Chemical Components and Effects on Soil Quality in Temperate Grazed Pasture Systems

Key points 1. Legume/grass pastures retain feedbacks on N supply that may help to reduce losses of N to the wider environment. 2. Intensive use of N fertilisers tends to increase SOM turnover and increase losses of N to the environment. 3. Increased use of fertilisers has contributed little to soil organic matter storage in grazed pastoral systems

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)

Automated Detection of Malarial Retinopathy in Digital Fundus Images for Improved Diagnosis in Malawian Children with Clinically Defined Cerebral Malaria

Cerebral malaria (CM), a complication of malaria infection, is the cause of the majority of malaria-associated deaths in African children. The standard clinical case definition for CM misclassifies ~25% of patients, but when malarial retinopathy (MR) is added to the clinical case definition, the specificity improves from 61% to 95%. Ocular fundoscopy requires expensive equipment and technical expertise not often available in malaria endemic settings, so we developed an automated software system to analyze retinal color images for MR lesions: retinal whitening, vessel discoloration, and white-centered hemorrhages. The individual lesion detection algorithms were combined using a partial least square classifier to determine the presence or absence of MR. We used a retrospective retinal image dataset of 86 pediatric patients with clinically defined CM (70 with MR and 16 without) to evaluate the algorithm performance. Our goal was to reduce the false positive rate of CM diagnosis, and so the algorithms were tuned at high specificity. This yielded sensitivity/specificity of 95%/100% for the detection of MR overall, and 65%/94% for retinal whitening, 62%/100% for vessel discoloration, and 73%/96% for hemorrhages. This automated system for detecting MR using retinal color images has the potential to improve the accuracy of CM diagnosis

Teachers as leaders in a knowledge society: encouraging signs of a new professionalism

[Abstract]: Challenges confronting schools worldwide are greater than ever,and, likewise, many teachers possess capabilities, talents, and formal credentials more sophisticated than ever. However, the responsibility and authority accorded to teachers have not grown significantly, nor has the image of teaching as a profession advanced significantly. The question becomes, what are the implications for the image and status of the teaching profession as the concept of knowledge society takes a firm hold in the industrialized world? This article addresses the philosophical underpinnings of teacher leadership manifested in case studies where schools sought to achieve the generation of new knowledge as part of a process of whole-school revitalization. Specifically, this article reports on Australian research that has illuminated the work of teacher leaders engaged in the IDEAS project, a joint school revitalization initiative of the University of Southern Queensland and the Queensland Department of Education and the Arts

Spin-orbit coupling controlled ground states in the double perovskite iridates A2BIrO6 (A = Ba, Sr; B = Lu, Sc)

Iridates with the 5$d^4$ electronic configuration have attracted recent interest due to reports of magnetically-ordered ground states despite longstanding expectations that their strong spin-orbit coupling would generate a $J = 0$ electronic ground state for each Ir$^{5+}$ ion. The major focus of prior research has been on the double perovskite iridates Ba$_2$YIrO$_6$ and Sr$_2$YIrO$_6$, where the nature of the ground states (i.e. ordered vs non-magnetic) is still controversial. Here we present neutron powder diffraction, high energy resolution fluorescence detected x-ray absorption spectroscopy (HERFD-XAS), resonant inelastic x-ray scattering (RIXS), magnetic susceptibility, and muon spin relaxation data on the related double perovskite iridates Ba$_2$LuIrO$_6$, Sr$_2$LuIrO$_6$, Ba$_2$ScIrO$_6$, and Sr$_2$ScIrO$_6$ that enable us to gain a general understanding of the electronic and magnetic properties for this family of materials. Our HERFD-XAS and RIXS measurements establish $J = 0$ electronic ground states for the Ir$^{5+}$ ions in all cases, with similar values for Hund's coupling $J_{\rm H}$ and the spin-orbit coupling constant $\lambda_{\rm SOC}$. Our bulk susceptibility and muon spin relaxation data find no evidence for long-range magnetic order or spin freezing, but they do reveal weak magnetic signals that are consistent with extrinsic local moments. Our results indicate that the large $\lambda_{\rm SOC}$ is the key driving force behind the electronic and magnetic ground states realized in the 5$d^4$ double perovskite iridates, which agrees well with conventional wisdom.Comment: 13 pages, 7 figures, accepted for publication by PR

Physics–Dynamics Coupling in weather, climate and Earth system models: Challenges and recent progress

This is the final version. Available from American Meteorological Society via the DOI in this record.Numerical weather, climate, or Earth system models involve the coupling of components. At a broad level, these components can be classified as the resolved fluid dynamics, unresolved fluid dynamical aspects (i.e., those represented by physical parameterizations such as subgrid-scale mixing), and nonfluid dynamical aspects such as radiation and microphysical processes. Typically, each component is developed, at least initially, independently. Once development is mature, the components are coupled to deliver a model of the required complexity. The implementation of the coupling can have a significant impact on the model. As the error associated with each component decreases, the errors introduced by the coupling will eventually dominate. Hence, any improvement in one of the components is unlikely to improve the performance of the overall system. The challenges associated with combining the components to create a coherent model are here termed physics–dynamics coupling. The issue goes beyond the coupling between the parameterizations and the resolved fluid dynamics. This paper highlights recent progress and some of the current challenges. It focuses on three objectives: to illustrate the phenomenology of the coupling problem with references to examples in the literature, to show how the problem can be analyzed, and to create awareness of the issue across the disciplines and specializations. The topics addressed are different ways of advancing full models in time, approaches to understanding the role of the coupling and evaluation of approaches, coupling ocean and atmosphere models, thermodynamic compatibility between model components, and emerging issues such as those that arise as model resolutions increase and/or models use variable resolutions.Natural Environment Research Council (NERC)National Science FoundationDepartment of Energy Office of Biological and Environmental ResearchPacific Northwest National Laboratory (PNNL)DOE Office of Scienc