Integrated presentation of ecological risk from multiple stressors

PubMed Central

Goussen, Benoit; Price, Oliver R.; Rendal, Cecilie; Ashauer, Roman

2016-01-01

Current environmental risk assessments (ERA) do not account explicitly for ecological factors (e.g. species composition, temperature or food availability) and multiple stressors. Assessing mixtures of chemical and ecological stressors is needed as well as accounting for variability in environmental conditions and uncertainty of data and models. Here we propose a novel probabilistic ERA framework to overcome these limitations, which focusses on visualising assessment outcomes by construct-ing and interpreting prevalence plots as a quantitative prediction of risk. Key components include environmental scenarios that integrate exposure and ecology, and ecological modelling of relevant endpoints to assess the effect of a combination of stressors. Our illustrative results demonstrate the importance of regional differences in environmental conditions and the confounding interactions of stressors. Using this framework and prevalence plots provides a risk-based approach that combines risk assessment and risk management in a meaningful way and presents a truly mechanistic alternative to the threshold approach. Even whilst research continues to improve the underlying models and data, regulators and decision makers can already use the framework and prevalence plots. The integration of multiple stressors, environmental conditions and variability makes ERA more relevant and realistic. PMID:27782171

Assessing the relevance of ecotoxicological studies for regulatory decision making.

PubMed

Rudén, Christina; Adams, Julie; Ågerstrand, Marlene; Brock, Theo Cm; Poulsen, Veronique; Schlekat, Christian E; Wheeler, James R; Henry, Tala R

2017-07-01

Regulatory policies in many parts of the world recognize either the utility of or the mandate that all available studies be considered in environmental or ecological hazard and risk assessment (ERA) of chemicals, including studies from the peer-reviewed literature. Consequently, a vast array of different studies and data types need to be considered. The first steps in the evaluation process involve determining whether the study is relevant to the ERA and sufficiently reliable. Relevance evaluation is typically performed using existing guidance but involves application of "expert judgment" by risk assessors. In the present paper, we review published guidance for relevance evaluation and, on the basis of the practical experience within the group of authors, we identify additional aspects and further develop already proposed aspects that should be considered when conducting a relevance assessment for ecotoxicological studies. From a regulatory point of view, the overarching key aspect of relevance concerns the ability to directly or indirectly use the study in ERA with the purpose of addressing specific protection goals and ultimately regulatory decision making. Because ERA schemes are based on the appropriate linking of exposure and effect estimates, important features of ecotoxicological studies relate to exposure relevance and biological relevance. Exposure relevance addresses the representativeness of the test substance, environmental exposure media, and exposure regime. Biological relevance deals with the environmental significance of the test organism and the endpoints selected, the ecological realism of the test conditions simulated in the study, as well as a mechanistic link of treatment-related effects for endpoints to the protection goal identified in the ERA. In addition, uncertainties associated with relevance should be considered in the assessment. A systematic and transparent assessment of relevance is needed for regulatory decision making. The relevance aspects also need to be considered by scientists when designing, performing, and reporting ecotoxicological studies to facilitate their use in ERA. Integr Environ Assess Manag 2017;13:652-663. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2016 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Feeding Behavior of an Aquatic Snail as a Simple Endpoint to Assess the Exposure to Cadmium.

PubMed

Alonso, Álvaro; Valle-Torres, Guillermo

2018-01-01

One of the aims of ecotoxicology is the assessment of the effects of chemicals on the ecosystems. Bioassays assessing lethality are frequently used in ecotoxicology, however they usually employ supra-environmental toxic concentrations. Toxicity tests employing behavioral endpoints may present a balance between simplicity (i.e., laboratory bioassays) and complexity (i.e., relevant ecological effects). The aim of this study was to develop a feeding behavioral bioassay with the aquatic snail, Potamopyrgus antipodarum, which included a 2 days exposure to cadmium, followed by a 9 days post-exposure observational period. Several behavioral feeding endpoints were monitored, including percentage of actively feeding animals, percentage of animals in food quadrants and a mobility index. The percentage of actively feeding animals was reduced by the four cadmium treatments (0.009, 0.026, 0.091 and 0.230 mg Cd/L) with the stronger effect in the highest concentration. The two highest cadmium concentrations significantly reduced the percentage of animals in food quadrants and the mobility index. Therefore, the percentage of actively feeding animals was the most sensitive endpoint to cadmium toxicity as the four cadmium concentrations caused a significant decrease in this endpoint. It is concluded that feeding behavior is a useful endpoint to detect the exposure of aquatic snails to cadmium.

