Unravelling upbuilding pedogenesis in tephra and loess sequences in New Zealand using tephrochronology

The genesis of soils developed in either tephra or loess on stable sites differs markedly from that of soils developed on rock because classical topdown processes operate in conjuction with geological processes whereby material is added to the land surface so that the soils form by upbuilding pedogenesis. Understanding the genesis of such soils (typically Andisols and Alfisols, respectively) often requires a stratigraphic approach combined with an appreciation of buried soil horizons and polygenesis. In New Zealand, calendrically-dated tephras provide an advantage for assessing rates of upbuilding through chronostratigraphy. Many Andisol profiles form by upbuilding pedogenesis as younger tephra materials are deposited on top of older ones. The resultant profile character reflects interplay between the rate at which tephras are added to the land surface and topdown processes that produce andic materials and horizons. In loess terrains, upbuilding pedogenesis since c. 25,000 years ago is associated with maximum rates of loess accumulation c. 3 10 mm per century, sufficiently slow for soil-forming processes to continue to operate as the land surface gradually rises. Thus, Alfisol subsoil features are only weakly developed and Bw or B(x) horizons typically are formed. In contrast, topdown pedogenesis is associated with minimal or zero loess accumulation, the land surface elevation remains essentially constant, and subsoil features become more strongly developed and Bg, Bt, or Bx horizons typically are formed

Characterisation of HLA-specific antibodies

A successful kidney transplant is the best treatment for established renal failure, yet around 300 patients per annum are denied transplants because they have antibodies, most notably directed against donor HLA or ABO in their blood, which have the potential to cause acute and chronic rejection of the transplant. Such antibodies are present in 25% (roughly 1750 of the 7000 on the kidney transplant waiting list) of the patients listed for a deceased donor transplant. Programmes to remove antibody and transplant patients across HLA antibody barriers have been developed, but are limited by a high rate of acute rejection. This thesis explores the factors which may impact upon the pathogenicity of HLA-specific antibodies and also aims to enhance the understanding of the techniques used in the laboratory to define these antibodies. A range of studies were carried out examining factors such as the IgG subclass composition of the anti-HLA response. Assay variations were designed to enable a higher definition of antibody specificity to be achieved, and for the first time in the literature the direct quantification of HLA-specific antibodies in patient sera was performed. In addition, proof of principle design and testing was carried out on a novel prototype therapeutic device for the selective depletion of HLA-specific antibodies directly from patient plasma and sera. The antibodies isolated from this approach were also used in studies to examine the factors which determine serum cytotoxicity

Obituary − Emeritus Professor Dr John Davidson McCraw (1925−2014) MBE, MSc NZ, DSc Well, CRSNZ, FNZSSS.

John McCraw was an Earth scientist who began working as a pedologist with Soil Bureau, DSIR, then became the Foundation Professor of Earth Sciences at the University of Waikato in Hamilton, inspiring a new generation to study and work in Earth sciences . In retirement, John McCraw was an author and historian with a special emphasis on Central Otago as well as the Waikato region. Throughout his career, marked especially by exemplary leadership, accomplished administration, and commitment to his staff and students at the University of Waikato, John McCraw also contributed to the communities in which he lived through public service organizations and as a public speaker. He received a number of awards including an MBE, fellowship, and companionship, and, uniquely, is commemorated also with a glacier, a fossil, and a museum-based research room named for him. Emeritus Professor John McCraw passed away on the 14th of December, 2014. An obituary, entitled “Dedicated to earth science and his students”, was published in the Waikato Times on the 10th of January, 2015

Behaviour of non-donor specific antibodies during rapid re-synthesis of donor specific HLA antibodies after antibody incompatible renal transplantation

Background: HLA directed antibodies play an important role in acute and chronic allograft rejection. During viral infection of a patient with HLA antibodies, the HLA antibody levels may rise even though there is no new immunization with antigen. However it is not known whether the converse occurs, and whether changes on non-donor specific antibodies are associated with any outcomes following HLA antibody incompatible renal transplantation. Methods: 55 patients, 31 women and 24 men, who underwent HLAi renal transplant in our center from September 2005 to September 2010 were included in the studies. We analysed the data using two different approaches, based on; i) DSA levels and ii) rejection episode post transplant. HLA antibody levels were measured during the early post transplant period and corresponding CMV, VZV and Anti-HBs IgG antibody levels and blood group IgG, IgM and IgA antibodies were quantified. Results: Despite a significant DSA antibody rise no significant non-donor specific HLA antibody, viral or blood group antibody rise was found. In rejection episode analyses, multiple logistic regression modelling showed that change in the DSA was significantly associated with rejection (p = 0.002), even when adjusted for other antibody levels. No other antibody levels were predictive of rejection. Increase in DSA from pre treatment to a post transplant peak of 1000 was equivalent to an increased chance of rejection with an odds ratio of 1.47 (1.08, 2.00). Conclusion: In spite of increases or decreases in the DSA levels, there were no changes in the viral or the blood group antibodies in these patients. Thus the DSA rise is specific in contrast to the viral, blood group or third party antibodies post transplantation. Increases in the DSA post transplant in comparison to pre-treatment are strongly associated with occurrence of rejection

A new data-driven model for post-transplant antibody dynamics in high risk kidney transplantation

