The aromatase inhibitor letrozole enhances the effect of doxorubicin and docetaxel in an MCF7 cell line model

Introduction: Post-menopausal women with estrogen receptor (ER) positive breast cancer receive adjuvant chemotherapy and endocrine therapy sequentially since tamoxifen may antagonise the cytotoxicity of chemotherapy drugs. With increased use of aromatase inhibitors (AIs) in place of tamoxifen, the potential use of concomitant chemo-endocrine treatments with the AI letrozole, before clinical trials are undertaken, requires evaluation. Methods: MCF7-aro cells expressing the aromatase gene were treated with letrozole, doxorubicin and docetaxel. The effects of different drug concentrations, drug combinations and scheduling on cytotoxicity and aromatase activity were investigated. Key receptor, cell cycle regulation and apoptosis proteins were examined by immunoblotting. Results: Administration of letrozole with either doxorubicin or docetaxel resulted in increased levels of cytotoxicity under all treatment schedules (add in, sequential or simultaneous drug administration) with the greatest anti-proliferative effect observed using concomitant treatment (letrozole first with chemotherapy added in). The inhibitory effect of letrozole on aromatase activity was unchanged by the addition of doxorubicin or docetaxel. Letrozole treatment resulted in decreased HER2 expression and addition of doxorubicin and docetaxel to letrozole led to elevated ER-ß levels. Conclusions: In vitro, letrozole, unlike tamoxifen, enhances the cytotoxicity of both doxorubicin and docetaxel. This supports the prospect of trials using letrozole with chemotherapy in postmenopausal women with ER positive breast cancer

The Virtual Seismologist in SeisComP3: A New Implementation Strategy for Earthquake Early Warning Algorithms

The feasibility of earthquake early warning (EEW) is now widely recognized. However, EEW systems that are in operation or under evaluation worldwide have significant variations and are usually operated independently of routine earthquake monitoring. We introduce a software that allows testing and evaluation of a well‐known EEW algorithm directly within a widely used earthquake monitoring software platform. In the long term, we envision this approach can lead to (1) an easier transition from prototype to production type EEW implementations, (2) a natural and seamless evolution from very fast EEW source parameter estimates with typically large uncertainties to more delayed but more precise estimates using more traditional analysis methods, and (3) the capability of seismic networks to evaluate the readiness of their network for EEW, and to implement EEW, without having to invest in and maintain separate, independent software systems. Using the Virtual Seismologist (VS), a popular EEW algorithm that has been tested in real time in California since 2008, we demonstrate how our approach can be realized within the widely used monitoring platform SeisComP3. Because this software suite is already in production at many seismic networks worldwide, we have been able to test the new VS implementation across a wide variety of tectonic settings and network infrastructures. Using mainly real‐time performance, we analyze over 3200 events with magnitudes between 2.0 and 6.8 and show that, for shallow crustal seismicity, 68% of the first VS magnitude estimates are within ±0.5 magnitude units of the final reported magnitude. We further demonstrate the very significant effect of data communication strategies on final alert times. Using a Monte Carlo simulation approach, we then model the best possible alert times for optimally configured EEW systems and show that, for events within the dense parts of each of the seven test networks, effective warnings could be issued for magnitudes as small as M 5.0

Creatinine- versus cystatin C-based renal function assessment in the Northern Manhattan Study

Background Accurate glomerular filtration rate estimation informs drug dosing and risk stratification. Body composition heterogeneity influences creatinine production and the precision of creatinine-based estimated glomerular filtration rate (eGFRcr) in the elderly. We compared chronic kidney disease (CKD) categorization using eGFRcr and cystatin C-based estimated GFR (eGFRcys) in an elderly, racially/ethnically diverse cohort to determine their concordance. Methods The Northern Manhattan Study (NOMAS) is a predominantly elderly, multi-ethnic cohort with a primary aim to study cardiovascular disease epidemiology. We included participants with concurrently measured creatinine and cystatin C. eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equation. Logistic regression was used to estimate odds ratios and 95% confidence intervals of factors associated with reclassification from eGFRcr≥60ml/min/1.73m2 to eGFRcys<60ml/min/1.73m2. Results Participants (n = 2988, mean age 69±10yrs) were predominantly Hispanic, female, and overweight/obese. eGFRcys was lower than eGFRcr by mean 23mL/min/1.73m2. 51% of participants’ CKD status was discordant, and only 28% maintained the same CKD stage by both measures. Most participants (78%) had eGFRcr≥60mL/min/1.73m2; among these, 64% had eGFRcys65 years, obesity, current smoking, white race, and female sex. Conclusions In a large, multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr. Determining the optimal method to estimate GFR in elderly populations needs urgent further study to improve risk stratification and drug dosing

Automated Additive Construction (AAC) for Earth and Space Using In-situ Resources

