There is evidence that infaunal bivalves in New Zealand are not as abundant as they once were with overfishing and habitat modification contributing to the decline in density and health of cockles. The population biology and abundance of the bivalve Austrovenus stutchburyi (tuangi) in eight beds in four estuaries was assessed both seasonally (13 seasons) and annually (7 years) as little is known about the cockle beds in the Canterbury region of New Zealand. As with populations of similar species worldwide, there were site specific differences in population structure (density and size ranges) with the highest densities at Takamatua (>1500/m²), and the lowest at Port Levy (<350/m²). Gonad indices varied between male and female cockles. Male reproductive cycles were similar at all sites with male cockles being reproductively active year round, while females were more active in spring and summer. Temporal and spatial site specific differences occurred in cockle condition with high salinity sites having higher condition indices (CI) than low salinity sites. There were spatial and temporal variations in salinity (3-35ppt), sediment structure (fine sand through to predominantly silt), water temperature (6-20°C), nutrient supply (total volatile solids (TVS) 0.002- 0.15mg/L) and contaminant levels. Metal pollution indices (MPI) ranged between 3 and 11. Three cockle transplant trials were undertaken both within and between estuarine systems. Caged cockles survived well, and cage design needed to allow vertical movement of the bivalves within the substrate to reduce mortality. At the end of the 12 month trial, approximately 45% of the cockles remained in the plots. The condition of transplanted cockles was similar to naturally occurring cockles. Recommendations are made to optimise the success of cockle transplants. Large scale, un-caged placement of 25-30mm length cockles in the mid-low tide region of areas with stable, but not necessarily uncontaminated substrate, moderate salinity and temperature and with a reliable nutrient supply is recommended. The results from the thesis research can be applied to other infaunal bivalves in New Zealand allowing more successful restoration processes leading to increased species diversity and ecosystem functioning.

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Class of 2012 Abstract / Specific Aims: The purpose of this study was to evaluate the effectiveness of various post-operative prophylaxis methods in lung transplant patients by comparing the incidence of venous thromboembolism (VTE) before and after the implementation of a standardized hospital order set at the University of Arizona Medical Center (UAMC) in April 2007. Methods: Paper and electronic medical charts were retrospectively reviewed if patients had a lung transplant date between October 31, 2003 – October 31, 2010. A computerized database was used to collect demographic data, length of stay (LOS), comorbid conditions, prophylaxis type (including dose/frequency), and date/type of thromboembolic events in the post-operative period prior to discharge and up to 1-year post- discharge. Main Results: Ninety-two patient charts were included in the study with 35 charts in the pre-order set (“Before”) group and 57 charts in the post- order set (“After”) group. All baseline characteristics were similar between groups except age (mean age difference 8.1 yrs, p=0.003), use of mycophenolate (Before n=24, After n=54; p=0.002), and use of medications that increase risk of VTE (Before n=6, After n=2; p=0.05). The April 2007 protocol significantly increased the number of patients receiving any method of prophylaxis (p<0.0001). However, receiving prophlyaxis did not significantly reduce event rates or readmissions due to VTE. Conclusions: Although implementation of the April 2007 protocol did not significantly reduce VTE event rates and readmissions, VTE prophylaxis should continue to remain a priority. Adherence to the implemented protocol may reduce the number of patients left without effective methods of prophylaxis.

Class of 2012 Abstract / Specific Aims: The primary aim of this study was to determine the incidence of posaconazole and voriconazole concentration monitoring that occurs in transplant patients receiving antifungal prophylaxis therapy. The secondary aim was to determine whether voriconazole and posaconazole serum concentrations were used for dose adjustments. Methods: Patients status post either a liquid or solid organ transplant over the age of 1 year who received invasive fungal infection prophylaxis with either posaconazole or voriconazole between the dates of February 1, 2010 through January 31, 2011 while admitted to academic medical center were included in this descriptive retrospective study. This study has been approved by the Institutional Review Board. Data collected on each subject included demographic information, type of transplant, posaconazole or voriconazole concentrations, and duration and dosage adjustments. Main Results: 54 subjects were identified who received either voriconazole or posaconazole for fungal prophylaxis after transplant. For subjects who were prescribed posaconazole (N = 8), concentration monitoring was performed in 50% of subjects and 0% of posaconazole dose adjustments were based on concentrations. For subjects who were prescribed voriconazole, concentration monitoring and dose adjustments based on voriconazole concentrations were performed in 20% and 78% of subjects respectively. Adverse outcomes associated with the use of antifungal therapy were reported in 0% of the posaconazole therapy group and 17% of the voriconazole therapy group. Conclusions: Both posaconazole and voriconazole concentrations were obtained from patients who were receiving antifungal therapy for invasive fungal infection prophylaxis. Adjustments of prophylactic doses are not well characterized.

