Systematic Review Protocol
Open Access
Are interventions to reduce the impact of arsenic contamination of groundwater on human health in developing countries effective?: a systematic review protocol
Environmental EvidenceThe official journal of the Collaboration for Environmental Evidence20111:1
https://doi.org/10.1186/2047-2382-1-1
© Pearson et al; licensee BioMed Central Ltd. 2011
Received: 28 September 2011
Accepted: 1 November 2011
Published: 1 November 2011
Abstract
Background
Chronic arsenic pollution is now recognised as a worldwide problem, with 21 countries experiencing arsenic groundwater contamination. It is a particularly important issue in developing countries, where groundwater is generally the preferred drinking source (as an alternative to polluted surface water). Technologies to remove or mitigate arsenic contamination of groundwater include pre-oxidation, adsorption, biological removal, and deep tubewells. Whilst technologies such as these may be effective in stable conditions (for example, at a laboratory scale), their effectiveness in real-world circumstances needs to be assessed to inform policy making.
Methods
This protocol details our proposed methods for conducting a systematic review to identify, appraise, and synthesise evidence to answer the following policy-relevant questions: a) In developing countries, are interventions to reduce the impact of arsenic contamination of groundwater on human health effective?, and b) What factors enable or constrain the effectiveness of these interventions in developing countries?
Keywords
Arsenic removal/mitigation Groundwater Human health Developing countries Systematic reviewBackground
Chronic arsenic pollution is now recognised as a worldwide problem, with 21 countries experiencing arsenic groundwater contamination. The largest population currently at risk is in Bangladesh, followed by West Bengal in India where groundwater concentrations frequently exceed the WHO guidelines (0.01 mgL-1) more than 10 fold [1, 2].
Within developing countries, groundwater is generally the preferred drinking source since it provides an alternative to polluted surface water and thereby reduces the incidence of water-borne diseases. However, the presence of unacceptably high levels of arsenic, which do not alter the taste, colour or odour of the water, has gone undetected for a number of years. As an element which is ubiquitous in many minerals, rocks and ores, arsenic is prone to natural weathering processes which enable its continual release into water as arsenite, As(III) and arsenate, As(V). Once in solution, both species display differences in bioavailability, reactivity and toxicity [3]. Additional inputs of arsenic from anthropogenic sources, such as mining and combustion of fossil fuels, further compound the problem.
Arsenic is one of the most toxic and carcinogenic of all the natural groundwater contaminants, available for ingestion directly in drinking water. The physical consequences of long term exposure to elevated concentrations of arsenic are severe. Conditions include skin, lung, bladder and kidney cancer as well as pigmentation changes, skin thickening (hyperkeratosis) neurological and circulatory disorders, muscular weakness, loss of appetite and nausea [4]. Hence, there is a clear need for interventions, whether technological or managerial, that reduce the concentration of arsenic in groundwater intended for human consumption according to WHO guidance (see Table 1).
Technology (Intervention) | Mechanism of action |
|---|---|
Pre-oxidation of arsenic(III) to arsenic(V) | By transforming to one form of arsenic, simplifies arsenic removal by other means |
Precipitation and coagulation | Co-precipitation of water insoluble arsenates and inorganic oxides of other metals |
Adsorption | Granular adsorptive media |
Membrane | Filtration, electrical repulsion and adsorption |
Ion exchange | Water passes through an ion exchange resin which removes arsenic by exchanging it for non-toxic ions. |
Biological removal | Sorption and oxidation, e.g. through bacteria, fungi and hyacinths |
Dugwell | The top of shallow aquifers, at less than 10 m, appear to be less contaminated than deeper water. |
Deep tubewells | Tubewells sunk below the layer of sediment considered to contain arsenic |
Reverse osmosis | Contaminated water is forced through a membrane. The treated water passes through leaving the arsenic ions on the membrane |
Nanofiltration | Similar principle to reverse osmosis, with a nm pore size |
Although interventions may be effective in stable conditions (for example, at a laboratory scale), their effectiveness in real-world circumstances needs to be assessed to inform policy making [5]. While correctly-maintained arsenic removal plants (ARPs) reduce levels of arsenic to safe values, an extensive programme to connect ARPs to tubewells in Bangladesh has resulted in many ARPs remaining unused or being actively rejected by communities [6, 7].
Objective of the review
Primary question
In developing countries, are interventions to reduce the impact of arsenic contamination of groundwater on human health effective?
Secondary question
What factors enable or constrain the effectiveness of these interventions in developing countries?
Methods
Search strategy
Literature specific to developing countries can often be difficult to retrieve, or of varying quality and/or suitability in answer to a research question. This has been noted particularly in the health field, where reliable information is often sparse and difficult to locate [8, 9].
The search approach proposed for this review, detailed below, aims to address these issues with a highly sensitive strategy applied in a variety of mixed-topic (for example, medical, geographical, and social science databases) interfaces [10]. This approach allows us to retrieve a broad evidence base of both quantitative and qualitative research and minimise the effect of bias.
Scoping
Preliminary scoping has been undertaken to assess the size and quality of the literature base for this review, and to test various approaches to defining the search syntax. Sample abstracts have confirmed the suitability of the search strategy and highlighted heterogeneity of the data.
Searching
A syntax laden intervention/population search would be inappropriate for this review given the variety of outcomes under consideration. Instead, using a simple yet sensitive approach allows a similar search to be used and consistency maintained between the many search interfaces, as well as allowing for cohesion in the overall search protocol.
See Additional File 1 for a sample search strategy written for Web of Science (ISI). This will be translated as appropriate for use in other search interfaces.
Search syntax
We have truncated Arsenic (arsen*) which gives us a variety of related expressions such as; arsenic, arsenates, arsenides, and arsenites, and will address the prevalent species found in groundwater [5]. It is not appropriate to specify terms such as 'arsenic contamination' or 'pollution' as this would prohibit a sensitive retrieval.
Population Terms
We propose searching with a broad sensitivity in regard to the population. Using water as a free-text term has, in scoping, captured all of the benchmarked papers with a sensitivity that precludes a need for a lengthy definition of synonyms.
Where it is necessary, we have defined terms which might not be captured on water alone. These terms, such as the noun 'groundwater', have been included as search terms in their own right.
Additional Terms
In mixed topic resources with no controlled indexing (such as Web of Science), we may require an additional developing countries filter to focus our results to the country populations under review. This filter will only be used in large mixed topic resources without formal indexing as a way to retain specificity. Its use and effect will be extensively checked prior to use by comparing the results obtained with and without using the filter.
The rationale for this filter is that by specifying the developing countries we know to exist, it minimises the risk of blocking outcomes which might be useful to the review, if for example we were to use a NOT cluster.
The country population filter has been developed using AusAID's list of developing countries (http://www.ausaid.gov.au/ngos/devel_list.cfm) which has been cross-checked with the International Human Development Indicators (http://hdr.undp.org/en/statistics/). The International Monetary Fund's (IMF) list of Emerging and Developing Countries was referenced in testing the strategy but the metric was thought to be largely based upon economic outputs and therefore did not correlate with the aims of the filter and expression of the project (http://www.imf.org/external/pubs/ft/weo/2010/01/weodata/groups.htm#oem).
To retain sensitivity, the filter uses a mixture of generic terms such as, 'Developing Countries,' coupled with naming and referencing developing countries and their inhabitants. We have also included countries such as Taiwan, which is considered a newly emerged country, as the date parameters of search pre-date their change of status.
It is likely that this filter will only be used in Web of Science to help control the balance of retrieval. Where it is used, extensive testing to cross-check the retrieval will be conducted. A narrative will be recorded with each search which uses this filter to explain its use.
Limits
All searching will be limited: 1990-Current (the period in which arsenic contamination of groundwater became widely recognised and interventions to address the problem were introduced). Searches will be limited to the English language, as scoping searches indicate that this is the language of publication for scientific studies in countries where arsenic contamination of groundwater is an issue.
Search Resources
The literature-base required to sufficiently answer all aspects of the question needs to be drawn from a variety of topical areas, including; health, engineering, geography and sociology, as well as databases specifically focused on developing countries [11]. Therefore we propose a mixed-topical approach for this review in online databases and catalogues (Box 1).
As not all relevant data are indexed within databases, searching web-resources and web-sites ensures a complete approach and minimises the risk of bias [12]. The resources shown in Box 2, along with conference abstracts and Google, [13] will help us locate grey literature [14]. The search terms used will be arsen* and water and the date of searching will be recorded.
Search Sources: Other Sources
In addition to searching the resources above, we propose to employ 'pearl-growing' techniques [15], such as: Citation chasing from included references, "Forwards" citation chasing on included references using citation databases (Science Citation Index/Social Science Citation Index) to check if any new papers have cited the paper in question since it was published, and contacting authors of included studies [16, 17].
Search Results
The exported files from the searching will be uploaded and de-duplicated in Endnote X4 (Thompson Reuters). Where an export is not possible, for example from a resource without RIS functionality, the data will be exported to a word file and saved.
The searches will be recorded using PRISMA guidelines [18]. This will include the list of databases searched (with their data parameters), recording of the date searched and the strategy as run. Limits applied, the results yielded and an accurate recording of the de-duplication process will be annotated in a search annex.
Study inclusion criteria
Titles and abstracts of all studies located by the search strategy will be screened for inclusion by a reviewer (with a random sample of 10% being checked by a second reviewer) according to the criteria below. Where it is not clear from the title and abstract alone if the study meets the inclusion criteria, the full-text of the study will be obtained to enable assessment (with a random sample of 10% being checked by a second reviewer). Any disagreements about whether a study meets the inclusion criteria will be resolved by discussion, with the involvement of a third reviewer if necessary. All studies to be included must have been published from 1990 onwards and in the English language. The PICO format (population, intervention, comparators, and outcomes) will be used to define study inclusion criteria:
Population (or 'subject')
People living in developing countries (as defined by AusAID: http://www.ausaid.gov.au/ngos/devel_list.cfm)
Intervention
Any technology (see Table 1) designed to remove or lower arsenic concentration in water intended for human consumption. This does NOT include national or local policy or specific educational interventions.
Comparators
Pre/post comparison, comparison with another technology intended to remove or lower arsenic concentration in groundwater, or comparison with no intervention.
Outcomes (must be measured in field-based studies)
- 1)
Arsenic concentration in groundwater intended for human consumption
- 2)
Arsenic concentration in human tissue or body fluids.
- 3)
Observation of people's behaviour relating to technologies intended to remove or lower arsenic concentration in groundwater intended for human consumption
- 4)
People's knowledge or attitudes relating to technologies intended to remove or lower arsenic concentration in groundwater intended for human consumption
The above outcomes are listed hierarchically according to the accuracy with which they are likely to measure the effectiveness of interventions; for example, arsenic concentration in groundwater is considered a more accurate measure of an intervention's effectiveness than people's knowledge or attitudes. Nevertheless, all of the above outcomes may provide useful measures of interventions' effectiveness. However, there is a possibility that the number of outcome measures in included studies is such that the production of a rigorous review that includes all of these outcomes, within the time and resources available, would be unrealistic. In this eventuality, in consultation with AusAID and with a view to optimising the review's potential to inform policy making, we shall either exclude those outcomes that are more distant measures of interventions' effectiveness or exclude studies rated as 'weak' by the quality appraisal tool.
Types of study
For the synthesis of effectiveness data, only comparative study designs will be included (including, but not limited to, randomised controlled trials, before and after studies, and cross-sectional studies). If a recent and high quality systematic review that substantively answers an aspect of the review questions is located, we shall (in consultation with AusAID) utilise the review as a source of potentially includable studies, and update and extend it if it is considered feasible to do so.
Potential effect modifiers and reasons for heterogeneity
The contexts in which technologies designed to remove or lower arsenic concentration in groundwater are implemented may have a significant impact on their effectiveness [19, 20]. Education about technologies, level of community development, the acceptability of interventions, and/or national policy may act as important effect modifiers. Additional effect modifiers identified in included studies will be recorded so that their impact on the effectiveness of interventions can be assessed.
Study quality assessment
Comparative study designs reporting quantitative data will be assessed using the McMaster University Effective Public Health Practice Project quality appraisal tool (http://www.ephpp.ca/tools.html). This tool is suitable for use across a wide range of quantitative study designs and has explicit criteria for rating studies as 'strong', 'moderate', or 'weak'. The tool also includes criteria for assessing implementation fidelity, which may be of particular importance when considering the implementation of arsenic removal (or mitigation) technologies or water management practices in the developing world.
Study quality appraisal will be conducted by one reviewer, with a random sample of 25% checked by a second reviewer. Disagreements will be resolved by discussion, with the involvement of a third reviewer if necessary.
Data extraction strategy
Data will be extracted from included studies by one reviewer using a modified version of a data extraction form designed for use with complex public health studies [21] - see Additional File 2. A random sample of at least 10% of the completed data extraction forms will be checked by a second reviewer. Discrepancies will be resolved by discussion, with the involvement of a third reviewer if necessary. The data to be extracted will follow the outcomes described above and will also include details of the population, type of intervention, and context in which implemented.
Data synthesis and presentation
The quality of the included studies will be assessed using, where available, appropriate checklists for the studies (e.g. EPHPP quality assessment tool for quantitative studies).
The extracted data are likely to be heterogeneous in terms of the interventions assessed, the outcomes reported, the study design, and population, among others. These differences will have to be evaluated qualitatively to determine whether quantitative synthesis using meta-analysis methods will produce meaningful results (e.g. are processes similar between countries to allow synthesis of results across different countries? Or would it be preferable to limit analyses by country?). If study results are deemed to be comparable but are reported using different outcomes measures (e.g. odds ratios or mean differences), methods are available to translate outcome measures on the same scale to assist meta-analysis [22].
If groups of results are deemed to be comparable, an assessment of their statistical heterogeneity will be made using the I2 statistic [23]. This will help to inform whether the data are too heterogeneous (statistically) to provide useful results when combined. The possibility of reporting/publication biases will be assessed where available. However, we are aware that such techniques (funnel plot, regression tests [24]) perform poorly when the number of comparable study results to be assessed is small, as could be the case with this review.
Depending on the heterogeneity between study results either fixed effects or random effects meta-analysis methods will be used to analyse the extracted data. The fixed effects method assumes that the only variation between study results is that due to sampling error and so will be appropriate where the I2 statistic indicates mild heterogeneity. On the other hand, the random effects method assumes that there is variation between studies beyond that due to sampling error, and so will be appropriate where greater heterogeneity is present. Note that the random effects model accounts for heterogeneity, but does not help to explain potential sources of heterogeneity. To explore possible sources of heterogeneity we will undertake subgroup analyses and, where the number of study results allows, meta-regression.
Sensitivity analyses will be undertaken to explore the impact of study quality, possible reporting/publication bias and factors related to study design on the meta-analysis estimates.
To enable the synthesised quantitative data about the effectiveness of interventions to be understood in the light of relevant contextual factors, narrative synthesis tools and techniques such as grouping, tabulation, conceptual mapping, and sub-group analyses [25] will be used.
Box 1 Online databases and catalogues
Assia via CSA
Biosis Previews via ISI
CAB Abstracts*
Conference Proceedings Citation Index-Science (CPCI-S) +
Conference Proceedings Citation Index-Social Science & Humanities (CPCI-SSH) +
Embase via OVID
ERIC via Dialog
GreenFILE via Ebsco
HMIC via OVID
Inspec via ISI
International Bibliography of the Social Sciences (IBSS) via Proquest
Lilacs database via http://lilacs.bvsalud.org/en/
Medline via Ovid
NTIS database via Engineering Village*
Pollution Abstracts*
PsycINFO via Ovid
Science Citation Index Expanded (SCI-EXPANDED) +
Scopus
Social Sciences Citation Index (SSCI) +
Sociological Abstracts via CSA
Worldwide Political Science Abstracts (WPSA) via CSA
* resource to be accessed from the British Library
+ resources to be searched through the Web of Science interface (ISI)
Box 2 Searchable Web-databases and Web-sites
British Library for Development Studies (BDLS)
Directory of Open Access Journals
ELDIS
Evidence-Based Policy in Development Network (EBPDN)
Global Development Network (GDN)
Index to Theses
JOLIS
RAPID (Research and Policy in Development)
The World Bank
WHOLIS (World Health Organisation)
WHO Regional Databases
BL (British library) Direct
African Development Bank
African Medical and Research Control,
Asian Development Bank
Australian Aid Agency
British Geographical Survey
Canadian International Development Agency
Centers for Disease Control and Prevention
Christian Aid
Danish Development Agency
Department for International Development
European Commission
Fresh Water Action Network
GTZ
Inter-American Development Bank
International Rescue Committee
International Water Management Institute
IRC International
Japan Bank for International Cooperation
Japan International Cooperation Agency
organisations of the United Nations (UNICEF, UNEP, UNDP, UN-HABITAT, UNRISD, FAO)
Oxfam
Overseas Development agency
Pan American Health Organization
Red Cross
Swedish development agency
the World Bank (Office of Evaluation and Development)
US Agency for International Development
Water and Sanitation Centre
WaterAid
World Health Organization
Declarations
Acknowledgements
The systematic review for which this protocol has been developed is funded by the Australian Agency for International Development (AusAID) (Agreement number 59617). Funding for development of the review proposal was provided by the National Institute for Health Research (NIHR) Peninsula Collaboration for Leadership in Applied Health Research & Care (PenCLAHRC). The views expressed in this publication are those of the authors and not necessarily those of the NHS, NIHR or the Department of Health.
Authors’ Affiliations
(1)
Peninsula Technology Assessment Group (PenTAG), Peninsula College of Medicine & Dentistry (University of Exeter)
(2)
Peninsula Collaboration for Leadership in Applied Health Research & Care (PenCLAHRC), Peninsula College of Medicine & Dentistry (University of Exeter)
(3)
Peninsula Technology Assessment Group (PenTAG)/Peninsula Collaboration for Leadership in Applied Health Research & Care (PenCLAHRC), Peninsula College of Medicine & Dentistry (University of Exeter)
(4)
School of Geography, Earth and Environmental Sciences, University of Plymouth
(5)
European Centre for Environment & Human Health, Knowledge Spa, Royal Cornwall Hospital, Peninsula College of Medicine & Dentistry (University of Exeter)
References
- Rahman MM, Mukherjee D, Sengupta MK, Chowdhury UK, Lodh D, Chanda CR, Roy S, Selim M, Quamruzzaman Q, Milton AH, et al.: Effectiveness and reliability of arsenic field testing kits: Are the million dollar screening projects effective or not? Environmental Science & Technology 2002,36(24):5385–5394. 10.1021/es020591oView ArticleGoogle Scholar
- Sarkar S, Blaney L, Gupta A, Ghosh D, Sengupta A: Arsenic removal from groundwater and its safe containment in a rural environment: Validation of a sustainable approach. Environmental Science and Technology 2008, 42: 4268–4273. 10.1021/es702556tView ArticleGoogle Scholar
- Villaescus I, Bollinger J-C: Arsenic in drinking water: sources, occurence and health effects (a review). Rev Environ Sci Biotechnol 2008, 7: 307–323. 10.1007/s11157-008-9138-7View ArticleGoogle Scholar
- Mohan D, Pittman CU Jr: Arsenic removal from water/wastewater using adsorbents - A critical review. Journal of Hazardous Materials 2007, 142: 1–53. 10.1016/j.jhazmat.2007.01.006View ArticleGoogle Scholar
- Kinniburgh DG, Smedley PL, (eds.): Arsenic contamination of groundwater in Bangladesh, Volume 2: Final report (British Geological Survey WC/00/19). Keyworth: British Geological Survey; 2001.Google Scholar
- Hossain A, Sengupta M, Ahamed S, Rahman M, Mondal D, Lodh D, Das B, Nayak B, Roy B, Mukherjee A, et al.: Ineffectiveness and poor reliability of arsenic removal plants in West Bengal, India. Environmental Science and Technology 2005,39(11):4300–4306. 10.1021/es048703uView ArticleGoogle Scholar
- Srikanth R: Challenges of sustainable water quality management in rural India. Current Science 2009,97(3):317–325.Google Scholar
- Raban MZ, Dandona R, Dandona L: Essential health information available for India in the public domain on the internet. BMC Public Health 2009,9(1):208–208. 10.1186/1471-2458-9-208View ArticleGoogle Scholar
- The Lancet: Stumbling around in the dark. The Lancet 2005,365(9476):1983–1983. 10.1016/S0140-6736(05)66671-8View ArticleGoogle Scholar
- Betrán AP, Say L, Gulmezoglu AM, Hampson L: Effectiveness of different databases in identifying studies for systematic reviews: experience from the WHO systematic review of maternal morbidity and mortality. BMC Medical Research Methodology 2005.,5(6):Google Scholar
- Rodriguez K: The information search in Latin America: an analysis of Latin American databases. Libri 1993,43(3):245–262. 10.1515/libr.1993.43.3.245View ArticleGoogle Scholar
- Gomersall A, Cooper C: Database selection bias and its affect on systematic reviews: a United Kingdom perspective. Joint Colloquium of the Cochrane and Campbell Collaborations, October 2010; 2010.Google Scholar
- Tomlinson R, Rizvi A, Salinas R, Garry S, Pehr J, Rodriguez F: The Influence of Google on Urban Policy in Developing Countries. International Journal of Urban and Regional Research 2010,34(1):174–189. 10.1111/j.1468-2427.2010.00933.xView ArticleGoogle Scholar
- Otike J: The acquisition of grey literature in developing countries. Proceedings of the First International Conference on Grey Literature held at the RAI Congress Centre 1994.Google Scholar
- Papaioannou D, Sutton AJ, Carroll C, Booth A, Wong R: Literature searching for social science systematic reviews: consideration of a range of techniques. Health Information and Libraries Journal 2010,27(2):114–122.View ArticleGoogle Scholar
- Greenhalgh T, Peacock R: Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources. BMJ 2005,331(7524):1064–1064. 10.1136/bmj.38636.593461.68View ArticleGoogle Scholar
- Schlosser RW, Wendt O, Bhavnani S, Nail-Chiwetalu B: Use of information seeking strategies for developing systematic reviews and engaging in evidence-based practice: the application of traditional and comprehensive Pearl Growing. A review. International Journal of Language & Communication Disorders 2006,41(5):567–582. 10.1080/13682820600742190View ArticleGoogle Scholar
- Moher D, Liberati A, Tetzlaff J, Altman DG, The PG: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009.,339(jul21 1): b2535-b2535-b2535-b2535.Google Scholar
- Atkins P, Hassam M, Dunn C: Poisons, pragmatic governance and deliberative democracy: The arsenic crisis in Bangladesh. Geoforum 2007, 38: 155–170. 10.1016/j.geoforum.2006.07.009View ArticleGoogle Scholar
- Ahmed M, Ahuja S, Alauddin M, Hug S, Lloyd J, Pfaff A, Pichler T, Saltikov C, Stite M, van Green A: Ensuring safe drinking water in Bangladesh. Science 2006, 314: 1687–1688. 10.1126/science.1133146View ArticleGoogle Scholar
- National Institute for Health & Clinical Excellence: Methods for the development of NICE public health guidance. 2nd edition. London: National Institute for Health & Clinical Excellence; 2009.Google Scholar
- Chinn S: A simple method for converting an odds ratio to effect size for use in meta-analysis. Statistics in Medicine 2000, 19: 3127–3131. 10.1002/1097-0258(20001130)19:22<3127::AID-SIM784>3.0.CO;2-MView ArticleGoogle Scholar
- Higgins JPT, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 2003, 327: 557–560. 10.1136/bmj.327.7414.557View ArticleGoogle Scholar
- Higgins JPT, Green S, (eds.): Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011.Google Scholar
- Popay J, Roberts H, Sowden A, Petticrew M, Arai L, Rodgers M, Britten N: Guidance on the Conduct of Narrative Synthesis in Systematic Reviews: A Product from the ESRC Methods Programme. 2006.Google Scholar
- Malik AH, Khan ZM, Mahmood Q, Nasreen S, Bhatti ZA: Perspectives of low cost arsenic remediation of drinking water in Pakistan and other countries. Journal of Hazardous Materials 2009,168(1):1–12. 10.1016/j.jhazmat.2009.02.031View ArticleGoogle Scholar
- Heikens A: Arsenic contamination of irrigation water, soil and crops in Banlgadesh: Risk implications for sustainable agriculture and food safety in Asia. Volume 20. Edited by: Organisation FaA. Bangkok: RAP; 2006.Google Scholar
Copyright
© Pearson et al; licensee BioMed Central Ltd. 2011
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
