Application of COMPOCHIP Microarray to Investigate the Bacterial Communities of Different Composts

A microarray spotted with 369 different 16S rRNA gene probes specific to microorganisms involved in the degradation process of organic waste during composting was developed. The microarray was tested with pure cultures, and of the 30,258 individual probe-target hybridization reactions performed, there were only 188 false positive (0.62%) and 22 false negative signals (0.07%). Labeled target DNA was prepared by polymerase chain reaction amplification of 16S rRNA genes using a Cy5-labeled universal bacterial forward primer and a universal reverse primer. The COMPOCHIP microarray was applied to three different compost types (green compost, manure mix compost, and anaerobic digestate compost) of different maturity (2, 8, and 16 weeks), and differences in the microorganisms in the three compost types and maturity stages were observed. Multivariate analysis showed that the bacterial composition of the three composts was different at the beginning of the composting process and became more similar upon maturation. Certain probes (targeting Sphingobacterium, Actinomyces, Xylella/Xanthomonas/ Stenotrophomonas, Microbacterium, Verrucomicrobia, Planctomycetes, Low G + C and Alphaproteobacteria) were more influential in discriminating between different composts. Results from denaturing gradient gel electrophoresis supported those of microarray analysis. This study showed that the COMPOCHIP array is a suitable tool to study bacterial communities in composts

Differential adherence and expression of virulence traits by Candida albicans and Candida parapsilosis in mono- and dual-species cultures in artificial saliva

AIMS: To evaluate specific virulence factors of Candida albicans and Candida parapsilosis clinical oral isolates in mono- and dual-species culture in the presence of artificial saliva. METHODS AND RESULTS: Two of the strains used in this study were isolated from co-infection (C. albicans AM and C. parapsilosis AM2), and the other two were isolated from single infection (C. albicans AC and C. parapsilosis AD). The number of adhered yeast cells was measured and their enzymatic activity was determined simultaneously. In mono-species culture, C. parapsilosis strains adhered to a higher extent to the surface in comparison with the C. albicans strains. In dual-species culture, the C. parapsilosis strains adhered more in the presence of C. albicans AM. Interestingly, C. albicans AM and C. parapsilosis AD adhered to a higher extent when compared with all other co-cultures. In dual-species culture, the enzymatic activity of C. parapsilosis strains in the presence of C. albicans AC was higher than in the presence of C. albicans AM. CONCLUSIONS: The virulence factors of C. albicans and C. parapsilosis differ from strain to strain and are influenced by the presence of other species in culture. SIGNIFICANCE AND IMPACT OF THE STUDY: To understand the expression of virulence factors in Candida dual-species systems.This work was supported by Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BPD/20987/2004 attributed to Claudia Botelho

A Bayesian Framework to Account for Complex Non-Genetic Factors in Gene Expression Levels Greatly Increases Power in eQTL Studies

Gene expression measurements are influenced by a wide range of factors, such as the state of the cell, experimental conditions and variants in the sequence of regulatory regions. To understand the effect of a variable of interest, such as the genotype of a locus, it is important to account for variation that is due to confounding causes. Here, we present VBQTL, a probabilistic approach for mapping expression quantitative trait loci (eQTLs) that jointly models contributions from genotype as well as known and hidden confounding factors. VBQTL is implemented within an efficient and flexible inference framework, making it fast and tractable on large-scale problems. We compare the performance of VBQTL with alternative methods for dealing with confounding variability on eQTL mapping datasets from simulations, yeast, mouse, and human. Employing Bayesian complexity control and joint modelling is shown to result in more precise estimates of the contribution of different confounding factors resulting in additional associations to measured transcript levels compared to alternative approaches. We present a threefold larger collection of cis eQTLs than previously found in a whole-genome eQTL scan of an outbred human population. Altogether, 27% of the tested probes show a significant genetic association in cis, and we validate that the additional eQTLs are likely to be real by replicating them in different sets of individuals. Our method is the next step in the analysis of high-dimensional phenotype data, and its application has revealed insights into genetic regulation of gene expression by demonstrating more abundant cis-acting eQTLs in human than previously shown. Our software is freely available online at http://www.sanger.ac.uk/resources/software/peer/

