Waikato Regional Council

The reach of dialysis in toxicology is limited by two factors, high toxicant volume of distribution and low dialytic extraction of protein bound toxicants in blood. Therapeutic actions for lipid emulsion as antidote are thought involve a "lipid shuttle", whereby lipid droplets in the circulation "shuttle" lipophilic toxicants with "boarding" in well perfused heart and brain tissue with high toxicant concentrations and "exit" to biologically inert slower equilibrating sites such as muscle or adipose where toxicant concentrations are lower. Such a mechanism raises the conceptual possibility of an extracorporeal "exit" potentially mitigating toxicity through increased drug clearance. In experimental models drug binding nanoparticles in dialysate have been shown to mitigate the problem of blood proteins binding toxicant. We investigated whether the addition of intravenous lipid emulsion would increase extraction of amitriptyline into nanoparticle augmented peritoneal dialysate in rats orally dosed with amitriptyline for 1week. Rats were dosed with amitriptyline in drinking water for a week. On the day of the experiment, anaesthetised rats received either an initial bolus then infusion of lipid emulsion for one hour, or a bolus of saline at the initiation of the experiment equal to the total volume of lipid emulsion given. After a 50min equilibration period, a 10min pH gradient nanoparticle augmented peritoneal dialysis dwell was undertaken. Animals were humanely euthanised at the end of the experiment. Blood was sampled 0, 10, 45 and 60min and peritoneal dialysate was analysed for amitriptyline concentration. There were no significant differences in baseline physiology, initial amitriptyline blood concentration, nor pulse and blood pressure at any time between groups. Time weighted individual subject mean blood amitriptyline concentrations (median (IQR)); control 104 (87-125) nmol/l, lipid 219 (148-357) nmol/L, p = 0.03 and dialysate amitriptyline concentration; control 31(14-52) nmol/L, lipid 105 (62-185) nmol/L, p = 0.03 were greater in animals given intravenous lipid emulsion. These are the first data to our knowledge showing experimental support for the approach of simultaneously decreasing volume of distribution with an intravascular nanoparticle in conjunction with a drug binding particle in dialysate. Further work in this area is warranted.

ABSTRACTAimPlant growth‐promoting bacteria (PGPB) play crucial roles in supporting plant growth and, therefore, in undisturbed ecosystems and agricultural systems. We aimed to understand how these microbial communities change under different land use and environmental conditions. This is an important prerequisite to utilising the positive impact PGPB may have for sustainable food production.Location537 sites across Aotearoa New Zealand.Time Period2013–2018.Major Taxa StudiedPlant growth‐promoting bacteria (PGPB).MethodsWe surveyed the PGPB in indigenous and exotic plantation forests, sheep and beef grasslands, dairy pastures and horticulture sites.ResultsPGPB community alpha‐diversity increased with land use intensity, and the greatest portion of explainable variation in alpha‐diversity was accounted for by soil nutrients, metal concentrations, and unexplained spatial patterns. Variation in PGPB community composition, on the other hand, was highest in the forest and horticulture sites and lowest in the grazed pastures. The variation was best accounted for by shared variation among land use, soil nutrients and soil metal concentrations. The relative abundance of nitrogen‐fixing PGPB taxa decreased with land use intensity, largely driven by a decrease in Rhizobiales. In contrast, taxa in the order Bacillales, known for phosphate and potassium solubilisation, increased in relative abundance. Key environmental variables limiting the distributions of specific PGPB taxa included soil pH, several nutrients and the concentrations of cadmium and zinc.Main ConclusionsOverall, we showed that PGPB show distinct patterns in response to land use and soil environmental variables, and these results contribute towards an understanding of the interplay between how we use our soil, their physicochemical properties and the function of the microbial communities within them. This increased understanding of the distribution of PGPB is crucial for advancing our ability to optimise and take advantage of the benefits these bacteria bring to both natural and agricultural land.

ABSTRACT Expansion of extractive industries to deep-sea environments will lead to increased stresses on seafloor ecosystems. We examined changes in environmental parameters following direct and indirect experimental benthic disturbance using a modified plough on the Chatham Rise (∼450 m water depth), Aotearoa/New Zealand. Measurements included sediment community oxygen consumption (SCOC), nutrient fluxes, macro-infauna community composition, and sediment organic carbon (C) and nitrogen (N) content. We observed an increase in SCOC immediately after the disturbance, alongside a decrease in macro-infauna abundance, biomass, species richness, and diversity, and an increase in sediment C:N. One-year after the disturbance, SCOC and sediment C:N ratios were similar to that of pre-disturbance levels, while macro-infauna abundance and biomass were greater. We observed a shift in the community structure at directly disturbed sites one-year post-disturbance with decreased biomass of Polychaeta and increased biomass of Ophiuroidea. No changes were observed in sediment nutrient fluxes. Our study indicates the Chatham Rise benthic ecosystem was initially negatively affected by the disturbance, but the recovery of many parameters after one-year shows the potential resilience of the ecosystem. Compared to many proposed deep-sea resource extraction sites the Chatham Rise experiences a relatively high-level of anthropogenic and natural disturbance which may explain the relatively rapid recovery. Seafloor resilience to human disturbances and recovery from impacts will depend on local environmental conditions that need to be evaluated by environmental impact assessments. This knowledge will be key to predicting and mitigating disturbance impacts. While the Chatham Rise is relatively well studied many other regions, including those planned for extractive activities, lack the information needed.