Dredging Research: Information from the Engineer Research and Development Center. Volume 7, Number 1. Corps Education Center a Big Success

DTIC Science & Technology

2004-03-01

likeli- hood of adverse effects. UDMEED contains ecotoxico - logical and reference data relevant to assessing the potential for impacts of concern...The effects data have been translated into ecotoxico - logical endpoints, such as “No Observed Adverse Ecological Effect Level (NOAEL),” “Lethal...ited in an upland situation, several broad taxonomic categories, and various contaminants (e.g., bio- accumulation and plants and metals ; or toxicity

Complexity of bioindicator selection for ecological, human, and cultural health: Chinook salmon and red knot as case studies

PubMed Central

Burger, Joanna; Gochfeld, Michael; Niles, Lawrence; Powers, Charles; Brown, Kevin; Clarke, James; Dey, Amanda; Kosson, David

2015-01-01

There is considerable interest in developing bioindicators of ecological health that are also useful indicators for human health. Yet, human health assessment usually encompasses physical/chemical exposures and not cultural well-being. In this paper, we propose that bioindicators can be selected for all three purposes. We use Chinook or king salmon (Oncorhynchus tshawytscha) and red knot (Calidris canutus rufa, a sandpiper) as examples of indicators that can be used to assess human, ecological, and cultural health. Even so, selecting endpoints or metrics for each indicator species is complex and is explored in this paper. We suggest that there are several endpoint types to examine for a given species, including physical environment, environmental stressors, habitat, life history, demography, population counts, and cultural/societal aspects. Usually cultural endpoints are economic indicators (e.g., number of days fished, number of hunting licenses), rather than the importance of a fishing culture. Development of cultural/societal endpoints must include the perceptions of local communities, cultural groups, and tribal nations, as well as governmental and regulatory communities (although not usually so defined, the latter have cultures as well). Endpoint selection in this category is difficult because the underlying issues need to be identified and used to develop endpoints that tribes and stakeholders themselves see as reasonable surrogates of the qualities they value. We describe several endpoints for salmon and knots that can be used for ecological, human, and cultural/societal health. PMID:25666646

Complexity of bioindicator selection for ecological, human, and cultural health: Chinook salmon and red knot as case studies

DOE PAGES

Burger, Joanna; Gochfeld, Michael; Niles, Lawrence; ...

2015-02-10

There is considerable interest in developing bioindicators of ecological health that are also useful indicators for human health. Yet, human health assessment usually encompasses physical/chemical exposures and not cultural well-being. In this paper, we propose that bioindicators can be selected for all three purposes. We use Chinook or king salmon (Oncorhynchus tshawytscha) and red knot (Calidris canutus rufa, a sandpiper) as examples of indicators that can be used to assess human, ecological, and cultural health. Even so, selecting endpoints or metrics for each indicator species is complex and is explored in this paper. Here, we suggest that there are severalmore » endpoint types to examine for a given species, including physical environment, environmental stressors, habitat, life history, demography, population counts, and cultural/societal aspects. Usually cultural endpoints are economic indicators (e.g., number of days fished, number of hunting licenses), rather than the importance of a fishing culture. Development of cultural/societal endpoints must include the perceptions of local communities, cultural groups, and tribal nations, as well as governmental and regulatory communities (although not usually so defined, the latter have cultures as well). Endpoint selection in this category is difficult because the underlying issues need to be identified and used to develop endpoints that tribes and stakeholders themselves see as reasonable surrogates of the qualities they value. We describe several endpoints for salmon and knots that can be used for ecological, human, and cultural/societal health.« less

Complexity of bioindicator selection for ecological, human, and cultural health: Chinook salmon and red knot as case studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burger, Joanna; Gochfeld, Michael; Niles, Lawrence

There is considerable interest in developing bioindicators of ecological health that are also useful indicators for human health. Yet, human health assessment usually encompasses physical/chemical exposures and not cultural well-being. In this paper, we propose that bioindicators can be selected for all three purposes. We use Chinook or king salmon (Oncorhynchus tshawytscha) and red knot (Calidris canutus rufa, a sandpiper) as examples of indicators that can be used to assess human, ecological, and cultural health. Even so, selecting endpoints or metrics for each indicator species is complex and is explored in this paper. Here, we suggest that there are severalmore » endpoint types to examine for a given species, including physical environment, environmental stressors, habitat, life history, demography, population counts, and cultural/societal aspects. Usually cultural endpoints are economic indicators (e.g., number of days fished, number of hunting licenses), rather than the importance of a fishing culture. Development of cultural/societal endpoints must include the perceptions of local communities, cultural groups, and tribal nations, as well as governmental and regulatory communities (although not usually so defined, the latter have cultures as well). Endpoint selection in this category is difficult because the underlying issues need to be identified and used to develop endpoints that tribes and stakeholders themselves see as reasonable surrogates of the qualities they value. We describe several endpoints for salmon and knots that can be used for ecological, human, and cultural/societal health.« less