Differential Actions of Chlorhexidine on the Cell Wall of Bacillus subtilis and Escherichia coli

Chlorhexidine is a chlorinated phenolic disinfectant used commonly in mouthwash for its action against bacteria. However, a comparative study of the action of chlorhexidine on the cell morphology of Gram-positive and Gram-negative bacteria is lacking. In this study, the actions of chlorhexidine on the cell morphology were identified with the aids of electron microscopy. After exposure to chlorhexidine, numerous spots of indentation on the cell wall were found in both Bacillus subtilis and Escherichia coli. The number of indentation spots increased with time of incubation and increasing chlorhexidine concentration. Interestingly, the dented spots found in B. subtilis appeared mainly at the hemispherical caps of the cells, while in E. coli the dented spots were found all over the cells. After being exposed to chlorhexidine for a prolonged period, leakage of cellular contents and subsequent ghost cells were observed, especially from B subtilis. By using 2-D gel/MS-MS analysis, five proteins related to purine nucleoside interconversion and metabolism were preferentially induced in the cell wall of E. coli, while three proteins related to stress response and four others in amino acid biosynthesis were up-regulated in the cell wall materials of B. subtilis. The localized morphological damages together with the biochemical and protein analysis of the chlorhexidine-treated cells suggest that chlorhexidine may act on the differentially distributed lipids in the cell membranes/wall of B. subtilis and E. coli

Exploring the potential of civic engagement to strengthen mental health systems in Indonesia (IGNITE) : a study protocol

Background Indonesia has the highest rate of years of life lost to disability or early death from Schizophrenia than any other country in the world. More than 90% of people with mental illness do not get any treatment and tens of thousands of people with psychosis are illegally detained ('pasung') in the family home. Civic engagement, a core part of the recent World Health Organisation global strategy, has the potential to address some of these challenges through the development of person-centered models of care. The aim of the study is to develop a testable systems level, culturally appropriate, civic engagement framework for use in Jakarta and Bogor, Indonesia to strengthen local mental health services. Methods A mixed methods study underpinned by a realist approach will be undertaken across four phases in two study sites in Indonesia (Jakarta and Bogor). Phase 1 will explore the use of civic engagement across South East Asia by conducting a systematic review of existing evidence. By surveying 300 mental health professionals, phase 2 will identify the stakeholders, the sources of collaboration and the evidence used by professionals in decision making within local mental health systems and identify potential opportunities for civic engagement within the system. In order to explore the potential use of civic engagement within Indonesian mental health services and identify priorities for a culturally appropriate framework, phase 3 will undertake two focus groups with participants with experience of psychosis or caring for someone with psychosis (n = 20–30). Professionals and other key decision makers in a range of roles across the system at a national (n = 5) and local level (n = 10–15/site) will also take part in semi-structured interviews. Phase 4 will co-produce a civic engagement framework for use in Indonesia by synthesising evidence from phases 1–3 collaboratively with key stakeholders. Discussion Civic engagement is a potential way in which health services in low and middle income countries can address the burden of mental health conditions through the development of person-centred models of care. However, such approaches are underexplored in Indonesia. This study will work with local stakeholders to design a testable civic engagement framework for use in mental health services in Indonesia