ABSTRACT Around 3500 New Zealand women will be diagnosed with breast cancer each year. Of these, 45% will be diagnosed through mammography screening, either through BreastScreen Aotearoa or through the private sector. Those diagnosed through screening have better outcomes and importantly more equitable outcomes for Māori and Pacific women. With the advent of many technological changes, there are opportunities to increase the proportion of women who are diagnosed early through systematic screening and thus improve overall mortality from breast cancer. This article discusses the potential opportunities including widening the screening age and addressing the differences in screening rates for Māori and other ethnicities. The review also discusses potential changes to the screening modality (mammography), the value of grading breast density and the use of personalised screening. Finally, the article addresses the potential uses of Artificial Intelligence in assessing risk of cancer and in improving diagnostic accuracy of mammography.

IntroductionThe safest oxygen levels needed for preterm infant respiratory support at birth are uncertain. We aimed to compare the outcomes of infants up to 286 weeks gestation who had respiratory care initiated at birth with fractional inspired oxygen (FiO2) 0.3 or 0.6, which was adjusted to meet specific oxygen saturations (SpO2).MethodsThis randomised controlled phase III trial was stratified by (1) site, (2) gestation and (3) multiplicity. Infants between 23+0 to 28+6 weeks gestation were randomised to initial respiratory support with FiO2 0.3 or 0.6, adjusted to meet common SpO2 targets for the first 10 min.Primary outcomeSurvival to 36 weeks gestation without documented brain injury.AssessmentsFiO2, SpO2 and heart rate were recorded each minute from delivery for 10 min. Assessments were obtained at baseline, 36 weeks, discharge and at 2 years corrected gestation, along with a parent questionnaire.Statistical analysis planAssuming 32% of infants would die or survive with brain injury by 36 weeks, 735 infants per arm (1470 total) were needed to detect a risk difference of 8% (25% relative risk reduction), with 10% non-adherence to protocol, 85% β and 5% α.EthicsApproved by the John Hunter Human Research Ethics Committee (2019/ETH/3837) for waiver of consent for all Australian sites for randomised allocation and primary outcome.ConclusionRecruitment started in 2018 and was achieved on 30 September 2024. The Data and Safety Committee review found no major safety concerns at 50% recruitment.Trial registration numberACTRN 12618000879268.

Background: Despite the impressive outcomes seen with tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukaemia (CML), the optimal upfront therapy remains unclear. Second generation TKI (2G TKI) trials have shown significantly more rapid and deeper levels of molecular response with a lower incidence of progression to advanced stage disease, but no improvement in overall survival. 2G TKIs are however associated with long term side effects, including increased vascular events in patients receiving nilotinib and pulmonary toxicity in patients on dasatinib. In contrast, the innovator TKI imatinib has now been used in New Zealand for over 20 years, with side effects that are mild and manageable, and no emergent long term toxicity, making it an attractive option for safe, long term therapy. Aims: The objective of the KISS study (Kinase Inhibition with Sprycel Startup) is to investigate the efficacy and safety of de-escalating upfront 2G TKI therapy with dasatinib to imatinib in patients with chronic myeloid leukaemia (CML) who have reached a “safe haven” as defined by achieving MR3.0 after 12 months of therapy. Methods: This is a phase II trial of newly diagnosed adult patients with chronic phase CML (CP-CML) recruited from 9 New Zealand haematology centres, and treated upfront with dasatinib 100mg once daily. Patients achieving a confirmed MR3.0 at 12 months were transitioned to imatinib 400mg once daily and followed for 24 months. The primary objective is the proportion of patients who remain in MR3.0 for 2 years following the change of therapy from dasatinib to imatinib. Results: 96 patients with CP-CML were recruited between 17 July 2017 and 14 April 2022, with data cut off 31 December 2022. Currently 75 patients have at least 12 months of follow up and 10 patients continue on dasatinib but have not yet reached the 12 month assessment. During the first 12 months of the study, 19 patients have withdrawn (n=11, including 2 patients with variant transcripts not able to be monitored by quantitative PCR) or discontinued study treatment (n=8); toxicity was the cause of this in 11 out of 19 patients. To date, 44 of 67 patients have achieved a confirmed MR3.0 after 12 months of dasatinib treatment. Of the 44 patients with confirmed MR3.0 at 12 months, 38 have consented to transition to imatinib. Summary/Conclusion: Preliminary analysis of the KISS study suggests this is a feasible and well tolerated strategy. Longer term follow up, and molecular data will confirm whether this strategy can be used to rapidly induce a molecular response with initial 2G TKI therapy, followed by ongoing therapy with imatinib, avoiding the potential for significant off target side effects. Keywords: Molecular response, Tyrosine kinase inhibitor, Chronic myeloid leukemia, Toxicity

Trauma continues to place a burden on individuals, communities and health care systems around the world. To help reduce this burden and improve care, trauma registries in Australia and Aotearoa New Zealand collect standardized data on patients admitted with Injury Severity Scores greater than 12. There is currently no agreed minimum data set for trauma patients with Injury Severity Score less than 13, representing an opportunity to provide more data for quality improvement and injury prevention. A binational, expert, advisory group assessed the value of potential fields for a minimum dataset for low severity trauma. Existing trauma registries in Australia and Aotearoa New Zealand were assessed to ensure compatibility. Thirty-five data fields met criteria for inclusion in the low-severity minimum dataset. The fields comprised a subset of the Australia New Zealand Major Trauma Registry and were included in existing low-severity registries. A minimum data set for low severity has been defined for use in Australia and Aotearoa New Zealand. In addition to high severity trauma data this will provide a standard for data collection that will contribute to quality improvement and injury prevention.