The dynamics of donor specific human leukocyte antigen (HLA) antibodies during early stage after transplantation are of great clinical interest as they are considered to be associated with short and long term outcomes (graft function and rejection). However, the limited number of such detailed donor-specific antibody (DSA) time series currently available and their diverse patterns have made the task of modelling difficult. Focusing on one typical dynamic pattern with rapid falls and stable settling levels, a novel data-driven model in the form of a third order differential equation has been developed to describe such post-transplant dynamics in DSAs for the first time. A variational Bayesian inference method has been applied to select a model and learn its parameters for 39 time series from two groups of graft recipients, i.e. patients with and without acute antibody-mediated rejection (AMR) episodes. Linear and nonlinear dynamic models of different order were attempted to fit the time series, and the third order linear model provided the best description of the common features in both groups. Both deterministic and stochastic parameters are found to be significantly different in the AMR and no-AMR groups. Eigenvalues have been calculated for each fitting, and phase portraits have been plotted to show the trajectories of the system states for both groups. The results from our previous study with fewer cases have been further confirmed: the time series in the AMR group have significantly higher frequency of oscillations and faster dissipation rates, which may potentially lead to better laboratory measurement strategy and a better chance of understanding the underlying immunological mechanisms

The working life of John McCraw (1925-2014): a remarkable New Zealand pedologist and Earth scientist

John McCraw was an Earth scientist who began working as a pedologist with Soil Bureau, DSIR, then became the Foundation Professor of Earth Sciences at the University of Waikato in Hamilton, inspiring a new generation to study and work in Earth sciences, a discipline he introduced into the tertiary education system in New Zealand. In retirement, he was an author and historian with a special emphasis on Central Otago as well as the Waikato region. Throughout his career, marked especially by meritorious leadership, accomplished administration, and commitment to his staff and students at the University of Waikato, John McCraw also contributed widely to the communities in which he lived through public service organizations and as a public speaker. He received a number of awards including an MBE, fellowship, and companionship, and, uniquely, is commemorated also with a glacier, a fossil, and a museum-based research room named for him. The Earth sciences programme today as an integral part of the School of Science at the University of Waikato is stronger than ever. In the past few years several new staff have been appointed, both academic and technical, giving the largest-ever Earth sciences team of about 30 staff. As well as research-led teaching, Earth sciences has strong research groups, at the cores of which are doctoral and masterate students, and postdoctoral fellows, to carry on the work envisaged by John McCraw all those years ago. This thriving continuation of our discipline, which has always had strong multidisciplinary linkages with other sciences, is − alongside the countless students he has taught and inspired − surely his greatest legacy

Subclass analysis of donor HLA-specific IgG in antibody-incompatible renal transplantation reveals a significant association of IgG4 with rejection and graft failure

Donor HLA-specific antibodies (DSAs) can cause rejection and graft loss after renal transplantation, but their levels measured by the current assays are not fully predictive of outcomes. We investigated whether IgG subclasses of DSA were associated with early rejection and graft failure. DSA levels were determined pretreatment, at the day of peak pan-IgG level and at 30 days post-transplantation in eighty HLA antibody-incompatible kidney transplant recipients using a modified microbead assay. Pretreatment IgG4 levels were predictive of acute antibody-mediated rejection (P = 0.003) in the first 30 days post-transplant. Pre-treatment presence of IgG4 DSA (P = 0.008) and day 30 IgG3 DSA (P = 0.03) was associated with poor graft survival. Multivariate regression analysis showed that in addition to pan-IgG levels, total IgG4 levels were an independent risk factor for early rejection when measured pretreatment, and the presence of pretreatment IgG4 DSA was also an independent risk factor for graft failure. Pretreatment IgG4 DSA levels correlated independently with higher risk of early rejection episodes and medium-term death-censored graft survival. Thus, pretreatment IgG4 DSA may be used as a biomarker to predict and risk stratify cases with higher levels of pan-IgG DSA in HLA antibody-incompatible transplantation. Further investigations are needed to confirm our results

Decision tree and random forest models for outcome prediction in antibody incompatible kidney transplantation

Clinical datasets are commonly limited in size, thus restraining applications of Machine Learning (ML)techniques for predictive modelling in clinical research and organ transplantation. We explored thepotential of Decision Tree (DT) and Random Forest (RF) classification models, in the context of smalldataset of 80 samples, for outcome prediction in high-risk kidney transplantation. The DT and RF modelsidentified the key risk factors associated with acute rejection: the levels of the donor specific IgG anti-bodies, the levels of IgG4 subclass and the number of human leucocyte antigen mismatches betweenthe donor and recipient. Furthermore, the DT model determined dangerous levels of donor-specific IgGsubclass antibodies, thus demonstrating the potential of discovering new properties in the data whentraditional statistical tools are unable to capture them. The DT and RF classifiers developed in this workpredicted early transplant rejection with accuracy of 85%, thus offering an accurate decision supporttool for doctors tasked with predicting outcomes of kidney transplantation in advance of the clinicalintervention

Dynamic behaviour of donor specific antibodies in the early period following HLA incompatible kidney transplantation

In HLA-incompatible kidney transplantation, monitoring donor-specific antibodies (DSA) plays a crucial role in providing appropriate treatment and increases kidney survival times. This work aimed to determine if early post-transplant DSA dynamics inform graft outcome over and above other predictive factors. Eighty-eight cases were classified by unsupervised machine learning into five distinct DSA response groups: no response, fast modulation, slow modulation, rise to sustained and sustained. Fast modulation dynamics gave an 80% rate for early acute rejection, whereas the sustained group was associated with the lowest rejection rates (19%). In complete contrast, the five-year graft failure was lowest in the modulation groups (4–7%) and highest in the sustained groups (25–31%). Multivariable analysis showed that a higher pre-treatment DSA level, male gender and absence of early acute rejection were strongly associated with a sustained DSA response. The modulation group had excellent five-year outcomes despite higher rates of early rejection episodes. This work further develops an understanding of post-transplant DSA dynamics and their influence on graft survival following HLA-incompatible kidney transplantation