Crop Updates 2002 - Weeds

This session covers fifty eight papers from different authors: 1. INTRODUCTION Vanessa Stewart, DEPARTMENT OF AGRICULTURE INTEGRATED WEED MANAGEMENT IWM system studies / demonstration sites 2. Major outcomes from IWM demonstration sites, Alexandra Douglas Department of Agriculture 3. Integrated weed management: Katanning, Alexandra Douglas Department of Agriculture 4. Integrated weed management: Merredin, Vanessa Stewart Department of Agriculture 5. Long term resistance site: Get ryegrass numbers low and keep them low! Peter Newman and Glen Adams Department of Agriculture 6. Using pastures to manage ryegrass populations, Andrew Blake and Natalie Lauritsen Department of Agriculture Weed biology and competition 7. Understanding the weed seed bank life if important agricultural weeds, Sally Peltzer and Paul Matson Department of Agriculture 8. Consequence of radish competition on lupin nutrients in wheat-lupin rotation, Abul Hashem and Nerys Wilkins Department of Agriculture 9. Consequence of ryegrass competition on lupin nutrients in a wheat-lupin rotation, Abul Hashem and Nerys Wilkins Department of Agriculture 10. Brome grass too competitive for early sown wheat in a dry year at Mullewa, Peter Newman and Glenn Adam Department of Agriculture Crop establishment and weed management 11. Seeding rate, row spacing and herbicides for weed control, David Minkey Department of Agriculture 12. Effect of different seeding methods on wheat and ryegrass, Abul Hashem, Glen Riethmuller and Nerys Wilkins Department of Agriculture 13. Role of tillage implements and trifluralin on the effectiveness of the autumn tickle for stimulating annual ryegrass emergence, Tim Cusack1, Kathryn Steadman1 and Abul Hashem2,1Western Australia Herbicide Resistance Initiative, UWA; 2Department of Agriculture, 14. Timing of autumn tickle in important for non-wetting soils, Pippa Michael1, Peter Newman2 and Kathryn Steadman 2, 1Western Australia Herbicide Resistance Initiative, UWA, 2Department of Agriculture 15. Early investigation into weed seed burial by mouldboard plough, Sally Peltzer and Alex Douglas Department of Agriculture 16. Rolling post-emergent lupins to improve weed emergence and control on loamy sand, Paul Blackwell, Department of Agriculture and Dave Brindal, Strawberry via Mingenew IWM tools 17. Crop topping in 2001: How did we do? Peter Newman and Glenn Adam Department of Agriculture 18. Wickwipers work! Peter Newman and Glenn Adam Department of Agriculture 19. Wild radish and ryegrass seed collection at harvest: Chaff carts and other devices, Michael Walsh Western Australia Herbicide Resistance Initiative, UWA and Wayne Parker Department of Agriculture 20. Improving weed control in grazed pastures using legumes with low palatability, Clinton Revell, Giles Glasson Department of Agriculture, and Dean Thomas Faculty of Agriculture, University of Western Australia Adoption and modelling 21. Grower weed survey, Peter Newman and Glenn Adam Department of Agriculture 22. Agronomist survey, Peter Newman and Glenn Adam Department of Agriculture 23. Ryegrass RIM model stands the test of IWM field trial data, Alister Draper Western Australia Herbicide Resistance Initiative, UWA and Bill Roy, Western Australia Herbicide Resistance Initiative, UWA Agricultural Consulting and Research Services 24. Multi-species RIM: An update, Marta Monjardin1,2, David Pannell2 and Stephen Powles 1, 1Western Australia Herbicide Resistance Initiative, UWA, 2 ARE, University of Western Australia 25. RIM survey feedback, Robert Barrett-Lennard and Alister Draper Western Australia Herbicide Resistance Initiative, UWA 26. Effect of historic input and product prices on choice of ryegrass management strategies, Alister Draper1 and Martin Bent2, 1Western Australia Herbicide Resistance Initiative, UWA, 2Muresk Institute of Agriculture 27. Living with ryegrass – trading off weed control and economic performance, Martin Bent1 and Alister Draper2 , 1Muresk Institute of Agriculture, Curtin University, 2Western Australia Herbicide Resistance Initiative, UWA HERBICIDE RESISTANCE 28. Glyphosate resistance in WA and Australia: Where are we at? Paul Neve1, Art Diggle2, Patrick Smith3, Mechelle Owen1, Abul Hashem2, Christopher Preston4and Stephen Powles1,1Western Australian Herbicide Resistance Initiative, University of Western Australia, 2Department of Agriculture, 3CSIRO Sustainable Ecosystems, 4CRC for Australian Weed Management and