The relationship between study sponsorship,risks of bias,and research outcomes in atrazine exposure studies conducted in non-human animals: Systematic review and meta-analysis

BackgroundA critical component of systematic review methodology is the assessment of the risks of bias of studies that are included in the review. There is controversy about whether funding source should be included in a risk of bias assessment of animal toxicology studies.ObjectiveTo determine whether industry research sponsorship is associated with methodological biases, the results, or conclusions of animal studies examining the effect of exposure to atrazine on reproductive or developmental outcomes.MethodsWe searched multiple electronic databases and the reference lists of relevant articles to identify original research studies examining the effect of any dose of atrazine exposure at any life stage on reproduction or development in non-human animals. We compared methodological risks of bias, the conclusions of the studies, the statistical significance of the findings, and the magnitude of effect estimates between industry sponsored and non-industry sponsored studies.ResultsFifty-one studies met the inclusion criteria. There were no differences in methodological risks of bias in industry versus non-industry sponsored studies. 39 studies tested environmentally relevant concentrations of atrazine (11 industry sponsored, 24 non-industry sponsored, 4 with no funding disclosures). Non-industry sponsored studies (12/24, 50.0%) were more likely to conclude that atrazine was harmful compared to industry sponsored studies (2/11, 18.1%) (p value = 0.07). A higher proportion of non-industry sponsored studies reported statistically significant harmful effects (8/24, 33.3%) compared to industry-sponsored studies (1/11; 9.1%) (p value = 0.13). The association of industry sponsorship with decreased effect sizes for harm outcomes was inconclusive.ConclusionOur findings support the inclusion of research sponsorship as a risk of bias criterion in tools used to assess risks of bias in animal studies for systematic reviews. The reporting of other empirically based risk of bias criteria for animal studies, such as blinded outcome assessment, randomization, and all animals included in analyses, needs to improve to facilitate the assessment of studies for systematic reviews.     

Application of the Navigation Guide systematic review methodology to the evidence for developmental and reproductive toxicity of triclosan

BackgroundThere are reports of developmental and reproductive health effects associated with the widely used biocide triclosan.ObjectiveApply the Navigation Guide systematic review methodology to answer the question: Does exposure to triclosan have adverse effects on human development or reproduction?MethodsWe applied the first 3 steps of the Navigation Guide methodology: 1) Specify a study question, 2) Select the evidence, and 3) Rate quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using pre-specified criteria. We assessed the number and type of all relevant studies. We evaluated each included study for risk of bias and rated the quality and strength of the evidence for the selected outcomes. We conducted a meta-analysis on a subset of suitable data.ResultsWe found 4282 potentially relevant records, and 81 records met our inclusion criteria. Of the more than 100 endpoints identified by our search, we focused our evaluation on hormone concentration outcomes, which had the largest human and non-human mammalian data set. Three human studies and 8 studies conducted in rats reported thyroxine levels as outcomes. The rat data were amenable to meta-analysis. Because only one of the human thyroxine studies quantified exposure, we did not conduct a meta-analysis of the human data. Through meta-analysis of the data for rats, we estimated for prenatal exposure a 0.09% (95% CI: − 0.20, 0.02) reduction in thyroxine concentration per mg triclosan/kg-bw in fetal and young rats compared to control. For postnatal exposure we estimated a 0.31% (95% CI: − 0.38, − 0.23) reduction in thyroxine per mg triclosan/kg-bw, also compared to control. Overall, we found low to moderate risk of bias across the human studies and moderate to high risk of bias across the non-human studies, and assigned a “moderate/low” quality rating to the body of evidence for human thyroid hormone alterations and a “moderate” quality rating to the body of evidence for non-human thyroid hormone alterations.ConclusionBased on this application of the Navigation Guide systematic review methodology, we concluded that there was “sufficient” non-human evidence and “inadequate” human evidence of an association between triclosan exposure and thyroxine concentrations, and consequently, triclosan is “possibly toxic” to reproductive and developmental health. Thyroid hormone disruption is an upstream indicator of developmental toxicity. Additional endpoints may be identified as being of equal or greater concern as other data are developed or evaluated.     

Reflections on the process of using systematic review techniques to evaluate the literature regarding the neurotoxicity of low level exposure to organophosphate pesticides

We undertook a systematic review (incorporating meta-analysis) of the literature concerning the neurotoxicity of cumulative low level occupational exposure to organophosphate pesticides, which was published online by the journal Critical Reviews in Toxicology in 2012. As far as we are aware, we were the first research team to attempt quantitative evaluation of study findings on this topic, using meta-analysis. We wish to encourage others to apply systematic review techniques in chemical risk assessment to reduce bias, increase transparency and better inform public policy. We thought it would be useful to share our experience of undertaking a systematic review in the hope of dispelling misconceptions about the complexity, time and resource issues involved along with the view that meta-analysis is meaningless when studies are not homogeneous. In this commentary paper we reflect on aspects of the process which were relatively straightforward; aspects which were more challenging; the advantages of using systematic review techniques; and the advantages and limitations of using statistical techniques such as meta-analysis in this context.     

A holistic approach to Concentration Assessment of hazards in the risk assessment of landfill leachate

Risk assessment is a new research area. The risk assessment research area deals with a wide range of issues other than landfills. Examples of these issues are Radiation, Food Industry, Ecology, Epidemiology, etc. The authors have found that there are generic elements in risk assessment and these elements are independent of the subject areas mentioned above. An important example of these generic elements is the Concentration Assessment of hazards and is equally important from the perspective of landfill risk assessment. Furthermore, in the literature review of landfill risk assessment approaches, no evidence has been discovered of a holistic risk assessment methodology for landfill gas, leachate, or degraded landfill waste. A range of knowledge deficiencies has been found in the literature reviewed to date. One of these deficiencies in knowledge is the lack of a holistic procedure for carrying out Concentration Assessment. From the perspective of landfill leachate, this paper discusses the extent to which the Concentration Assessment of hazards is absent in landfill risk assessment approaches described in the literature reviewed to date, and the elements that should be added to the procedure of the Concentration Assessment in order to enhance the process of risk assessment. The paper also briefly outlines a holistic procedure for the Concentration Assessment and a corresponding computer model for the risk assessment of landfill leachate.     

Guidance on assessing the methodological and reporting quality of toxicologically relevant studies: A scoping review

Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type. In general, we found considerable guidance for in vivo and human studies, but only one paper addressed in vitro studies exclusively. The guidance for (Q)SAR studies and physico-chemical studies was scant but authoritative. There was substantial overlap across guidance documents in the proposed criteria for both methodological and reporting quality. Some guidance documents address toxicology research directly, whereas others address preclinical research generally or clinical research and therefore may not be fully applicable to the toxicology context without some translation. Another challenge is the degree to which assessments of methodological quality in toxicology should focus on risk of bias – as in clinical medicine and healthcare – or be broadened to include other quality measures, such as confirming the identity of test substances prior to exposure. Our review is intended primarily for those in toxicology and risk assessment seeking an entry point into the extensive and diverse literature on methodological and reporting quality applicable to their work.     

Determination of causes of death in animal survival experiments

Life-span studies, using the laboratory mouse, are an efficient means for determining potential chronic toxicity of various materials. However, difficulties that affect the analysis of the data include (1) incomplete and missing observations due to canabilism or autolysis, (b) possible differences in overall mortality rate between treated and control populations that preclude assessments based upon observed final incidence, and (c) potential interaction between specific pathological states. Being aware of these difficulties does not eliminate their consequence, but careful attention to ascertaining the presence or absence of a disease state coupled with an assessment of its significance for each individual can allow greater confidence to be placed in data obtained from survival studies. The question of possible interaction between disease states is better approached experimentally by judicious use of serial killing to define age-specific disease prevalence.Many diseases are difficult to identify in animals as small as the mouse. At the other extreme, too much importance may be attributed to some disease states, not because of their lethality, but because of their ease of detection. One way to minimize the uncertainties introduced by conscious and unconscious observational bias is to adhere to a highly systematic tissue examination of every animal, regardless of condition of apparent cause of death. Through application of well-defined and stable diagnostic criteria a better appreciation can be obtained of the full spectrum of lethal and incidental pathologies observed in animals dying throughout the survival study.     

Chemical plant risk assessment: Uncertainties and development needs

A brief review is given covering the development of major hazards risk assessment since the Flixborough disaster of 1974, with special reference to the introduction of new regulations. The importance of risk assessment in the management of major hazards is discussed by reference to the Canvey Island studies, and it is suggested that the problem of uncertainties in the estimation of risks by analysis has not been adequately treated. Examples are given to illustrate the magnitude of such uncertainties in the consequence modelling of accidental releases from a chemical plant. In addition to suggested development needs in risk analysis techniques, topics are suggested which call for development in the evaluation and management of risks.     

Fuzzy synthetic evaluation of treated wastewater reuse for agriculture

Reuse of treated wastewater (TWW) for agriculture is in practice in many countries. TWW reuse requires wastewater collection, treatment and recycling, which is associated with cost as well as risk to human and ecological systems. In contrast, it can increase agricultural production and reduce environmental risks by reducing wastewater discharge into the natural environment. In Saudi Arabia, where available water resources are extremely limited, TWW reuse can save significant amount of non-renewable groundwater used in agricultural development, which is a strategic goal for the country. In this paper, a multicriteria decision-making approach was developed where cost, risk, benefits and social acceptance of TWW reuse were considered to be the main criteria. A multistage hierarchy risk management model was constructed for this evaluation. Fuzzy synthetic evaluation technique was incorporated where fuzzy triangular membership functions were developed to capture uncertainties of the basic criteria. The analytic hierarchy process was used to determine the relative importance of various criteria at different hierarchy levels. This study indicated that TWW reuse could have positive impact on agriculture, risk reduction and groundwater conservation.     

Integrating disaster risk reduction and climate change adaptation: key challenges—scales, knowledge, and norms

Statistical data shows that the increase in disasters due to natural hazards over the past 20 years has, for the most part, been caused by meteorological and hydrological events. This increase has been largely assigned to climate change [Centre for Research on the Epidemiology of Disasters (CRED), 2010, http://www.emdat.be/Database/Trends/trends.html], that is, with climate-related hazards being major triggers for the majority of disasters. Consequently, there is obvious concern about how a changing climate will exacerbate the situation in the future (McBean and Ajibade in Curr Opin Environ Sustain 1:179–186, 2009). However, the attribution of a single hazard event or specific losses to climate change is still difficult, if not impossible, due to the complexity of factors that generate disaster losses. Disaster risk is a product of the interaction of the hazard (event) and the vulnerability conditions of the society or elements exposed. As a result, the need for a systematic linkage between disaster risk reduction (DRR) and climate change adaptation (CCA) to advance sustainable development, and finally human security is being discussed within the ongoing climate change negotiations as well as within the disaster risk community, for example, in the framework of the Intergovernmental Panel on Climate Change special report on ‘Managing the risks of extreme events and disasters to advance climate change adaptation’. However, crucial differences between DRR and CCA exist that have widely limited or hampered their integration in practice. A review of existing literature on the topic and current national and local adaptation strategies, as well as 38 expert interviews conducted between April and May 2009, have led the authors to hypothesise that most of these differences and challenges can be categorised with respect to different spatial and temporal scales, the knowledge base, and norm systems. This paper examines the reasons for the practical barriers when linking CCA and DRR according to these three aspects. Finally, we outline recommendations and measures that need to be adopted in order to overcome existing barriers. In addition, quality criteria are formulated that should be applied in order to constantly monitor and evaluate adaptation strategies designed to simultaneously meet DRR requirements and vice versa.     

GRADE: Assessing the quality of evidence in environmental and occupational health

There is high demand in environmental health for adoption of a structured process that evaluates and integrates evidence while making decisions and recommendations transparent. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework holds promise to address this demand. For over a decade, GRADE has been applied successfully to areas of clinical medicine, public health, and health policy, but experience with GRADE in environmental and occupational health is just beginning. Environmental and occupational health questions focus on understanding whether an exposure is a potential health hazard or risk, assessing the exposure to understand the extent and magnitude of risk, and exploring interventions to mitigate exposure or risk. Although GRADE offers many advantages, including its flexibility and methodological rigor, there are features of the different sources of evidence used in environmental and occupational health that will require further consideration to assess the need for method refinement. An issue that requires particular attention is the evaluation and integration of evidence from human, animal, in vitro, and in silico (computer modeling) studies when determining whether an environmental factor represents a potential health hazard or risk. Assessment of the hazard of exposures can produce analyses for use in the GRADE evidence-to-decision (EtD) framework to inform risk-management decisions about removing harmful exposures or mitigating risks. The EtD framework allows for grading the strength of the recommendations based on judgments of the certainty in the evidence (also known as quality of the evidence), as well as other factors that inform recommendations such as social values and preferences, resource implications, and benefits. GRADE represents an untapped opportunity for environmental and occupational health to make evidence-based recommendations in a systematic and transparent manner. The objectives of this article are to provide an overview of GRADE, discuss GRADE's applicability to environmental health, and identify priority areas for method assessment and development.     

Areas of uncertainty in comparing risks of energy systems

In the past, the safety of technology has mainly been ensured by deterministic criteria that were based on engineering principles and on experience. Recently, however, it has become necessary to include risk assessment into safety policy. This need arises due to the order of magnitude of possible health and environmental impact from normal operation or accidents, as well as the complexity of modern systems that no longer allow for intuitive understanding of possible accident sequences. Assessment of risks of technical installations is subject to large uncertainties that are caused by lack of data and inadequate quantification and evaluation methods. This paper reviews the main areas of uncertainties with regard to their importance for decisionmaking. Uncertainties are an inherent part of any risk assessment result and can never be avoided. It is thus important to pay particular attention to them including limitations of methods, sensitivity to assumptions about parameters, and site-specific considerations. All this information must be described in great detail so that it can be integrated into the decisionmaking process. If applied in this context, risk assessment is a useful tool for identifying major contributors to risk and effective actions of risk management.     

Overview and definition of risk: Its assessment and management

Risk assessment includes both risk estimation (identifying hazards and estimating their outcomes and probabilities) and risk evaluation (determining the significance or value of risks to those concerned with or affected by the decision). Risk estimation is about situations, and risk evaluation about the effect on people. Few situations are absolutely safe. Risks need to be estimated, and for many kinds of risk (e.g., exposures to potentially toxic substances or to potentially catastrophic situations) an expert view has to be formed, which must take account of associated uncertainties. Different sections of the public perceive risk in different ways, and regard some risks more seriously than the expert estimates. Thus studies of risk perception form a further input into the decision-making process. Another input is the benefit of the activity. A regulatory framework consistent with the reality of risk estimation has been proposed. Since risks and benefits fall on different parts of the community, the decision process is essentially political, though it must be informed scientifically. How the decision is taken will depend on national governmental practices.     

芦山地震灾区次生山地灾害分布特征及其成因分析

选取芦山地震涉及的21个县（市、区）为研究对象,应用野外实地踏勘和遥感解译相结合的方法,结合当地国土、水利、建设等部门提供的相关统计资料,已查明芦山地震灾区782处次生山地灾害（滑坡、崩塌和泥石流）,获取了这些次生山地灾害的基础信息。在GIS信息技术的支持下,对芦山地震灾区次生山地灾害的发育环境背景、分布特征和成因进行了初步的探讨分析。研究表明：芦山地震灾区次生山地灾害主要集中分布在烈度为Ⅷ Ⅸ区、中低山区、坡度0°～40°、坡向为东西两向、第三系砂砾夹泥岩区、河流冲刷强烈和年降雨量＞1 200 mm的区域;发育成因主要是地形条件对次生山地灾害的形成的影响表现出与非地震条件下的新特征;地震效应重构了地表形态,为次生山地灾害发育提供了大量的松散固体物质;降水与河流冲刷作用的改变,影响边坡稳定性,为次生山地灾害提供动力;人类过度的社会经济活动加速了次生山地灾害的形成     

Assessing the human health impacts of exposure to disinfection by-products — A critical review of concepts and methods

Understanding the public health implications of chemical contamination of drinking water is important for societies and their decision-makers. The possible population health impacts associated with exposure to disinfection by-products (DBPs) are of particular interest due to their potential carcinogenicity and their widespread occurrence as a result of treatments employed to control waterborne infectious disease.We searched the literature for studies that have attempted quantitatively to assess population health impacts and health risks associated with exposure to DBPs in drinking water. We summarised and evaluated these assessments in terms of their objectives, methods, treatment of uncertainties, and interpretation and communication of results.In total we identified 40 studies matching our search criteria. The vast majority of studies presented estimates of generic cancer and non-cancer risks based on toxicological data and methods that were designed with regulatory, health-protective purposes in mind, and therefore presented imprecise and biased estimates of health impacts. Many studies insufficiently addressed the numerous challenges to DBP risk assessment, failing to evaluate the evidence for a causal relationship, not appropriately addressing the complex nature of DBP occurrence as a mixture of chemicals, not adequately characterising exposure in space and time, not defining specific health outcomes, not accounting for characteristics of target populations, and not balancing potential risks of DBPs against the health benefits related with drinking water disinfection. Uncertainties were often poorly explained or insufficiently accounted for, and important limitations of data and methods frequently not discussed. Grave conceptual and methodological limitations in study design, as well as erroneous use of available dose–response data, seriously impede the extent to which many of these assessments contribute to understanding the public health implications of exposure to DBPs. In some cases, assessment results may cause unwarranted alarm among the public and potentially lead to poor decisions being made in sourcing, treatment, and provision of drinking water. We recommend that the assessment of public health impacts of DBPs should be viewed as a means of answering real world policy questions relating to drinking water quality, including microbial contaminants; that they should be conducted using the most appropriate and up-to-date data and methods, and that associated uncertainties and limitations should be accounted for using quantitative methods where appropriate.     

Eco-material selection using fuzzy TOPSIS method

In the classical multiple attribute decision-making or MADM methods, the ratings and the weights of the criteria are known precisely. However, in eco-material selection exercises, the available data are typically inadequate because of the selection dual quantitative and qualitative natures. Some of the qualitative selection criteria can be rated in several classes rather being expressed by exact numerical values; hence the application of fuzzy concepts in decision-making seems attractive to deal with such kind of ratings. Thusly, the presented study attempts to propose an eco-material selection approach specific to the automobile body panels using a fuzzy technique for order preference by similarity to ideal solution (TOPSIS), to incorporate both numerical and rating-based criteria into one holistic sustainability model. TOPSIS and fuzzy logic can aid the material selection process in translating the design goals and parameters into usable numbers that in turn can be used to rank candidate materials in their closeness to the ideal solution. An additional uniqueness of this study stems from using the fuzzy-TOPSIS as a scoring tool without any assigned weights for the different selection attributes, in order to avoid the bias that is typically associated with other classical MADM, such as quality function deployment, analytical hierarchy process and digital logic.     

Carnivores in corridors: estimating tiger occupancy in Kanha–Pench corridor,Madhya Pradesh,India

Elderly people are known to be more vulnerable than the general population to a range of weather-related hazards such as heat waves, icy conditions and cold periods. In the Nordic region, some of these hazards are projected to change their frequency and intensity in the future, while at the same time strong increases are projected in the proportion of elderly in the population. This paper reports results from three projects studying the potential impacts of climate change on elderly people in the Nordic region. An interactive web-based tool has been developed for mapping and combining indicators of climate change vulnerability of the elderly, by municipality, across three Nordic countries: Finland, Norway and Sweden. The tool can also be used for projecting temperature-related mortality in Finland under different projections of future climate. The approach to vulnerability mapping differs from most previous studies in which researchers selected the indicators to combine into an index. Here, while researchers compile data on indicators that can be accessed in the mapping tool, the onus is on the users of the tool to decide which indicators are of interest and whether to map them individually or as combined indices. Stakeholders with responsibility for the care and welfare of the elderly were engaged in the study through interviews and a workshop. They affirmed the usefulness of the prototype mapping tool for raising awareness about climate change as a potential risk factor for the elderly and offered suggestions on potential refinements, which have now been implemented. These included adding background information on possible adaptation measures for ameliorating the impacts of extreme temperatures, and improved representation of uncertainties in projections of future exposure and adaptive capacity.     

Development of coastal recreational water quality standards in the Mediterranean

Concern about adverse health effects arising out of human exposure to polluted seawater through bathing and other forms of aquatic recreation has led to the development of various quality criteria and standards worldwide. Attempts at quantifying health hazards from polluted recreational waters have been made in several Mediterranean countries through the conduction of epidemiological studies aimed at establishing direct correlation between the microbiological quality of the water and health effects on exposed population groups. This article provides an overview on the development of the criteria and standards for coastal recreational waters in the Mediterranean by examining the evolution of the WHO guidelines, the WHO/UNEP interim criteria for bathing waters and the EU Directives. It also provides a brief account of the various quality criteria and standards for coastal recreational waters in current use in all the Mediterranean countries.     

An ethical dimension to sustainable restoration and long-term management of contaminated areas

Experience after the Chernobyl accident has shown that restoration strategies need to consider a wide range of different issues to ensure the long-term sustainability of large and varied contaminated areas. Thus, the criteria by which we evaluate countermeasures need to be extended from simple cost-benefit effectiveness and radiological protection standards to a more integrated, holistic approach, including social and ethical aspects. Within the STRATEGY project, the applicability of many countermeasures is being critically assessed using a wide range of criteria. Attention is being given to issues such as practicability, feasibility, capacity and environmental side-effects, as well as social factors such as public perceptions of risk, communication of information and the need for dialogue and consultation with affected communities, and ethical aspects such as informed consent and the fair distribution of costs and doses. Although such socio-ethical factors are now the subject of a substantial field of research, there has been little attempt to integrate them in a practical context for decision makers. Within this paper, we specifically consider the ethical aspects of restoration strategies and suggest practical means by which these can be taken into account in the decision making process, introducing a value matrix. The paper covers two critical areas: evaluation of individual countermeasures, and use of the matrix to ensure transparent and systematic consideration of values in selection of a restoration strategy.     

典型湖库富营养化的模糊综合评价研究

随着氮磷等营养盐类的不断排入湖库中,导致了水体的富营养化,使得水体透明度下降,产生异味,对人们的身体健康造成威胁。通过采用合适的水体富营养化评价模型,可以对水体的污染现状进行评价,得出正确的结论,以便采用适当的处理方式及时处理富营养化状况,减少对水环境和人体健康的危害。采用模糊综合评价法,将评价指标进行层次分析,并根据指标的相互关系,确定了各指标的权重,建立了模糊综合评价的数学模型。最终根据建立的评价指标体系、确定的评价标准和实测的湖库（巢湖、洱海和微山湖等）水质资料,得到了我国典型湖库的富营养化评价结论。评价结果与实际状况相吻合,说明该模型适合广泛应用     

跨界水资源公平合理利用原则的困境与对策

公平合理利用原则是国际水法的一项基本原则,它的内涵体现为权利义务的一致性,即各国有在其领土内利用跨界水资源的权利,同时又要承担不剥夺其他国家在其领土内利用跨界水资源的义务和不对跨界水资源进行损害和浪费的义务。从理论上看,对保护跨界水资源及协调跨界水资源利用冲突有重要的意义。但由于公平合理利用原则目前尚存在评价标准不明确、保障制度不完备等内在缺陷,以致其在实践中经常陷于难以适用的困境。要摆脱公平合理利用原则的适用困境,应以权利义务相一致的原理为指导,进一步明确“公平合理利用”的评价标准,厘清必要的用水优先权顺序,使公平合理利用原则具有可操作性。同时,应建立起受益补偿制度、公众参与制度、损害预警制度等有利于公平合理利用原则实现的保障制度。