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No description available.

Active constraints are collaborative human-robot control algorithms which have a well-established history of use within robot assisted surgery research. This control strategy anisotropically regulates the motion of a human user in such a way that it effectively combines the competencies of surgeons and robots, allowing for improved clinical outcomes and surgeon experience. The significant majority of research previously presented for active constraints focuses on their application to static procedures, where the surgical environment is assumed to be rigid throughout. In this thesis, several research contributions are presented which assist with applying active constraints in surgical procedures within deforming soft tissue. The primary contribution is the formulation of a novel haptic control algorithm, based on friction, which can effectively guide a surgeon in both positioning and orienting a surgical instrument, while guaranteeing that the haptic interaction is energetically dissipative. The proven dissipative formulation of these 'dynamic frictional constraints' ensures that the surgeon always has overall control of a procedure and makes the system resilient to limitations and errors in the robot's comprehension of the surgical environment. To apply active constraints within deforming tissue, it is necessary to compute the geometric relationship between the surgical instruments and the constrained anatomy. A novel bounding volume is proposed which, when used in a hierarchy, exploits the limits of soft tissue deformations to increase the resolution of constraint geometries that can be used at stable control rates. The experimental validation of these research contributions in a clinically realistic nerve dissection simulation and in non-clinical dynamic path-following tasks, shows significant benefits to the user in several metrics characterising surgical accuracy and precision. These results demonstrate that the proposed enhancements of active constraints could lead to increased surgeon performance, fewer complications and improved clinical outcomes in soft tissue surgical procedures.

Transplantation is often the only therapy for end-stage organ failure. Blood-borne leukocytes are guided into the grafts by proinflammatory chemokines. To achieve full functionality, chemokines interact with heparan sulphate (HS) proteoglycans, which are expressed on the majority of all animal cell surfaces, predominantly on the endothelium. Due to the modification, especially sulphation status of HS, chemokine function can be controlled. This study was designed to examine the expression of different HS epitopes during allograft rejection, dynamic changes of HS following experimental inflammation and investigate the regulation of HS biosynthesis, providing new targets for therapeutic intervention. Human renal and hepatic allografts expressed distinct HS epitopes which were indicative for the stage of rejection. In both organs, N-sulphated HS domains were elevated during acute phases of rejection whereas 2-O- and 6-O-sulphation increased significantly during chronic stages. The HS motif investigated could be matched to selective HS ligands based on essential target modifications. Data from transplant tissues was largely confirmed by in vitro studies simulating an inflammatory response employing relevant cell lines and N-deacetylase/N-sulphotransferase (NDST1) transfectants. Investigations of the regulation of HS biosynthesis at the protein level were carried out using tandem affinity purification. It revealed an interaction of NDST1, the key enzyme in HS biosynthesis, and beta tubulin. This interaction could provide an insight into general Golgi localisation and retention of glycosylation enzymes. This study substantiates the strategy of targeting heparan sulphate proteoglycans in inflammation and organ rejection, as distinct changes in HS epitope expression dependent of the stage of rejection were identified. During renal rejection, these specific HS species could be used as a biomarker giving evidence about the progression of the disease. Overall, this could lead to a Abstract novel anti-inflammatory therapy targeting an array of proinflammatory cytokines with less side affects compared to current treatment options.

Advances in surgical technology, critical care and antimicrobial therapy have improved outcomes for patients undergoing major abdominal surgery. However, for some patients, the risk of complications remains considerably high. It is recognised that sepsis due to bacterial infection is a major aetiological factor leading to postoperative major organ dysfunction. Current therapies to combat rates of infection rely far too heavily on antibiotics, to which there is growing resistance, leading to the demand for novel or alternative strategies The aim of this series of studies was to demonstrate the influence of bacteria and their products on human immune responses in both health and surgical disease. Previous studies indicate a potential role for probiotic bacteria in the treatment of infective disorders of the gastrointestinal tract. In this thesis, it is demonstrated using meta-analytical methods, that probiotic and synbiotic bacteria reduce the risk of infective complications following major abdominal surgery. It is proposed that some of the beneficial effects of probiotics involve modulation of host immune responses. In this thesis, it is demonstrated that probiotic treatment in healthy volunteers confers changes in the expression of Foxp3, the transcription factor characteristic of T regulatory cells. In addition, expression of cell surface proteins on dendritic cells (DCs) following synbiotic treatment has indicated expansion of mature DC subsets with altered phenotype.