Using Automated Additive Construction (AAC), low-fidelity large-scale compressive structures can be produced out of a wide variety of materials found in the environment. Compressionintensive structures need not utilize materials that have tight specifications for internal force management, meaning that the production of the building materials do not require costly methods for their preparation. Where a certain degree of surface roughness can be tolerated, lower-fidelity numerical control of deposited materials can provide a low-cost means for automating building processes, which can be utilized in remote or extreme environments on Earth or in Space. For space missions where every kilogram of mass must be lifted out of Earth’s gravity well, the promise of using in-situ materials for the construction of outposts, facilities, and installations could prove to be enabling if significant reduction of payload mass can be achieved. In a 2015 workshop sponsored by the Keck nstitute for Space Studies, on the topic of Three Dimensional (3D) Additive Construction For Space Using In-situ Resources, was conducted with additive construction experts from around the globe in attendance. The workshop explored disparate efforts, methods, and technologies and established a proposed framework for the field of Additive Construction Using In-situ Resources. This paper defines the field of Automated Additive Construction Using In-situ Resources, describes the state-of-the-art for various methods, establishes a vision for future efforts, identifies gaps in current technologies, explores investment opportunities, and proposes potential technology demonstration missions for terrestrial, International Space Station (ISS), lunar, deep space zero-gravity, and Mars environments

Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis

Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M (IgM). The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. The strategic location of these cells, coupled with the capacity to produce GM-CSF–dependent IgM, ensures effective early frontline defense against bacteria invading the lungs. The study describes a previously unrecognized GM-CSF-IgM axis and positions IRA B cells as orchestrators of protective IgM immunity

Lack of group X secreted phospholipase A₂ increases survival following pandemic H1N1 influenza infection

The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX−/−) model and found that survival after infection was significantly greater in GX−/− mice than in GX+/+ mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX−/− mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX−/− mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza

Revisiting Egyptian Foreign Policy towards Israel under Mubarak: From Cold Peace to Strategic Peace

This article is the first academic study of Egyptian foreign policy towards Israel under Hosni Mubarak (1981–2011). It challenges a deeply entrenched conventional wisdom that Egypt pursued a cold-peace foreign policy towards Israel throughout this period. We demonstrate that Egyptian foreign policy towards Israel was dynamic – comprising cold peace (1981–91), a hybrid foreign policy of cold peace and strategic peace (1991–2003), and a pure strategic peace posture (2003–11). We also use the case of Egyptian foreign policy towards Israel as a heuristic to develop a conception of a new type of peace, strategic peace, as an intermediary analytical category between cold and stable peace

Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma.

INTRODUCTION: Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left. METHODS AND ANALYSIS: The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery-(extended) pleurectomy decortication-versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment. ETHICS AND DISSEMINATION: Research ethics approval was granted by London - Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ISRCTN-ISRCTN44351742 and ClinicalTrials.gov-NCT02040272

