-based scaffold. This research has demonstrated that tissue replacement technology can be applied in situations where blood vessels are absent such as in articular cartilage.

Clinically indicated replacement versus routine replacement of peripheral venous catheters (Review)

Background Centers for Disease Control Guidelines recommend replacement of peripheral intravenous (IV) catheters every 72 to 96 hours. Routine replacement is thought to reduce the risk of phlebitis and bacteraemia. Catheter insertion is an unpleasant experience for patients and replacement may be unnecessary if the catheter remains functional and there are no signs of inflammation. Costs associated with routine replacement may be considerable. Objectives To assess the effects of removing peripheral IV catheters when clinically indicated compared with removing and re-siting the catheter routinely.