Department of Applied and Molecular Ecology, Waite Campus, University of Adelaide 29. We need you weeds: A survey of knockdown resistance in the WA wheatbelt, Paul Neve1, Mechelle Owen1, Abul Hashem2 and Stephen Powles1 1Western Australian Herbicide Resistance Initiative, University of Western Australia, 2Department of Agriculture 30. A test for resistance testing, Mechelle Owen, Tracey Gillam, Rick Llewellyn and Steve Powles,Western Australia Herbicide Resistance Initiative, University of Western Australia 31. In field testing for herbicide resistance, a purpose built multi-treatment spray boom with results from 2001, Richard Quinlan, Elders Ltd 32. Advantages and limitations of a purpose built multi-treatment spray boom, Richard Quinlan, Elders Ltd 33. Group F resistant wild radish: What’s new? Aik Cheam, Siew Lee Department of Agriculture, and Mike Clarke Aventis Crop Science 34. Cross resistance of Brodal® resistant wild radish to Sniper®, Aik Cheam and Siew Lee, Department of Agriculture 35. Managing a biotype of wild radish with Group F and Group C resistance, Aik Cheam, Siew Lee, David Nicholson, Peter Newman Department of Agriculture and Mike Clarke, Aventis Crop Science HERBICIDE TOLERANCE 36. Herbicide tolerance of new wheat varieties, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Agriculture Western Australia 37. Response of barley varieties to herbicides, Harmohinder S. Dhammu, Terry Piper, Department of Agriculture 38. Tolerance of barley to phenoxy herbicides, Harmohinder S. Dhammu, Terry Piper, Department of Agriculture and Chad Sayer, Nufarm Australia Limited 39. Response of Durum wheats to herbicides, Harmohinder S. Dhammu, Terry Piper, Department of Agriculture 40. Response of new field pea varieties to herbicides, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture 41. Herbicide tolerance of Desi chickpeas on marginal soil, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture 42. Herbicide tolerance of newer lupin varieties, Terry Piper, Harmohinder Dhammu and David Nicholson, Department of Agriculture 43. Herbicide tolerance of some annual pasture legumes, Clinton Revell and Ian Rose, Department of Agriculture 44. Herbicide tolerance of pasture legumes, Andrew Blake, Department of Agriculture HERBICIDES – NEW PRODUCTS/PRODUCT USES; USE 45. Knockdown herbicides do not reliably kill small grass weeds, Peter Newman and Glenn Adam, Department of Agriculture 46. ‘Hair Cutting’ wheat with Spray.Seed®: Does it work? Peter Newman and Glenn Adam, Department of Agriculture 47. ‘Haircutting’: Does the number one cut work? Robert Barrett-Lennard1 and Jerome Critch2,1WA Herbicide Resistance Initiative, University of WA, 2Student, University of WA 48. Hammer EC (Carfentrazone-ethyl): A mixing partner for glyphosate to enhance the control of difficult broadleaf weeds, Gordon R. Cumming, Crop Care Australasia 49. Marshmallow control in reduced tillage systems, Sam Taylor, Wesfarmers Landmark 50. Herbicide options for summer germinating marshmallow, Vanessa Stewart, Department of Agriculture 51. Dual Gold® safe in a dry year at Coorow, Peter Newman and Glenn Adam, Department of Agriculture 52. The effect of glyphosate, paraquat and diquat as a crop topping application on the germination of barley, John Moore and Roslyn Jettner, Department of Agriculture 53. Herbicide options for melon control, Vanessa Stewart, Department of Agriculture 54. Herbicide options for the control of Chloris truncate (windmill grass) Vanessa Stewart, Department of Agriculture 55. Allelopathic effects of crop, pasture and weed residues on subsequent crop and pasture establishment, Stuart Bee1, Lionel Martin1, Keith Devenish2 and Terry Piper2, 1Muresk Institute of Agriculture, Curtin University of Technology, Northam, Western Australia, 2Centre for Cropping Systems, Department of Agriculture WEED ISSUES 56. Role of Roundup ReadyÒ canola in the farming system, Art Diggle1, Patrick Smith2, Paul Neve3, Felicity Flugge4, Amir Abadi5 and Stephen Powles3, 1Department of Agriculture; 2CSIRO, Sustainable Ecosystems; 3Western Australian Herbicide Resistance Initiative; 4Centre for Legumes in Mediterranean Agriculture; 5Touchstone Consulting 57. ’Weeds for Feed’ and livestock enterprise structures: A feasibility study and farmer survey in the north-easern wheatbelt, Duncan Peter and Stuart McAlpine, Department of Agriculture and Liebe Group, Buntine 58. e-weed, Vanessa Stewart, Agriculture Western Australi