USE OF SCALE INVARIANCE IN EVALUATING JUDGEMENT INDICATORS

EPA Science Inventory

Indicators are used to draw conclusions about ecological endpoints when these endpoints cannot be measured directly. In many cases, inference about an endpoint are only possible because assumptions have been made about the relationship between indicator and endpoint; we refer to ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

R. L. VanHorn; N. L. Hampton; R. C. Morris

This document presents reference material for conducting screening level ecological risk assessments (SLERAs)for the waste area groups (WAGs) at the Idaho National Engineering Laboratory. Included in this document are discussions of the objectives of and processes for conducting SLERAs. The Environmental Protection Agency ecological risk assessment framework is closely followed. Guidance for site characterization, stressor characterization, ecological effects, pathways of contaminant migration, the conceptual site model, assessment endpoints, measurement endpoints, analysis guidance, and risk characterization are included.

In situ microbiota distinguished primary anthropogenic stressor in freshwater sediments.

PubMed

Xie, Yuwei; Floehr, Tilman; Zhang, Xiaowei; Xiao, Hongxia; Yang, Jianghua; Xia, Pu; Burton, G Allen; Hollert, Henner

2018-08-01

Conventional assessment and evaluation of sediment quality are based on laboratory-based ecotoxicological and chemical measurements with lack of concern for ecological relevance. Microbiotas in sediment are responsive to pollutants and can be used as alternative ecological indicators of sediment pollutants; however, the linkage between the microbial ecology and ecotoxicological endpoints in response to sediment contamination has been poorly evaluated. Here, in situ microbiotas from the Three Gorges Reservoir (TGR) area of the Yangtze River were characterized by DNA metabarcoding approaches, and then, changes of in situ microbiotas were compared with the ecotoxicological endpoint, aryl hydrocarbon receptor (AhR) mediated activity, and level of polycyclic aromatic hydrocarbons (PAHs) in sediments. PAHs and organic pollutant mixtures mediating AhR activity had different effects on the structures of microbiotas. Specifically, Shannon indices of protistan communities were negatively correlated with the levels of AhR mediated activity and PAHs. The sediment AhR activity was positively correlated with the relative abundance of prokaryotic Acetobacteraceae, but had a negative correlation with protistan Oxytrichidae. Furthermore, a quantitative classification model was built to predict the level of AhR activity based on the relative abundances of Acetobacteraceae and Oxytrichidae. These results suggested that in situ Protista communities could provide a useful tool for monitoring and assessing ecological stressors. The observed responses of microbial community provided supplementary evidence to support that the AhR-active pollutants, such as PAHs, were the primary stressors of the aquatic community in TGR area. Copyright © 2018 Elsevier Ltd. All rights reserved.

ECOLOGICAL ENDPOINT MODELING FOR TMDLS: EFFECTS OF SEDIMENT ON FISH POPULATIONS

EPA Science Inventory

Sediment is one of the primary stressors of concern for Total Maximum Daily Loads (TMDLs) for streams, and often it is a concern because of its impact on ecological endpoints. A modeling approach relating sediment to stream fish population dynamics is presented. Equations are d...

Ecological risk assessment of bisphenol A in surface waters of China based on both traditional and reproductive endpoints.

