Bad Reporting or Bad Science? Systematic Data Evaluation as a Means to Improve the Use of Peer-Reviewed Studies in Risk Assessments of Chemicals

In this study we assess the applicability of a set of reliability criteria proposed by Ågerstrand et al. This was done by evaluating the reliability of 12 non-standard peer-reviewed ecotoxicity and toxicity studies for Bisphenol A. There was an overall agreement between the evaluator and the authors of the papers regarding the result of the evaluations. This suggests that the criteria offer enough guidance to be a useful and consistent evaluation tool. It provides a transparent and structured approach, and ensures that a minimum and similar set of criteria is used. The evaluation of the peer-reviewed ecotoxicity and toxicity studies concludes that important information is sometimes missing, and therefore the studies do not always meet common regulatory requirements regarding reporting. Whether this is due to insufficient reporting or due to poorly performed studies is not known. To improve the reporting, and thereby promote reliability and reproducibility, researchers, reviewers, and editors are recommended to use the suggested criteria as a guideline. In conclusion, in order to improve the reliability of peer-reviewed studies, and to increase their use in regulatory risk assessments of chemicals, the dialog between regulators, researchers, and editors regarding how to evaluate and report studies needs to be strengthened.     

Initial Risk-Based Screening of Potential Brownfield Development Sites

Brownfield redevelopment is sustainable only when it is a transparent process protective of public health. The objective of the brownfield health risk screening matrix is to provide a scientifically based, transparent process to evaluate human health risks on proposed redevelopment sites as well as a framework that can be critically evaluated by both environmentalists and the community in general. Public discussion and understanding of current health risk assessment, as well as the risks specific to each brownfield redevelopment site, are essential for an effective brownfield redevelopment program.

The Brownfields Redevelopment Program was started by the EPA in 1995 and seeks to use already contaminated sites rather than contaminate even more greenfields. Two of the biggest difficulties are making redevelopment profitable and protecting human health. Traditional human health risk assessment evaluates single chemical exposures and identifies the level below which no adverse effect will occur to the most sensitive subgroups of the population. For cancer–causing chemicals the risk must be lower than 1:1,000,000. When brownfield redevelopment sites are associated with high cost, extensive time and unmanageable uncertainty, additional greenfield sites will become contaminated and the contamination on current brownfield sites will remain un-remediated.

The citizens' advisory group addressing brownfields in a southern New York county has developed a risk matrix to evaluate the uncertainty of the available data, the toxicity of the known or suspected contaminants and the likely exposure routes for each brownfield site in the county. The matrix categorizes sites as high, medium or low risk according to exposure groups. The risk matrix complements the triad approach currently being developed by EPA to identify and manage project decision uncertainties, addresses uncertainty as well as toxicity and has the potential to reduce the cost of traditional health risk assessment at brownfield redevelopment sites.     

Multidisciplinary European Low Dose Initiative (MELODI): strategic research agenda for low dose radiation risk research

MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website (http://www.melodi-online.eu/sra.html).     

Ecotoxicity evaluation of PFBSK for the whole environmental compartments and comprehensive comparison of hazard and risk to PFOS

A series of perfluorobutane sulfonate (PFBS)-related substances are produced as the alternatives to corresponding perfluorooctane sulfonate (PFOS). However, there is little reliable information about PFBS available for the whole ecotoxicology compartments. At present, its ecotoxicity of perfluorobutane sulfonate potassium (PFBSK) was selected as a typical PFBS chemical to investigate and evaluate its aquatic, terrestrial, microorganism and sediment toxicity according to the Organization for Economic Cooperation and Development (OECD) guideline under the framework of the REACH regulation. Meanwhile, the ecotoxicology hazard and risk for PFBSK and PFOS were compared comprehensively.

PFBSK did not show acute and chronic aquatic, microorganisms and terrestrial animal toxicity, while exhibited some terrestrial plants toxicity. The ecotoxicology of PFBSK decreased sharply except for terrestrial plants compared with PFOS. Especially, for acute and chronic aquatic ecotoxicity, PFBSK is lower than 100 times those of PFOS.

Although the similar terrestrial plants toxicity level was observed for PFBSK and PFOS, the lower risk of PFBSK was deduced for the reason that there was far less chances to be exposed and retained in the soil and sediment for its high water solubility and low adsorption.

In conclusion, PFBSK showed lower ecotoxicity hazard and risk than those of PFOS. PFBSK could be an environmental friendly alternative to PFOS.     

Potential use of an arthropod database to support the non-target risk assessment and monitoring of transgenic plants

Worldwide, plants obtained through genetic modification are subject to a risk analysis and regulatory approval before they can enter the market. An area of concern addressed in environmental risk assessments is the potential of genetically modified (GM) plants to adversely affect non-target arthropods and the valued ecosystem services they provide. Environmental risk assessments are conducted case-by-case for each GM plant taking into account the plant species, its trait(s), the receiving environments into which the GM plant is to be released and its intended uses, and the combination of these characteristics. To facilitate the non-target risk assessment of GM plants, information on arthropods found in relevant agro-ecosystems in Europe has been compiled in a publicly available database of bio-ecological information during a project commissioned by the European Food Safety Authority (EFSA). Using different hypothetical GM maize case studies, we demonstrate how the information contained in the database can assist in identifying valued species that may be at risk and in selecting suitable species for laboratory testing, higher-tier studies, as well as post-market environmental monitoring.     

Improving structure and transparency in reliability evaluations of data under REACH: suggestions for a systematic method

Abstract

The goal of identifying hazardous chemicals registered under the Registration, Evaluation, Authorization and restriction of CHemicals (REACH) Regulation and taking appropriate risk management measures relies on robust data registrations. However, the current procedures for European chemical manufacturers and importers to evaluate data under REACH neither support systematic evaluations of data nor transparently communicate these assessments. The aim of this study was to explore how using a data evaluation method with predefined criteria for reliability and establishing principles for assigning reliability categories could contribute to more structured and transparent evaluations under REACH. In total, 20 peer-reviewed studies for 15 substances registered under REACH were selected for an in-depth evaluation of reliability with the SciRAP tool. The results show that using a method for study evaluation, with clear criteria for assessing reliability and assigning studies to reliability categories, contributes to more structured and transparent reliability evaluations. Consequently, it is recommended to implement a method for evaluating data under REACH with predefined criteria and fields for documenting and justifying the assessments to increase consistency of data evaluations and transparency.     

Genomic Target Database (GTD): A database of potential targets in human pathogenic bacteria

A Genomic Target Database (GTD) has been developed having putative genomic drug targets for human bacterial pathogens. The selected pathogens are either drug resistant or vaccines are yet to be developed against them. The drug targets have been identified using subtractive genomics approaches and these are subsequently classified into

1. Drug targets in pathogen specific unique metabolic pathways,
2. Drug targets in host-pathogen common metabolic pathways, and
3. Membrane localized drug targets.

HTML code is used to link each target to its various properties and other available public resources. Essential resources and tools for subtractive genomic analysis, sub-cellular localization, vaccine and drug designing are also mentioned. To the best of authors knowledge, no such database (DB) is presently available that has listed metabolic pathways and membrane specific genomic drug targets based on subtractive genomics. Listed targets in GTD are readily available resource in developing drug and vaccine against the respective pathogen, its subtypes, and other family members. Currently GTD contains 58 drug targets for four pathogens. Shortly, drug targets for six more pathogens will be listed.

Availability

GTD is available at IIOAB website http://www.iioab.webs.com/GTD.htm. It can also be accessed at http://www.iioabdgd.webs.com.GTD is free for academic research and non-commercial use only. Commercial use is strictly prohibited without prior permission from IIOAB.     

Soil ingestion estimates for use in site evaluations based on the best tracer method

This paper develops a novel methodology, the Best Tracer method (BTM), that substantially overcomes the principal limitations (intertracer inconsistencies, and poor precision of recovery) of estimating soil ingestion by specific soil‐based tracers in massbalance studies. The BTM incorporates a biological and statistical framework that improves precision of recovery of tracer estimates, markedly reducing input‐output misalignment error resulting from a lack of correspondence between food tracer input and fecal tracer output.

This method is then used to re‐estimate the soil ingestion distribution of previously published soil ingestion estimates from two children studies (Calabrese et al. 1989; Davis et al., 1990) and one adult study (Calabrese et al., 1990). Revised estimates of soil ingestion are provided for each study. In addition, the results from the two children's studies are combined to form a single estimate of the soil ingestion distribution. These collective findings result in more reliable quantitative estimates of soil ingestion than trace element specific estimates, as well as providing improved understanding of current published soil ingestion studies, and improved methods that will enhance the design and interpretation of future soil ingestion studies.

With respect to children, the data indicate that the Calabrese et al. (1989) study provides the most reliable estimates of soil ingestion based on the estimated precision of recovery. However, estimates for the combined data of the Calabrese et al. (1989) and Davis et al. (1990) studies include all available children's data from mass balance studies, and thus provide more robust estimates. The collective data suggest that the median child in these studies ingested 30–40 mg/day of soil, while the upper 95% estimate is approximately 200 mg/day. Current data are insufficient to distinguish the children's soil ingestion distribution from that of adults. The revised and improved estimates of soil ingestion for children and adults have important implications for contaminant exposure estimates used in site evaluation risk assessment procedures.     

In Defense of Risk Assessment: A Reply to the Environmental Justice Movement's Critique

The environmental justice movement believes risk assessment is undemocratic. The movement believes risk assessment is a way of trading human health for profit and a means of legitimizing exposure to toxic chemicals. The movement considers risk assessment an evil industry and a tool developed by those who wish to oppress racial and ethnic minorities. These beliefs are wrong and the environmental justice movement is a Luddite enterprise. Risk assessment is a fundamentally democratic process and enables all people, regardless of race, ethnicity, income or social status, to enjoy the benefits of technology and also suffer its drawbacks within a framework of equality and democracy. “A savage servility slides by on grease.” -Robert Penn Warren For the Union Dead

     

Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project

Two large-scale phenotyping efforts, the European Mouse Disease Clinic (EUMODIC) and the Wellcome Trust Sanger Institute Mouse Genetics Project (SANGER-MGP), started during the late 2000s with the aim to deliver a comprehensive assessment of phenotypes or to screen for robust indicators of diseases in mouse mutants. They both took advantage of available mouse mutant lines but predominantly of the embryonic stem (ES) cells resources derived from the European Conditional Mouse Mutagenesis programme (EUCOMM) and the Knockout Mouse Project (KOMP) to produce and study 799 mouse models that were systematically analysed with a comprehensive set of physiological and behavioural paradigms. They captured more than 400 variables and an additional panel of metadata describing the conditions of the tests. All the data are now available through EuroPhenome database (www.europhenome.org) and the WTSI mouse portal (http://www.sanger.ac.uk/mouseportal/), and the corresponding mouse lines are available through the European Mouse Mutant Archive (EMMA), the International Knockout Mouse Consortium (IKMC), or the Knockout Mouse Project (KOMP) Repository. Overall conclusions from both studies converged, with at least one phenotype scored in at least 80?% of the mutant lines. In addition, 57?% of the lines were viable, 13?% subviable, 30?% embryonic lethal, and 7?% displayed fertility impairments. These efforts provide an important underpinning for a future global programme that will undertake the complete functional annotation of the mammalian genome in the mouse model.     

Contextual Cross-Referencing of Species Names for Fiddler Crabs (Genus Uca): An Experiment in Cyber-Taxonomy

Cyber-taxonomy of name usage has focused primarily on producing authoritative lists of names or cross-linking names and data across disparate databases. A feature missing from much of this work is the recording and analysis of the context in which a name was used—context which can be critical for understanding not only what name an author used, but to which currently recognized species they actually refer. An experiment on recording contextual information associated with name usage was conducted for the fiddler crabs (genus Uca). Data from approximately one quarter of all publications that mention fiddler crabs, including 95% of those published prior to 1924 and 67% of those published prior to 1976, have currently been recorded in a database. Approaches and difficulties in recording and analyzing the context of name use are discussed. These results are not meant to be a full solution, rather to highlight problems which have not been previously investigated and may act as a springboard for broader approaches and discussion. Some data on the accessibility of the literature, including in particular electronic forms of publication, are also presented. The resulting data has been integrated for general browsing into the website http://www.fiddlercrab.info; the raw data and code used to construct the website is available at https://github.com/msrosenberg/fiddlercrab.info.     

Cost-Effectiveness of Interventions to Prevent Disability in Leprosy: A Systematic Review

Background

Prevention of disability (POD) is one of the key objectives of leprosy programmes. Recently, coverage and access have been identified as the priority issues in POD. Assessing the cost-effectiveness of POD interventions is highly relevant to understanding the barriers and opportunities to achieving universal coverage and access with limited resources. The purpose of this study was to systematically review the quality of existing cost-effectiveness evidence and discuss implications for future research and strategies to prevent disability in leprosy and other disabling conditions.

Methodology/Principal Findings

We searched electronic databases (NHS EED, MEDLINE, EMBASE, and LILACS) and databases of ongoing trials (www.controlled-trials.com/mrct/, www.who.int/trialsearch). We checked reference lists and contacted experts for further relevant studies. We included studies that reported both cost and effectiveness outcomes of two or more alternative interventions to prevent disability in leprosy. We assessed the quality of the identified studies using a standard checklist for critical appraisal of economic evaluations of health care programmes. We found 66 citations to potentially relevant studies and three met our criteria. Two were randomised controlled trials (footwear, management of neuritis) and one was a generic model-based study (cost per DALY). Generally, the studies were small in size, reported inadequately all relevant costs, uncertainties in estimates, and issues of concern and were based on limited data sources. No cost-effectiveness data on self-care, which is a key strategy in POD, was found.

Conclusion/Significance

Evidence for cost-effectiveness of POD interventions for leprosy is scarce. High quality research is needed to identify POD interventions that offer value for money where resources are very scarce, and to develop strategies aimed at available, affordable and sustainable quality POD services for leprosy. The findings are relevant for other chronically disabling conditions, such as lymphatic filariasis, Buruli ulcer and diabetes in developing countries.     

Evaluating Human and Ecological Impacts of a Product Life Cycle: The Complementary Roles of Life-Cycle Assessment and Risk Assessment

Life-cycle assessment (LCA) is a tool for evaluating various health and environmental impacts throughout a product's life. When used as a screening tool, LCA can potentially identify the processes and materials most likely to pose a threat to human health and the environment, and to determine where a risk assessment is warranted. The European Union has issued a ban on lead-based solder from use in electronic equipment beginning in July 2006. In response, the Lead-Free Solder Partnership, involving the U.S. Environmental Protection Agency, several electronics manufacturers, and the University of Tennessee afforded a vehicle for conducting a thorough LCA of leaded and lead-free solders used in the electronics industry. Sixteen impact categories were evaluated in the LCA, including human toxicity.

A primary conclusion of the assessment for human and aquatic toxicity, across the entire life cycle of tin-lead solder, was the potential for impacts derived from the landfilling of lead. These results, based on broad assumptions about exposure, suggest that a more detailed risk assessment of the landfilling process would assist in better understanding the potential for health and environmental risks. We believe LCA data can be used to identify the need for focused risk assessments, allowing the two tools to effectively complement one another. Use of both methods could assist in understanding the effectiveness of the European ban on lead solder and its potential to improve public health.     

Estimating the hazard of chemical substances to aquatic life

The assessment of the hazard associated with the introduction of chemical substances into the environment is receiving considerable attention in current ecological, political, and public forums. The purpose of this paper is to identify and evaluate the basic concepts involved in assessing the hazard of chemical substances to aquatic life. A conceptual framework for conducting a hazard assessment is elaborated. In addition, several proposed procedures for conducting aquatic hazard assessment are compared and contrasted. A discussion of the decision criteria currently utilized in hazard assessment procedures is included. The use of safety factors or uncertainty factors as a central concept in a sequential testing approach is presented. An assessment of the state-of-the-art in aquatic hazard assessment and recommendations for suceeding stpes in the development of procedures constitute the conclusion of the paper.     

The Development of the Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS): A Large-Scale Data Sharing Initiative

Introduction

In 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons’ health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative (www.topics-mds.eu).

Materials and Methods

A working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden).

Results

Between 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies.

Discussion

TOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus supporting the feasibility of constructing a large (>30,000 observations), standardised dataset pooled from various study protocols with different sampling frameworks. This unique implementation strategy improves efficiency and facilitates individual-level data meta-analysis.     

Regulatory Mode and Risk-Taking: The Mediating Role of Anticipated Regret

We propose that decision maker’s regulatory mode affects risk-taking through anticipated regret. In the Study 1 either a locomotion or an assessment orientation were experimentally induced, and in the Studies 2 and 3 these different orientations were assessed as chronic individual differences. To assess risk-taking we used two behavioral measures of risk: BART and hot-CCT. The results show that experimentally induced assessment orientation–compared to locomotion–leads to decreased risk-taking through increased anticipated regret (Study 1). People chronically predisposed to be in the assessment state take less risk through increased anticipated regret (Study 2 and Study 3). Study 2 results also show a marginally non-significant indirect effect of chronic locomotion mode on BART through anticipated regret. Differently, Study 3 shows that people chronically predisposed to be in the locomotion state take greater risk through decreased anticipated regret, when play a dynamic risk task triggering stronger emotional arousal. Through all three studies, the average effect size for the relationship of assessment with anticipated regret was in the moderate-large range, whereas for risk-taking was in the moderate range. The average effect size for the relationship of locomotion with anticipated regret was in the moderate range, whereas for risk-taking was in the small-moderate range. These results increase our understanding of human behavior under conditions of risk obtaining novel insights into regulatory mode theory and decision science.     

Circulating microparticles in cardiovascular disease: going on stage!

Context: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. In spite of the fact that treatments are based on risk calculators which in turn are based on population characteristics, it is well known that these methods have definite levels of uncertainty. Recently, more precise diagnostic or predictive methods have been developed based on indicators of vascular and/or cardiac damage in order to supplement this risk evaluation.

Objective: In this review, we describe the main discoveries leading to the idea of using circulating microparticles as a promising and complementary tool in the evaluation of cardiovascular risk.

Methods: A Medline search for the terms cardiovascular diseases, microparticles, miRNAs, diagnosis, prognosis, biomarkers and microvesicles was performed.

Results: We found (i) nine articles, which were relevant to forming the idea of using microparticles as biomarkers in CVDs, and (ii) 15 and 12 experimental clinical studies which describe their potential in primary and secondary CVD prevention, respectively.

Conclusions: The levels of circulating microparticles have been associated with cardiovascular damage in asymptomatic patients as well as in patients who suffered a cardiovascular event, becoming promising diagnostics or prediction biomarkers in recent years.     

Brazilian genetic database of chromosome X

The X chromosome is a singular source of information in population genetics, anthropological research and in forensic cases. Thus, many researchers have been interested in characterizing X chromosome markers in different populations. The Brazilian Genetic Database of Chromosome X (BGBX—Banco Genético Brasileiro do Cromossomo X) website is freely available in Portuguese and English versions and was developed with the main purpose of compiling all Brazilian population genetic data for X chromosome short tandem repeats (X-STRs) markers published in scientific journals searchable via PubMed. Furthermore, this database presents other relevant information concerning X-STRs, such as genetic and physical locations, allele structure, nomenclature, mutation rates, primers described in the literature and likelihood ratio calculation. The entire scientific community is now encouraged to submit their X-STR population genetic data to this website, available at http://www.bgbx.com.br. Regarding future prospects of BGBX, the authors intend to expand the website with data and information of X-linked insertion–deletion polymorphisms.