Crop Updates 2007 - Farming Systems

This session covers forty papers from different authors: 1. Quality Assurance and industry stewardship, David Jeffries, Better Farm IQ Manager, Cooperative Bulk Handling 2. Sothis: Trifolium dasyurum (Eastern Star clover), A. Loi, B.J. Nutt and C.K. Revell, Department of Agriculture and Food 3. Poor performing patches of the paddock – to ameliorate or live with low yield? Yvette Oliver1, Michael Robertson1, Bill Bowden2, Kit Leake3and Ashley Bonser3, CSIRO Sustainable Ecosystems1, Department of Food and Agriculture2, Kellerberrin Farmer3 4. What evidence is there that PA can pay? Michael Robertson, CSIRO Floreat, Ian Maling, SilverFox Solutions and Bindi Isbister, Department of Agriculture and Food 5.The journey is great, but does PA pay? Garren Knell, ConsultAg; Alison Slade, Department of Agriculture and Food, CFIG 6. 2007 Seasonal outlook, David Stephens and Michael Meuleners, Department of Agriculture and Food 7. Towards building farmer capacity to better manage climate risk, David Beard and Nicolyn Short, Department of Agriculture and Food 8. A NAR farmers view of his farming system in 2015, Rob Grima, Department of Agriculture and Food 9. Biofuels opportunities in Australia, Ingrid Richardson, Food and Agribusiness Research, Rabobank 10. The groundwater depth on the hydrological benefits of lucerne and the subsequent recharge values, Ruhi Ferdowsian1and Geoff Bee2; 1Department of Agriculture and Food, 2Landholder, Laurinya, Jerramungup 11. Subsoil constraints to crop production in the high rainfall zone of Western Australia, Daniel Evans1, Bob Gilkes1, Senthold Asseng2and Jim Dixon3; 1University of Western Australia, 2CSIRO Plant Industry, 3Department of Agriculture and Food 12. Prospects for lucerne in the WA wheatbelt, Michael Robertson, CSIRO Floreat, Felicity Byrne and Mike Ewing, CRC for Plant-Based Management of Dryland Salinity, Dennis van Gool, Department of Agriculture and Food 13. Nitrous oxide emissions from a cropped soil in the Western Australian grainbelt, Louise Barton1, Ralf Kiese2, David Gatter3, Klaus Butterbach-Bahl2, Renee Buck1, Christoph Hinz1and Daniel Murphy1,1School of Earth and Geographical Sciences, The University of Western Australia, 2Institute for Meteorology and Climate Research, Atmospheric Environmental Research, Garmisch-Partenkirchen, Germany, 3The Department of Agriculture and Food 14. Managing seasonal risk is an important part of farm management but is highly complex and therefore needs a ‘horses for courses’ approach, Cameron Weeks, Planfarm / Mingenew-Irwin Group, Dr Michael Robertson, Dr Yvette Oliver, CSIRO Sustainable Ecosystems and Dr Meredith Fairbanks, Department of Agriculture and Food 15. Novel use application of clopyralid in lupins, John Peirce, and Brad Rayner Department of Agriculture and Food 16. Long season wheat on the South Coast – Feed and grain in a dry year – a 2006 case study, Sandy White, Department of Agriculture and Food 17. Wheat yield response to potassium and the residual value of PKS fertiliser drilled at different depths, Paul Damon1, Bill Bowden2, Qifu Ma1 and Zed Rengel1; Faculty of Natural and Agricultural Sciences, The University of Western Australia1, Department of Agriculture and Food2 18. Saltbush as a sponge for summer rain, Ed Barrett-Lennard and Meir Altman, Department of Agriculture and Food and CRC for Plant-based Management of Dryland Salinity 19. Building strong working relationships between grower groups and their industry partners, Tracey M. Gianatti, Grower Group Alliance 20. To graze or not to graze – the question of tactical grazing of cereal crops, Lindsay Bell and Michael Robertson, CSIRO Sustainable Ecosystems 21. Can legume pastures and sheep replace lupins? Ben Webb and Caroline Peek, Department of Agriculture and Food 22. EverGraze – livestock and perennial pasture performance during a drought year, Paul Sanford, Department of Agriculture and Food, and CRC for Plant-based Management of Dryland Salinity 23. Crop survival in challenging times, Paul Blackwell1, Glen Riethmuller1, Darshan Sharma1and Mike Collins21Department of Agriculture and Food, 2Okura