Purpose - The Hong Kong Government in 2003 introduced a systemic change in its funding policy for Associate Degree programmes which removed funding from previously funded programmes, affecting 3,800 student places and some 150 teaching and support staff of the College of the case institution. The present study aims to explore, through a micro-political perspective, how the institution shaped its original response to this change, which was modified by a range of micro-political factors culminating in a final response negotiated by the management, the College staff and the governing body. In studying the case the research developed a „micro-political toolkit‟ comprising five core concepts: interests, conflict, groups and coalitions, power and bargaining, Design/methodology/approach - This study employed a qualitative case study research strategy. Qualitative semi-structured interviews were conducted with 10 interviewees and the data collected was triangulated with official documents. Findings - The case evidence supported further development of the five concepts in the „toolkit‟ to help better explain how the institution managed change. This included exposing the tension between professional and personal interests of teachers and developing a „hierarchy of interests‟ to explore new types of interests. The study revealed that „value‟ was the fundamental source of conflict and demonstrated that a coalition which operated predominantly in the informal processes, enhanced the staff‟s power position, building up a „network of power‟ which interlaced between authority and influence to change the decision of those in authority. The process of bargaining enabled actors to resolve their conflict whilst submerging the underlying value controversies once again. Originality/value - The study refines the „toolkit‟ which can be used to analyse how educational institutions manage complex changes. It fills the gap in the knowledge base of micro-political analysis in the higher education sector in Hong Kong and has implications for theory, practice and research.

Non-HLA gene polymorphisms contribute to the immune response, leading to complications of haematopoietic stem cell transplantation (HSCT). A systematic approach using 4,321 microsatellite (MS) markers typing for 2,909 immune response genes (‘immunogenome’) on pooled DNA of 922 Japanese donors and recipients of HSCT was used to identify recipient and donor risk loci for graft-versus-host disease (GVHD). Splitting the population into discovery and confirmation cohorts (460/462 pairs), DNA pools were created for a 2-step pooled DNA screening. Fisher’s exact test for 2x2 (each MS allele) and 2xm Chi Square tests were performed, comparing allele frequencies of recipient/donor pools with GVHD grade 0-1 with those of GVHD grade 2-4. The independent, 2-step pooled DNA screening process has effectively reduced false-positive associations. In the final pooled DNA analysis, 17 (recipient) and 31 (donor) MS loci remained associated with risk or protection from GVHD and were further investigated by individual genotyping in the combined cohorts. Ten of these loci were confirmed to have consistent associations with GVHD; of these, two associations remained when applying multiple testing correction and multivariate statistics: D6S0035i (MAPK14, p=0.00035, OR=0.68) and D1S0818i (ELTD1, p=0.000078, OR=1.52). These findings implicate important new immunoregulatory genes with the process of moderate to severe acute GVHD. These data show that genetic susceptibility to GVHD following HSCT is complex and depends on multiple recipient and donor risk loci. Large-scale genomic screening with microsatellites on pooled DNA, here described for the first time in a HSCT population, is a useful method for the systematic evaluation of multigeneic traits.

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With increasingly higher performance requirements and health care costs associated with dental and orthopaedic bone-anchored implants there is a need to improve the osseointegration of Ti implants. Small alterations in nanotopography feature dimensions and arrangement has recently been shown able to differentiate human mesenchymal stem cells into an osteoblastic lineage, thus showing potential for using nanotopography to improve osseointegration of Ti implants.

Adhesions following abdominal surgery remain a significant unresolved clinical problem causing a great deal of post-operative morbidity. To date adhesion prevention strategies have proven of limited effectiveness. Osteopontin COPN) is a cytokine up-regulated in cell injury and tissue repair. Previous studies have shown that blocking OPN expression in the cutaneous wound demonstrates reduced granulation tissue and scarring without compromising healing. I hypothesise that it might be possible to produce a similar effect on inflammation associated fibrosis that leads to inter-loop bowel adhesions after intra-peritoneal surgery using a murine model. My experimental work on OPN suppression using mRNA blockade by delivering OPN antisense oligodeoxynucleotides on to the surface of injured juxtaposed small bowel supports this hypothesis. There was a significant reduction in granulation tissue and subsequent adhesion size. Also demonstrated was a significant reduction of leukocyte flux, alpha smooth muscle actin expression and collagen density within developing adhesions. There was no impact on mortality or delay in wound healing. Inflammation triggered by expression of OPN was not essential for healing of serosal injury to bowel within the peritoneal cavity. Blocking OPN expression is a very interesting target for anti-adhesion therapeutics.