Macquarie University

About: Macquarie University is a education organization based out in Sydney, New South Wales, Australia. It is known for research contribution in the topics: Population & Context (language use). The organization has 14075 authors who have published 47673 publications receiving 1416184 citations. The organization is also known as: Macquarie uni.

Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma.

Abstract: // Elin S. Gray 1 , Helen Rizos 2,8 , Anna L. Reid 1 , Suzanah C. Boyd 2,8 , Michelle R. Pereira 1 , Johnny Lo 3 , Varsha Tembe 4 , James Freeman 1 , Jenny H.J. Lee 4,5 , Richard A. Scolyer 6,8 , Kelvin Siew 9 , Chris Lomma 9 , Adam Cooper 5 , Muhammad A. Khattak 10,11 , Tarek M. Meniawy 9,11 , Georgina V. Long 7,8 , Matteo S. Carlino 5,8 , Michael Millward 9,11 and Melanie Ziman 1,12 1 School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia 2 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia 3 School of Engineering, Edith Cowan University, Joondalup, Western Australia, Australia 4 Centre for Cancer Research, The University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales, Australia 5 Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, New South Wales, Australia 6 Disciplines of Pathology, The University of Sydney, Sydney, New South Wales, Australia 7 Medicine, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia 8 Melanoma Institute Australia, Sydney, New South Wales, Australia 9 Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia 10 Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia 11 School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia 12 School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Western Australia, Australia Correspondence to: Elin Gray, email: // Keywords : melanoma, ctDNA, acquired resistance, MAPK inhibition, immunotherapy Received : August 03, 2015 Accepted : August 31, 2015 Published : September 22, 2015 Abstract Repeat tumor biopsies to study genomic changes during therapy are difficult, invasive and data are confounded by tumoral heterogeneity. The analysis of circulating tumor DNA (ctDNA) can provide a non-invasive approach to assess prognosis and the genetic evolution of tumors in response to therapy. Mutation-specific droplet digital PCR was used to measure plasma concentrations of oncogenic BRAF and NRAS variants in 48 patients with advanced metastatic melanoma prior to treatment with targeted therapies (vemurafenib, dabrafenib or dabrafenib/trametinib combination) or immunotherapies (ipilimumab, nivolumab or pembrolizumab). Baseline ctDNA levels were evaluated relative to treatment response and progression-free survival (PFS). Tumor-associated ctDNA was detected in the plasma of 35/48 (73%) patients prior to treatment and lower ctDNA levels at this time point were significantly associated with response to treatment and prolonged PFS, irrespective of therapy type. Levels of ctDNA decreased significantly in patients treated with MAPK inhibitors ( p < 0.001) in accordance with response to therapy, but this was not apparent in patients receiving immunotherapies. We show that circulating NRAS mutations, known to confer resistance to BRAF inhibitors, were detected in 3 of 7 (43%) patients progressing on kinase inhibitor therapy. Significantly, ctDNA rebound and circulating mutant NRAS preceded radiological detection of progressive disease. Our data demonstrate that ctDNA is a useful biomarker of response to kinase inhibitor therapy and can be used to monitor tumor evolution and detect the early appearance of resistance effectors.

Evidence for low sulphate and anoxia in a mid-Proterozoic marine basin

Abstract: Many independent lines of evidence document a large increase in the Earth's surface oxidation state 2,400 to 2,200 million years ago1,2,3,4, and a second biospheric oxygenation 800 to 580 million years ago, just before large animals appear in the fossil record5,6. Such a two-staged oxidation implies a unique ocean chemistry for much of the Proterozoic eon, which would have been neither completely anoxic and iron-rich as hypothesized for Archaean seas, nor fully oxic as supposed for most of the Phanerozoic eon7. The redox chemistry of Proterozoic oceans has important implications for evolution8, but empirical constraints on competing environmental models are scarce. Here we present an analysis of the iron chemistry of shales deposited in the marine Roper Basin, Australia, between about 1,500 and 1,400 million years ago, which record deep-water anoxia beneath oxidized surface water. The sulphur isotopic compositions of pyrites in the shales show strong variations along a palaeodepth gradient, indicating low sulphate concentrations in mid-Proterozoic oceans. Our data help to integrate a growing body of evidence favouring a long-lived intermediate state of the oceans, generated by the early Proterozoic oxygen revolution and terminated by the environmental transformation late in the Proterozoic eon.

Canonical form of master equations and characterization of non-Markovianity

Abstract: Master equations govern the time evolution of a quantum system interacting with an environment, and may be written in a variety of forms. Time-independent or memoryless master equations, in particular, can be cast in the well-known Lindblad form. Any time-local master equation, Markovian or non-Markovian, may in fact also be written in a Lindblad-like form. A diagonalization procedure results in a unique, and in this sense canonical, representation of the equation, which may be used to fully characterize the non-Markovianity of the time evolution. Recently, several different measures of non-Markovianity have been presented which reflect, to varying degrees, the appearance of negative decoherence rates in the Lindblad-like form of the master equation. We therefore propose using the negative decoherence rates themselves, as they appear in the canonical form of the master equation, to completely characterize non-Markovianity. The advantages of this are especially apparent when more than one decoherence channel is present. We show that a measure proposed by Rivas et al. [Phys. Rev. Lett. 105, 050403 (2010)] is a surprisingly simple function of the canonical decoherence rates, and give an example of a master equation that is non-Markovian for all times $tg0$, but to which nearly all proposed measures are blind. We also give necessary and sufficient conditions for trace distance and volume measures to witness non-Markovianity, in terms of the Bloch damping matrix.

Subspace methods for large inverse problems with multiple parameter classes

Abstract: SUMMARY Most nonlinear inverse problems can be cast into the form of determining the minimum of a misfit functional of model parameters. This functional determines the misfit between observations and the corresponding theoretical predictions, subject to some regularization conditions on the form of the model. When there is only one type of parameter in the model, methods based on gradient techniques work well, especially when information on rate of change of gradients is included. In the case of problems depending on multiparameter classes, simple gradient methods mix parameters of different character and physical dimensionality. This may lead to rather poor convergence and strong dependence on the scaling of the different parameter types. These difficulties can be overcome by replacing a gradient step by a local minimization in a subspace spanned by a limited number of vectors in model space. The basis vectors for the subspace should be chosen in the directions determined by the variation of the misfit functional with respect to each of the parameter types, with supplementation if required by additional vectors representing the rate of change of the gradient partitions. The construction of the perturbation requires the inversion of a matrix with the dimensions of the subspace which is easily accomplished. Such a subspace scheme takes into account the different functional dependences on the various parameter types in a balanced way. The update to the current model does not depend on the scaling of the individual parameter classes. The subspace method is flexible and can be adapted to a wide range of choices of misfit criterion and modes of representation of the parameter classes. This style of iterative subspace procedure is well adapted to nonlinear problems with dependence on many parameters and can be successfully applied in a variety of problems, e.g. seismic reflection tomography, the simultaneous nonlinear determination of earthquake locations and velocity fields and in the inversion of full seismic waveforms.

Call for a Paradigm Shift in the Genetic Management of Fragmented Populations

Abstract: Thousands of small populations are at increased risk of extinction because genetics and evolutionary biology are not well-integrated into conservation planning–a major lost opportunity for effective actions. We propose that if the risk of outbreeding depression is low, the default should be to evaluate restoration of gene flow to small inbred populations of diploid outbreeding organisms that were isolated by human activities within the last 500 years, rather than inaction. We outline the elements of a scientific-based genetic management policy for fragmented populations of plants and animals, and discuss the reasons why the current default policy is, inappropriately, inaction.