In allogeneic stem cell mobilization, peripheral blood stem cell mobilization with filgrastim can be considered standard of care. Poor mobilizers may be at risk for inadequate stem cell collection during apheresis. He we present a successful case of salvage plerixafor use with filgrastim in a haploidentical identical transplant patient.

Class of 2006 Abstract / Objectives: To evaluate the efficacy of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, in reducing all-cause mortality and death due to rejection when administered to thoracic organ transplant patients. Methods: Using the following Medical Subject Heading (MeSH) terms and text words: hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, heart transplantation, and lung transplantation, the following data bases were searched: Cochrane Central Register of Controlled Trials (First Quarter 2006), Cochrane Database of Systematic Reviews (First Quarter 2006), Database of Abstracts and Reviews of Effects (First Quarter 2006), ACP Journal Club (1991to January/February 2006), International Pharmaceutical Abstracts (1970-February 2006), and Medline (1966 to February 2006) for English language reports. Three prospective randomized controlled trials (RCTs) and 3 retrospective observational studies were identified as using statins to reduce mortality and death due to fatal rejection in thoracic organ transplant patients. Results: Using all 6 studies (n= 1770 patients), statins decreased mortality by 77% (OR=0.23; [95% confidence interval 0.16-0.34] Z test, P<0.001). Sub-analysis using only RCT heart transplant data showed that statins decreased mortality by 69% (OR=0.31; [95% confidence interval 0.09-1.07] Z test, P<0.003). Sub-analysis using retrospective heart transplant data showed that statins decreased mortality by 75% (OR=0.25; [95% confidence interval 0.16-0.39] Z test, P<0.001). Retrospective lung transplant results (1 study) showed statins decreased mortality by 90% (OR=0.10; [95% confidence interval 0.03-0.34] Z test, P<0.001). Statins also significantly reduced death due to rejection (OR=0.22; [95% confidence interval 0.13-0.37]). Using all 6 studies (n= 1770 patients), statins decreased death due to rejection by 78%. Conclusions: In patients undergoing thoracic organ transplantation, statins significantly decrease all-cause mortality and death due to rejection. Therefore, statins should be routinely administered to these patients following transplant surgery.

Renal transplantation is the optimum treatment for end-stage renal failure. B cells have been identified in chronic allograft damage (CAD) and are associated with the development of tertiary lymphoid tissue within the human renal allograft. To investigate this pathology we utilized a mouse model of renal transplantation. A mouse model of kidney transplantation was first described in 1973. Although the mouse model is technically difficult it is attractive for several reasons: the mouse genome has been characterized and in many aspects is similar to man and there is a greater diversity of experimental reagents and techniques available for mouse studies than other experimental models. We reviewed the literature on all studies of mouse kidney transplantation to report the donor and recipient strain combinations that have been investigated and the resultant survival and histological outcomes. Some models of kidney transplantation have used the transplanted kidney as a life-supporting organ, however in many studies the recipient mouse’s native kidney has been left in situ. Several different combinations of inbred mouse strains have been reported, with varying degrees of injury, survival, or tolerance due to haplotype differences. Both cellular and humoral rejection processes have been observed. This model has been exceptionally useful as an investigational tool to understand multiple aspects of transplantation including acute rejection, cellular and humoral rejection mechanisms and their treatment. Furthermore this model has been used to investigate disease mechanisms beyond transplant rejection including intrinsic renal disease and infection-associated pathology. We performed renal transplantation in mice to model CAD and identified B cells forming tertiary lymphoid tissue with germinal centres. Intra-allograft B220+ B cells comprised of IgMhigh CD23- marginal zone, IgMlo CD23+ follicular zone and IgMlo CD23- transitional-type B cells similar to spleen, and these compartments had elevated expression of CD86. Depletion of B cells with anti-CD20 was associated with an improvement in CAD but only when administered after transplantation and not before. Isolated intra-allograft B cells were cultured and shown to synthesise multiple cytokines, the most abundant of these being GRO-α (CXCL1), RANTES (CCL5), IL-6 and MCP-1 (CCL2). Tubular loss was associated with T cell mediated injury and interstitial fibrosis, whilst type III collagen deposition driven by F4/80+ macrophages and PDGFR-β+ and transgelin+ fibroblasts, all of which were reduced by B cell depletion. In this report we show that intra-allograft B cells are key mediators of chronic damage to the transplant allograft kidney by cytokine orchestration of T cell, macrophage infiltration and fibroblast activation.