Short-term effects of deep ploughing on soil C stocks following renewal of a dairy pasture in New Zealand

In New Zealand’s high producing permanent pastures the topsoil constitutes a large reservoir of soil organic carbon (SOC), which shows a marked stratification with depth. As consequence, sub-surface layers can contain 10 times less carbon than the surface soil. In permanent pastures with high carbon inputs, the formation and decomposition of these surface SOC stocks are often at equilibrium and C storage shows little change over time. Pastoral based dairy systems utilising ryegrass plus clover cultivars require renewal every 7-10 years to avoid reversion to less productive grasses. This may involve spring cultivation (either no-till, shallow till or full cultivation), summer forage cropping and autumn re-grassing. It has been hypothesised that SOC stocks can be increased by inverting the soil profile at pasture renewal through infrequent (once in 25-30 years) deep mouldboard ploughing (up to 30 cm depth). Increased C sequestration occurs when the new grass quickly rebuilds SOC stocks in the new topsoil (exposed low C sub-soil) at a rate faster than the decomposition of SOC in the rich former topsoil transferred to depth (now below 15 cm). However, benefits form accelerated C storage may be offset if crop and pasture production is adversely affected by the ploughing event (e.g., as result of compaction or excessive drainage). Hence, the aim of this work was to assess the short-term effects of infrequent inversion tillage of long-term New Zealand pastoral-based dairy soils under summer crop management and autumn re-grassing. An imperfectly drained Typic Fragiaqualf under dairy grazing was deep ploughed (approx. 25 cm) and re-sown with turnip in October 2016; other treatments included were shallow (< 10 cm) cultivation and no-till. The site was core sampled (0-40 cm) before cultivation and after 5 months of turnip growth to assess changes in SOC. Plant growth, herbage quality, and nutrient leaching were monitored during the 5-month period; root growth was assessed at the end of the crop rotation. Full cultivation transferred SOC below 10 cm depth, as expected. Soil bulk density decreased whereas root mass increased (10-20 cm depth; P < 0.05) under deep cultivation only. Besides, losses of mineral N were attenuated under deep tillage, resulting in a relative increase in crop yield. The potential for infrequent inversion tillage increasing soil C sequestration as a greenhouse gas (GHG) mitigation tool is currently being tested at other sites in New Zealand

Malarial Retinopathy in Bangladeshi Adults

To establish if assessment of malarial retinopathy in adult malaria using ophthalmoscopy by non-ophthalmologists has clinical and prognostic significance, 210 Bangladeshi adults were assessed by both direct and indirect ophthalmoscopy; 20 of 20 healthy subjects and 20 of 20 patients with vivax malaria showed no retinal changes, whereas in patients with falciparum malaria, indirect ophthalmoscopy revealed malarial retinopathy (predominantly retinal hemorrhages) in 18 of 21 (86%) fatal, 31 of 75 (41%) cerebral, 16 of 64 (25%) non-cerebral but severe, and 1 of 31 (3%) uncomplicated cases. Direct ophthalmoscopy missed retinopathy in one of these cases and found fewer retinal hemorrhages (mean difference = 3.09; 95% confidence interval = 1.50–4.68; P < 0.0001). Severity of retinopathy increased with severity of disease (P for trend < 0.0001), and renal failure, acidosis, and moderate/severe retinopathy were independent predictors of mortality by both ophthalmoscopic techniques. Direct ophthalmoscopy by non-ophthalmologists is an important clinical tool to aid diagnosis and prognosis in adults with severe malaria, and indirect ophthalmoscopy by non-ophthalmologists, although more sensitive, provides minimal additional prognostic information

A phase 1b study of Selumetinib in combination with Cisplatin and Gemcitabine in advanced or metastatic biliary tract cancer: the ABC-04 study

BACKGROUND: Combined treatment with cisplatin and gemcitabine (CisGem) is the standard of care for patients with advanced biliary tract cancer (ABC). Selumetinib (AZD6244, ARRY-142886) potently and selectively inhibits MEK1/2, an intracellular kinase and has shown activity in ABC. The objective of the ABC-04 trial was to establish the recommended dose of selumetinib in combination with CisGem in patients with ABC. METHODS: Eligible patients were ≥ 18 years, had histologically or cytologically-confirmed unresectable recurrent or metastatic biliary tract, gallbladder or ampullary carcinoma, WHO performance status 0-2, and adequate major organ function. Patients may have had prior surgery, radiotherapy or adjuvant chemotherapy, but no prior CisGem and no prior chemotherapy for locally advanced or metastatic disease. Patients received cisplatin 25 mg/m(2) plus gemcitabine 1000 mg/m(2) intravenously on days 1 and 8 of a 21-day cycle. Selumetinib capsules were taken daily. Patients received up to 8 cycles of CisGem and could receive selumetinib until disease progression. A dose de-escalation scheme was used to determine the recommended dose of selumetinib. The first dose level was 75 mg bd. Patients were recruited in cohorts of 3 and assessed for dose limiting toxicity (DLT) during the first cycle of treatment. RESULTS: Thirteen patients were recruited, of whom 12 were evaluable for DLT (1 did not start treatment). All evaluable patients received the starting dose of selumetinib 75 mg bd and one patient experienced a DLT (cardiac chest pain). The median number of days selumetinib was taken (adjusted for the number of days of dose interruptions) was 171.5 (IQR: 75.5 to 344). Two patients remained on treatment at 14 and 19 months post registration. There were 3 temporary and 1 permanent interruptions of selumetinib in cycle 1. Eight patients were evaluable for objective response (RECIST v1.1): 3 had a partial response and 5 stable disease. The median PFS was 6.4 months (IQR 5.2 to 13.7). Toxicities related to selumetinib were mostly related to oedema and rash, grade 1-2 and manageable. Pharmacokinetic analysis showed that the AUC(0-t), AUC(0-∞) and Cmax of selumetinib increased by 12, 11 and 30 % respectively when it was administered with CisGem, while Cmax for the N-desmethyl metabolite of selumetinib decreased by 40 %. There was no evidence that the time of Cmax for selumetinib or N-desmethyl metabolite of selumetinib were different when selumetinib was administered alone or with CisGem. CONCLUSION: The recommended dose of selumetinib when combined with CisGem was 75 mg bd. Translational studies are underway to identify biomarkers that may predict outcome (ClinicalTrials.gov identifier: NCT01242605 July 6(th) 2010)