Crop Updates 2008 - Farming Systems

This session covers thirty nine papers from different authors: PLENARY 1. Developments in grain end use, Dr John de Majnik, New Grain Products, GRDC, Mr Paul Meibusch, New Farm Products and Services, GRDC, Mr Vince Logan, New Products Executive Manager, GRDC PRESENTATIONS 2. Global warming potential of wheat production in Western Australia: A life cycle assessment, Louise Barton1, Wahid Biswas2 and Daniel Carter3, 1School of Earth & Geographical Sciences, The University of Western Australia, 2Centre of Excellence in Cleaner Production, Division of Science and Engineering, Curtin University of Technology, 3Department of Agriculture and Food 3. How much fuel does your farm use for different farm operations? Nicolyn Short1, Jodie Bowling1, Glen Riethmuller1, James Fisher2 and Moin Salam1, 1Department of Agriculture and Food, 2Muresk Institute, Curtin University of Technology 4. Poor soil water storage and soil constraints are common in WA cropping soils, Stephen Davies, Jim Dixon, Dennis Van Gool and Alison Slade, Department of Agriculture and Food, Bob Gilkes, School of Earth and Geographical Sciences, University of Western Australia 5. Developing potential adaptations to climate change for low rainfall farming system using economic analysis tool. STEP, Megan Abrahams, Caroline Peek, Dennis Van Gool, Daniel Gardiner and Kari-Lee Falconer, Department of Agriculture and Food 6. What soil limitations affect the profitability of claying on non-wetting sandplain soils? David Hall1, Jeremy Lemon1, Harvey Jones1, Yvette Oliver2 and Tania Butler1, 1Department of Agriculture and Food, 2CSIRO Div Sustainable Ecology, Perth 7. Farming systems adapting to a variable climate; Two case studies, Kari-Lee Falconer, Department of Agriculture and Food 8. Importance of accounting for variation in crop yield potential when making fertiliser decisions, Michael Robertson and Yvette Oliver, CSIRO Sustainable Ecosystems, Floreat 9. Soil acidity is a widespread problem across the Avon River Basin, Stephen Carr1, Chris Gazey2, David York1 and Joel Andrew1, 1Precision SoilTech, 2Department of Agriculture and Food 10. The use of soil testing kits and ion-selective electrodes for the analysis of plant available nutrients in Western Australian soils, Michael Simeoni and Bob Gilkes School of Earth and Geographical Sciences, University of Western Australia 11. Redlegged earth mite resistance and integrated strategies for their control in Western Australia, Mangano G. Peter and Micic Svetlana, Department of Agriculture and Food 12. The economics of treating soil pH (liming), Chris Gazey, Steve Davies, Dave Gartner and Adam Clune, Department of Agriculture and Food, 13. Health benefits – A future differentiator for high value grains, Matthew Morell, Theme Leader, CSIRO Food Futures Flagship 14. Carbon in Sustralian cropping soils – We need to be realistic, Alan Umbers (M Rur Sc), GRDC/DAFF Sustainable Industries Initiative Project 15. AGWEST® Bartolo bladder clover (Trifolium spumosum) − a low cost annual pasture legume for the wheat/sheep zone, Angelo Loi, Brad Nutt and Clinton Revell, Department of Agriculture and Food 16. Maximising the value of point based soil sampling: Monitering trends in soil pH through time, Joel Andrew1, David York1, Stephen Carr1 and Chris Gazey2, 1Precision SoilTech, 2Department of Agriculture and Food 17. Improved crop root growth and productivity with deep ripping and deep placed lime, Stephen Davies1, Geoff Kew2*, Chris Gazey1, David Gartner1 and Adam Clune1, 1Department of Agriculture and Food, 2School of Earth and Geographical Sciences University of Western Australia, *Presenting author 18. The role of pastures in hosting Root Lesion Nematode (RLN, Pratylenchus neglectus), Vivien Vanstone, Ali Bhatti and Ming Pei You, Department of Agriculture and Food 19. To rip or not to rip. When does it pay? Imma Farre, Bill Bowden and Stephen Davies, Department of Agriculture and Food 20. Can yield be predicted from remotely sensed data, Henry Smolinski, Jane Speijers and John Bruce, Department of Agriculture and Food 21. Rotations for profit, David McCarthy and Gary Lang, Facey Group, Wickepin, WA 22. Rewriting rules for the new cropping economics, David Rees, Consultant, Albany 23. Reducing business risk in Binnu! – A case study, Rob Grima, Department of Agriculture and Food 24. Does improved ewe management offer grain farmers much extra profit? John Young, Farming Systems Analysis Service, Ross Kingwell, Department of Agriculture and Food, and UWA, Chris Oldham, Department of Agriculture and Food RESEARCH HIGHLIGHTS 25. Crop establishment and productivity with improved root zone drainage, Dr Derk Bakker, Research Officer, Department of Agriculture and Food 26. Will wheat production in Western Australia be more risky in the future? Imma Farre and Ian Foster, Department of Agriculture and Food PAPERS 27. Building farmers’ adaptive capacity to manage seasonal variability and climate change, David Beard, Department of Agriculture and Food 28. Precision placement increases crop phosphorus uptake under variable rainfall: Simulation studies, Wen Chen1 2, Richard Bell1, Bill Bowden2, Ross Brennan2, Art Diggle2 and Reg Lunt2, 1School of Environmental Science, Murdoch University, 2Department of Agriculture and Food 29. What is the role of grain legumes on red soil farms? Rob Grima, Department of Agriculture and Food 30. Fertiliser placement influences plant growth and seed yield of grain crops at different locations of WA, Qifu Ma1, Zed Rengel1, Bill Bowden2, Ross Brennan2, Reg Lunt2 and Tim Hilder2, 1Soil Science & Plant Nutrition, University of Western Australia, 2Department of Agriculture and Food 31. A review of pest and disease occurrences for 2007, Peter Mangano and Dusty Severtson, Department of Agriculture and Food 32. Effect of stocking rates on grain yield and quality of wheat in Western Australia in 2007, Shahajahan Miyan, Sam Clune, Barb Sage and Tenielle Martin, Department of Agriculture and Food 33. Storing grain is not ‘set and forget’ management, Chris Newman, Department of Agriculture and Food 34. Improving understanding of soil plant available water capacity (PAWC): The WA soil water database (APSoil), Yvette Oliver, Neal Dalgliesh and Michael Robertson, CSIRO Sustainable Ecosystems 35. The impact of management decisions in drought on a low rainfall northern wheatbelt farm, Caroline Peek and Andrew Blake, Department of Agriculture and Food 37. Cullen – A native pasture legume shows promise for the low-medium rainfall cropping zone, Megan Ryan, Richard Bennett, Tim Colmer, Daniel Real, Jiayin Pang, Lori Kroiss, Dion Nicol and Tammy Edmonds-Tibbett, School of Plant Biology, The University of Western Australia and Future Farm Industries CRC 38. Climate risk management tools – useful, or just another gadget? Lisa Sherriff, Kari-Lee Falconer, Daniel Gardiner and Ron McTaggart Department of Agriculture and Food 39. Benefits of crop rotation for management of Root Lesion Nematode (RLN, Pratylenchus neglectus), Vivien Vanstone, Sean Kelly and Helen Hunter, Department of Agriculture and Foo