Plantations, Kirikiri New Zealand 24. Soil health constraints to production potential – a precision guided project, Frank D’Emden, and David Hall, Department of Agriculture and Food 25. A review of pest and disease occurrence in 2006, Mangano, G.P. and Severtson, D.L., Department of Agriculture and Food 26. e-weed – an information resource on seasonal weed management issues, Vanessa Stewart and Julie Roche, Department of Agriculture and Food 27. Review of Pesticide Legislation and Policies in Western Australia, Peter Rutherford, BSc (Agric.), Pesticide Legislation Review, Office of the Chief Medical Adviser, WA Department of Health 28. Future wheat yields in the West Australian wheatbelt, Imma Farré and Ian Foster, Department of Agriculture and Food, Stephen Charles, CSIRO Land and Water 29. Organic matter in WA arable soils: What’s active and what’s not, Frances Hoyle, Department of Agriculture and Food, Australia and Daniel Murphy, UWA 30. Soil quality indicators in Western Australian farming systems, D.V. Murphy1, N. Milton1, M. Osman1, F.C. Hoyle2, L.K Abbott1, W.R. Cookson1and S. Darmawanto1; 1UWA, 2Department of Agriculture and Food 31. Impact of stubble on input efficiencies, Geoff Anderson, formerly employed by Department of Agriculture and Food 32. Mixed farming vs All crop – true profit, not just gross margins, Rob Sands and David McCarthy, FARMANCO Management Consultants, Western Australia 33. Evaluation of Local Farmer Group Network – group leaders’ surveys 2005 and 2006, Paul Carmody, Local Farmer Group Network, Network Coordinator, UWA 34. Seeding rate and nitrogen application and timing effects in wheat, J. Russell, Department of Agriculture and Food, J. Eyres, G. Fosbery and A. Roe, ConsultAg, Northam 35. Foliar fungicide application and disease control in barley, J. Russell, Department of Agriculture and Food, J. Eyres, G. Fosbery and A. Roe, ConsultAg, Northam 36. Brown manuring effects on a following wheat crop in the central wheatbelt, , J. Russell, Department of Agriculture and Food, J. Eyres, G. Fosbery and A. Roe, ConsultAg, Northam 37. Management of annual pastures in mixed farming systems – transition from a dry season, Dr Clinton Revell and Dr Phil Nichols; Department of Agriculture and Food 38. The value of new annual pastures in mixed farm businesses of the wheatbelt, Dr Clinton Revell1, Mr Andrew Bathgate2and Dr Phil Nichols1; 1Department of Agriculture and Food, 2Farming Systems Analysis Service, Albany 39. The influence of winter SOI and Indian Ocean SST on WA winter rainfall, Meredith Fairbanks and Ian Foster, Department of Agriculture and Food 40. Market outlook – Grains, Anne Wilkins, Market Analyst, Grains, Department of Agriculture and Foo

Chronic Helminth Infections Protect Against Allergic Diseases by Active Regulatory Processes

Developed countries are suffering from an epidemic rise in immunologic disorders, such as allergy-related diseases and certain autoimmunities. Several studies have demonstrated a negative association between helminth infections and inflammatory diseases (eg, allergy), providing a strong case for the involvement of helminth infections in this respect. However, some studies point in the opposite direction. The discrepancy may be explained by differences in frequency, dose, time, and type of helminth. In this review, new studies are discussed that may support the concept that chronic helminth infections in particular—but not acute infections—are associated with the expression of regulatory networks necessary for downmodulating allergic immune responses to harmless antigens. Furthermore, different components of regulatory networks are highlighted, such as the role of regulatory T and B cells, modulation of dendritic cells, early innate signals from structural cells (eg, epithelial cells), and their individual contributions to protection against allergic diseases. It is of great interest to define and characterize specific helminth molecules that have profound immunomodulatory capacities as targets for therapeutic application in the treatment or prophylaxis of allergic manifestations

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi