How integrative modelling can break down disciplinary silos

This paper has been published in a peer-reviewed journal as: Kragt, M.E., Robson, B.J. & Macleod, C.J.A. (2013) Modellers’ roles in structuring integrative research projects. Environmental Modelling & Software, 39(1): 322-330. DOI: 10.1016/j.envsoft.2012.06.015Environmental modelling, Interdisciplinary research, Transdisciplinarity, Integration, Research Methods/ Statistical Methods, Q57, Y80, Z19,

Incorporating a generalised additive model of river nutrient concentrations into a mechanistic receiving water model

eReefs is a large, collaborative project that is building catchment and marine models for Australia's Great Barrier Reef Lagoon (GBRL), a world-heritage environmental asset. The eReefs package includes three-dimensional mechanistic biogeochemical, sediment and hydrodynamic models for the entire GBRL on 4 km and 1 km grid scales, along with a relocatable coastal and estuary model (RECOM) that can be nested within the larger-scale models. Source Catchment models developed by the Government of Queensland for each GBRL catchment will be used to run scenarios to predict the effects of management and land use changes on nitrogen, phosphorus and sediment loads reaching each river. For day-to-day near-real-time and forecast-mode running of the marine models, however, another approach is needed to provide the river loads of sediments, dissolved and particulate loads required as boundary conditions. Generalised Additive Models (GAMs) have been shown (e. g. Kuhnert et al., 2012) to be powerful tools for the prediction of suspended sediment and particulate nutrient loads in tropical rivers. Here, we extend previous work to build GAMs that are able to predict concentrations of suspended sediments, dissolved and particulate nutrients in the Fitzroy River (Queensland) on a daily time-step. In developing the GAMs, we tested a number of routinely and frequently measured meteorological and hydrological variables for potential predictive power. The new terms considered included water temperature (which may alter biogeochemical processing rates), air temperature (a more reliably measured proxy for water temperature), electrical conductivity (which may reflect the influence of particular subcatchment sources), barometric pressure (an indicator of local storm activity), wind stress (which may affect resuspension and mixing in the river and its weirs) and flow from river tributaries (a direct measure of the influence of particular subcatchments). The models generated were tested with regard to the validity of key statistical assumptions, and were then validated against a subset of observational data that had been held back from the original calibration. The strongest models included flow in the Fitzroy River, flow in one or more tributaries, and a discounted flow term that reflected flow in the preceding days and weeks. Models that did not include tributary flow were able to predict concentrations of particulate, but not dissolved materials. Neither meteorological terms nor electrical conductivity proved to be useful predictors, while water temperature was of marginal value. The final GAM provide more accurate predictions on a daily time-step than previously available methods, for both dissolved and particulate materials, and is being used to provide time-series input (e. g. Figure 1) to mechanistic marine models

eReefs modelling suggests Trichodesmium may be a major nitrogen source in the Great Barrier Reef

Trichodesmium can fix nitrogen that is later released into the water column. This process may be a major source of ‘new’ nitrogen in the Great Barrier Reef (GBR), but to date this contribution is poorly resolved. We have estimated the seasonal, spatial and annual contributions of Trichodesmium to the annual nitrogen budget of the GBR using the eReefs marine models. Models were run for the interval December 2010 to November 2012. During this period La Niña conditions produced record rainfalls and widespread flooding of GBR catchments. Model outputs suggest nitrogen fixation by Trichodesmium in the GBR (which covers about 348,000 km2) contributes approximately 0.5 MT/yr, exceeding the total average annual riverine nitrogen loads (0.05–0.08 MT/yr). Nitrogen fixation loads are exceeded by riverine loads only if the comparison is restricted to inshore waters and during the wet season. The river pollution is likely to have impacts in freshwater wetlands, mangroves, seagrasses and in-shore coral reefs; while Trichodesmium blooms are likely to be less intense but more widespread and affect offshore coral reefs and other oceanic ecosystems. Phosphorus and iron are suggested to be potential drivers of Trichodesmium growth and nitrogen fixation. This result is provisional but reinforces the need for more detailed assessment and reliable quantification of the annual nitrogen contribution from nitrogen fixation in the GBR and other coastal waters. Such advances will improve understandings of the role of terrestrial nitrogen loads in the GBR and of terrestrial phosphorus and iron loads which can modulate Trichodesmium abundance. These findings will help to broaden the focus of water quality management programmes and support management to improve GBR water quality

Model for deriving benthic irradiance in the Great Barrier Reef from MODIS satellite imagery

We demonstrate a simple, spectrally resolved ocean color remote sensing model to estimate benthic photosynthetically active radiation (bPAR) for the waters of the Great Barrier Reef (GBR), Australia. For coastal marine environments and coral reefs, the underwater light field is critical to ecosystem health, but data on bPAR rarely exist at ecologically relevant spatio-temporal scales. The bPAR model presented here is based on Lambert-Beer’s Law and uses: (i) sea surface values of the downwelling solar irradiance, Es(λ); (ii) high-resolution seafloor bathymetry data; and (iii) spectral estimates of the diffuse attenuation coefficient, Kd(λ), calculated from GBR-specific spectral inherent optical properties (IOPs). We first derive estimates of instantaneous bPAR. Assuming clear skies, these instantaneous values were then used to obtain daily integrated benthic PAR values. Matchup comparisons between concurrent satellite-derived bPAR and in situ values recorded at four optically varying test sites indicated strong agreement, small bias, and low mean absolute error. Overall, the matchup results suggest that our benthic irradiance model was robust to spatial variation in optical properties, typical of complex shallow coastal waters such as the GBR. We demonstrated the bPAR model for a small test region in the central GBR, with the results revealing strong patterns of temporal variability. The model will provide baseline datasets to assess changes in bPAR and its external drivers and may form the basis for a future GBR water-quality index. This model may also be applicable to other coastal waters for which spectral IOP and high-resolution bathymetry data exist

A spatial analysis of seagrass habitat and community diversity in the Great Barrier Reef World Heritage Area

The Great Barrier Reef World Heritage Area (GBRWHA) in north eastern Australia spans 2,500 km of coastline and covers an area of ~350,000 km2. It includes one of the world’s largest seagrass resources. To provide a foundation to monitor, establish trends and manage the protection of seagrass meadows in the GBRWHA we quantified potential seagrass community extent using six random forest models that include environmental data and seagrass sampling history. We identified 88,331 km2 of potential seagrass habitat in intertidal and subtidal areas: 1,111 km2 in estuaries, 16,276 km2 in coastal areas, and 70,934 km2 in reef areas. Thirty-six seagrass community types were defined by species assemblages within these habitat types using multivariate regression tree models. We show that the structure, location and distribution of the seagrass communities is the result of complex environmental interactions. These environmental conditions include depth, tidal exposure, latitude, current speed, benthic light, proportion of mud in the sediment, water type, water temperature, salinity, and wind speed. Our analysis will underpin spatial planning, can be used in the design of monitoring programs to represent the diversity of seagrass communities and will facilitate our understanding of environmental risk to these habitats

How models can support ecosystem-based management of coral reefs

Despite the importance of coral reef ecosystems to the social and economic welfare of coastal communities, the condition of these marine ecosystems have generally degraded over the past decades. With an increased knowledge of coral reef ecosystem processes and a rise in computer power, dynamic models are useful tools in assessing the synergistic effects of local and global stressors on ecosystem functions. We review representative approaches for dynamically modeling coral reef ecosystems and categorize them as minimal, intermediate and complex models. The categorization was based on the leading principle for model development and their level of realism and process detail. This review aims to improve the knowledge of concurrent approaches in coral reef ecosystem modeling and highlights the importance of choosing an appropriate approach based on the type of question(s) to be answered. We contend that minimal and intermediate models are generally valuable tools to assess the response of key states to main stressors and, hence, contribute to understanding ecological surprises. As has been shown in freshwater resources management, insight into these conceptual relations profoundly influences how natural resource managers perceive their systems and how they manage ecosystem recovery. We argue that adaptive resource management requires integrated thinking and decision support, which demands a diversity of modeling approaches. Integration can be achieved through complimentary use of models or through integrated models that systemically combine all relevant aspects in one model. Such whole-of-system models can be useful tools for quantitatively evaluating scenarios. These models allow an assessment of the interactive effects of multiple stressors on various, potentially conflicting, management objectives. All models simplify reality and, as such, have their weaknesses. While minimal models lack multidimensionality, system models are likely difficult to interpret as they require many efforts to decipher the numerous interactions and feedback loops. Given the breadth of questions to be tackled when dealing with coral reefs, the best practice approach uses multiple model types and thus benefits from the strength of different models types

Hypoxia-induced nitric oxide production and tumour perfusion is inhibited by pegylated arginine deiminase (ADI-PEG20).

The hypoxic tumour microenvironment represents an aggressive, therapy-resistant compartment. As arginine is required for specific hypoxia-induced processes, we hypothesised that arginine-deprivation therapy may be useful in targeting hypoxic cancer cells. We explored the effects of the arginine-degrading agent ADI-PEG20 on hypoxia-inducible factor (HIF) activation, the hypoxia-induced nitric oxide (NO) pathway and proliferation using HCT116 and UMUC3 cells and xenografts. The latter lack argininosuccinate synthetase (ASS1) making them auxotrophic for arginine. In HCT116 cells, ADI-PEG20 inhibited hypoxic-activation of HIF-1α and HIF-2α, leading to decreased inducible-nitric oxide synthase (iNOS), NO-production, and VEGF. Interestingly, combining hypoxia and ADI-PEG20 synergistically inhibited ASS1. ADI-PEG20 inhibited mTORC1 and activated the unfolded protein response providing a mechanism for inhibition of HIF and ASS1. ADI-PEG20 inhibited tumour growth, impaired hypoxia-associated NO-production, and decreased vascular perfusion. Expression of HIF-1α/HIF-2α/iNOS and VEGF were reduced, despite an increased hypoxic tumour fraction. Similar effects were observed in UMUC3 xenografts. In summary, ADI-PEG20 inhibits HIF-activated processes in two tumour models with widely different arginine biology. Thus, ADI-PEG20 may be useful in the clinic to target therapy-resistant hypoxic cells in ASS1-proficient tumours and ASS1-deficient tumours.Thanks to Dr John Bomalaski, (Polaris Pharmaceuticals, Inc) for supplying the ADI-PEG20, to Dr Simon S Hoer for useful discussions and to members of Histopathology/ISH (CRUK Cambridge Institute, UK) for IHC and imaging assistance. This work was supported by the Wellcome Trust and the NIHR Cambridge Biomedical Research Centre Senior Investigator Awards (to P.H.M., supporting N.B.), EU FP7 Metoxia Grant agreement no. 222741 (to P.H.M., supporting G.C.), UCL Cancer Research UK Centre (to M.R.), King’s College London and UCL Comprehensive Cancer Imaging Centre, Cancer Research UK and EPSRC in association with the Medical Research Council (MRC), the DoH (England: to R.B.P.), MRC Cancer Unit Core Funding (to C.F., supporting E.G.).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep2295

Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

The exposure of the Great Barrier Reef to ocean acidification

The Great Barrier Reef (GBR) is founded on reef-building corals. Corals build their exoskeleton with aragonite, but ocean acidification is lowering the aragonite saturation state of seawater (Omega(a)). The downscaling of ocean acidification projections from global to GBR scales requires the set of regional drivers controlling Omega(a) to be resolved. Here we use a regional coupled circulation-biogeochemical model and observations to estimate the Omega(a) experienced by the 3,581 reefs of the GBR, and to apportion the contributions of the hydrological cycle, regional hydrodynamics and metabolism on Omega(a) variability. We find more detail, and a greater range (1.43), than previously compiled coarse maps of Omega(a) of the region (0.4), or in observations (1.0). Most of the variability in Omega(a) is due to processes upstream of the reef in question. As a result, future decline in Omega(a) is likely to be steeper on the GBR than currently projected by the IPCC assessment report