PubMed

Guo, Lei; Li, Zhengyan; Gao, Pei; Hu, Hong; Gibson, Mark

2015-11-01

Bisphenol A (BPA) occurs widely in natural waters with both traditional and reproductive toxicity to various aquatic species. The water quality criteria (WQC), however, have not been established in China, which hinders the ecological risk assessment for the pollutant. This study therefore aims to derive the water quality criteria for BPA based on both acute and chronic toxicity endpoints and to assess the ecological risk in surface waters of China. A total of 15 acute toxicity values tested with aquatic species resident in China were found in published literature, which were simulated with the species sensitivity distribution (SSD) model for the derivation of criterion maximum concentration (CMC). 18 chronic toxicity values with traditional endpoints were simulated for the derivation of traditional criterion continuous concentration (CCC) and 12 chronic toxicity values with reproductive endpoints were for reproductive CCC. Based on the derived WQC, the ecological risk of BPA in surface waters of China was assessed with risk quotient (RQ) method. The results showed that the CMC, traditional CCC and reproductive CCC were 1518μgL(-1), 2.19μgL(-1) and 0.86μgL(-1), respectively. The acute risk of BPA was negligible with RQ values much lower than 0.1. The chronic risk was however much higher with RQ values of between 0.01-3.76 and 0.03-9.57 based on traditional and reproductive CCC, respectively. The chronic RQ values on reproductive endpoints were about threefold as high as those on traditional endpoints, indicating that ecological risk assessment based on traditional effects may not guarantee the safety of aquatic biota. Copyright © 2015 Elsevier Ltd. All rights reserved.

Individuals versus organisms versus populations in the definition of ecological assessment endpoints.

PubMed

Suter, Glenn W; Norton, Susan B; Fairbrother, Anne

2005-11-01

Discussions and applications of the policies and practices of the U.S. Environmental Protection Agency (USEPA) in ecological risk assessment will benefit from continued clarification of the concepts of assessment endpoints and of levels of biological organization. First, assessment endpoint entities and attributes can be defined at different levels of organization. Hence, an organism-level attribute, such as growth or survival, can be applied collectively to a population-level entity such as the brook trout in a stream. Second, assessment endpoints for ecological risk assessment are often mistakenly described as "individual level," which leads to the idea that such assessments are intended to protect individuals. Finally, populations play a more important role in risk assessments than is generally recognized. Organism-level attributes are used primarily for population-level assessments. In addition, the USEPA and other agencies already are basing management decisions on population or community entities and attributes such as production of fisheries, abundance of migratory bird populations, and aquatic community composition.

The multiple stressor ecological risk assessment for the mercury-contaminated South River and upper Shenandoah River using the Bayesian network-relative risk model.

PubMed

Landis, Wayne G; Ayre, Kimberley K; Johns, Annie F; Summers, Heather M; Stinson, Jonah; Harris, Meagan J; Herring, Carlie E; Markiewicz, April J

2017-01-01

We have conducted a regional scale risk assessment using the Bayesian Network Relative Risk Model (BN-RRM) to calculate the ecological risks to the South River and upper Shenandoah River study area. Four biological endpoints (smallmouth bass, white sucker, Belted Kingfisher, and Carolina Wren) and 4 abiotic endpoints (Fishing River Use, Swimming River Use, Boating River Use, and Water Quality Standards) were included in this risk assessment, based on stakeholder input. Although mercury (Hg) contamination was the original impetus for the site being remediated, other chemical and physical stressors were evaluated. There were 3 primary conclusions from the BN-RRM results. First, risk varies according to location, type and quality of habitat, and exposure to stressors within the landscape. The patterns of risk can be evaluated with reasonable certitude. Second, overall risk to abiotic endpoints was greater than overall risk to biotic endpoints. By including both biotic and abiotic endpoints, we are able to compare risk to endpoints that represent a wide range of stakeholder values. Third, whereas Hg reduction is the regulatory priority for the South River, Hg is not the only stressor driving risk to the endpoints. Ecological and habitat stressors contribute risk to the endpoints and should be considered when managing this site. This research provides the foundation for evaluating the risks of multiple stressors of the South River to a variety of endpoints. From this foundation, tools for the evaluation of management options and an adaptive management tools have been forged. Integr Environ Assess Manag 2017;13:85-99. © 2016 SETAC. © 2016 SETAC.

Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida.

PubMed

Jager, Tjalling; Crommentuijn, Trudie; van Gestel, Cornelis A M; Kooijman, Sebastiaan A L M

2007-01-01

Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level.

Biomarkers and surrogate endpoints in glaucoma clinical trials

PubMed Central

Medeiros, Felipe A

2015-01-01

Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies. PMID:25034049

Derivation of predicted no-effect concentration and ecological risk for atrazine better based on reproductive fitness.

PubMed

Zheng, Lei; Zhang, Yizhang; Yan, Zhenguang; Zhang, Juan; Li, Linlin; Zhu, Yan; Zhang, Yahui; Zheng, Xin; Wu, Jiangyue; Liu, Zhengtao

2017-08-01

Atrazine (ATZ) is an herbicide most commonly used in China and other regions of the world. It is reported toxic to aquatic organisms, and frequently occurs at relatively high concentrations. Currently, ATZ has been proved to affect reproduction of aquatic species at much lower levels. So it is controversial to perform ecological risk assessment using predicted no-effect concentrations (PENCs) derived from traditional endpoints, which fail to provide adequate protection to aquatic organisms. In this study, PNECs of ATZ were derived based on six endpoints of survival, growth, behavior, biochemistry, genetics and reproduction. The PNEC derived from reproductive lesion was 0.044μg ATZ L -1 , which was obviously lower than that derived from other endpoints. In addition, a tiered ecological risk assessment was conducted in the Taizi River based on six PNECs derived from six categories of toxicity endpoints. Results of these two methods of ecological risk assessment were consistent with each other, and the risk level of ATZ to aquatic organisms reached highest as taking reproductive fitness into account. The joint probability indicated that severe ecological risk rooting in reproduction might exist 93.9% and 99.9% of surface water in the Taizi River, while 5% threshold (HC 5 ) and 1% threshold (HC 1 ) were set up to protect aquatic organisms, respectively. We hope the present work could provide valuable information to manage and control ATZ pollution. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrating ecological risk assessments across levels of organization using the Franklin-Noss model of biodiversity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brugger, K.E.; Tiebout, H.M. III

1994-12-31

Wildlife toxicologists pioneered methodologies for assessing ecological risk to nontarget species. Historically, ecological risk assessments (ERAS) focused on a limited array of species and were based on a relatively few population-level endpoints (mortality, reproduction). Currently, risk assessment models are becoming increasingly complex that factor in multi-species interactions (across trophic levels) and utilize an increasingly diverse number of ecologically significant endpoints. This trend suggests the increasing importance of safeguarding not only populations of individual species, but also the overall integrity of the larger biotic systems that support them. In this sense, ERAs are in alignment with Conservation Biology, an applied sciencemore » of ecological knowledge used to conserve biodiversity. A theoretical conservation biology model could be incorporated in ERAs to quantify impacts to biodiversity (structure, function or composition across levels of biological organization). The authors suggest that the Franklin-Noss model for evaluating biodiversity, with its nested, hierarchical approach, may provide a suitable paradigm for assessing and integrating the ecological risk that chemical contaminants pose to biological systems from the simplest levels (genotypes, individual organisms) to the most complex levels of organization (communities and ecosystems). The Franklin-Noss model can accommodate the existing ecotoxicological database and, perhaps more importantly, indicate new areas in which critical endpoints should be identified and investigated.« less

Restoration for the future: endpoints, targets, and indicators of progress and success

Treesearch

Daniel C. Dey; Callie Jo. Schweitzer

2014-01-01

Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly described and quantitative endpoints and intermediary targets are needed to...

'Systems toxicology' approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus.

PubMed

Bundy, Jacob G; Sidhu, Jasmin K; Rana, Faisal; Spurgeon, David J; Svendsen, Claus; Wren, Jodie F; Stürzenbaum, Stephen R; Morgan, A John; Kille, Peter

2008-06-03

New methods are needed for research into non-model organisms, to monitor the effects of toxic disruption at both the molecular and functional organism level. We exposed earthworms (Lumbricus rubellus Hoffmeister) to sub-lethal levels of copper (10-480 mg/kg soil) for 70 days as a real-world situation, and monitored both molecular (cDNA transcript microarrays and nuclear magnetic resonance-based metabolic profiling: metabolomics) and ecological/functional endpoints (reproduction rate and weight change, which have direct relevance to population-level impacts). Both of the molecular endpoints, metabolomics and transcriptomics, were highly sensitive, with clear copper-induced differences even at levels below those that caused a reduction in reproductive parameters. The microarray and metabolomic data provided evidence that the copper exposure led to a disruption of energy metabolism: transcripts of enzymes from oxidative phosphorylation were significantly over-represented, and increases in transcripts of carbohydrate metabolising enzymes (maltase-glucoamylase, mannosidase) had corresponding decreases in small-molecule metabolites (glucose, mannose). Treating both enzymes and metabolites as functional cohorts led to clear inferences about changes in energetic metabolism (carbohydrate use and oxidative phosphorylation), which would not have been possible by taking a 'biomarker' approach to data analysis. Multiple post-genomic techniques can be combined to provide mechanistic information about the toxic effects of chemical contaminants, even for non-model organisms with few additional mechanistic toxicological data. With 70-day no-observed-effect and lowest-observed-effect concentrations (NOEC and LOEC) of 10 and 40 mg kg-1 for metabolomic and microarray profiles, copper is shown to interfere with energy metabolism in an important soil organism at an ecologically and functionally relevant level.

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma

PubMed Central

Medeiros, Felipe A.

2017-01-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials. PMID:28475699

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma.

PubMed

Medeiros, Felipe A

2017-05-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials.

Biomarkers and surrogate endpoints in glaucoma clinical trials.

PubMed

Medeiros, Felipe A

2015-05-01

Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Determining significant endpoints for ecological risk analyses. 1998 annual progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinton, T.G.; Congdon, J.; Scott, D.

1998-06-01

'The goal of this report is to establish a protocol for assessing risks to non-human populations exposed to environmental stresses typically found on many DOE sites. The authors think that they can achieve this by using novel biological dosimeters in controlled, manipulative dose/effects experiments, and by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables (such as age-specific survivorship, reproductive output, age at maturity and longevity). This research is needed to determine the relevancy of sublethal cellular damage to the performance of individuals and populations exposed to chronic, low-level radiation, and radiation with concomitant exposuremore » to chemicals. They believe that a scientifically defensible endpoint for measuring ecological risks can only be determined once its understood the extent to which molecular damage from contaminant exposure is detrimental at the individual and population levels of biological organization. The experimental facility will allow them to develop a credible assessment tool for appraising ecological risks, and to evaluate the effects of radionuclide/chemical synergisms on non-human species. This report summarizes work completed midway of a 3-year project that began in November 1996. Emphasis to date has centered on three areas: (1) developing a molecular probe to measure stable chromosomal aberrations known as reciprocal translocations, (2) constructing an irradiation facility where the statistical power inherent in replicated mesocosms can be used to address the response of non-human organisms to exposures from low levels of radiation and metal contaminants, and (3) quantifying responses of organisms living in contaminated mesocosms and field sites.'« less

Approach and strategy for performing ecological risk assessments for the US Department of Energy`s Oak Ridge Reservation: 1995 revision

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suter, G.W. II; Sample, B.E.; Jones, D.S.

1995-09-01

The purpose of this document is to provide guidance for planning and performing ecological risk assessments (ERAs) on the Oak Ridge Reservation (ORR). It is the third such document prepared for this purpose. The first ecorisk strategy document described the ERA process and presented a tiered approach to ERAs appropriate to complex sites. The first revision was necessitated by the considerable progress that has been made by the parties to the Federal Facilities Agreement (FFA) for the ORR in resolving specific issues relating to ERA as a result of a series of data quality objectives (DQOs) meetings. The tiered approachmore » to ERAs as recommended in the first document was implemented, generic conceptual models were developed, and a general approach for developing ecological assessment endpoints and measurement endpoints was agreed upon. This revision is necessitated by comments from the US Environmental Protection Agency`s Region IV and the Tennessee Department of Environment and Conservation (TDEC) which clarified and modified the positions taken during the DQO process. In particular, support for the collection of data that would support ERAs for all OUs on the ORR have been withdrawn. Therefore, the work plan developed to fill the reservation-wide data needs identified in the DQO process has also been withdrawn, and portions that are still relevant have been incorporated into this document. The reader should be aware that this guidance is complex and lengthy because it attempts to cover all the reasonable contingencies that were considered to be potentially important to the FFA parties.« less

Comparing the acute sensitivity of growth and photosynthetic endpoints in three Lemna species exposed to four herbicides.

PubMed

Park, Jihae; Brown, Murray T; Depuydt, Stephen; Kim, Jang K; Won, Dam-Soo; Han, Taejun

2017-01-01

An ecological impact assessment of four herbicides (atrazine, diuron, paraquat and simazine) was assessed using the aquatic floating vascular plants, Lemna gibba, Lemna minor and Lemna paucicostata as test organisms. The sensitivity of several ecologically relevant parameters (increase in frond area, root length after regrowth, maximum and effective quantum yield of PSII and maximum electron transport rate (ETR max ), were compared after a 72 h exposure to herbicides. The present test methods require relatively small sample volume (3 mL), shorter exposure times (72 h), simple and quick analytical procedures as compared with standard Lemna assays. Sensitivity ranking of endpoints, based on EC 50 values, differed depending on the herbicide. The most toxic herbicides were diuron and paraquat and the most sensitive endpoints were root length (6.0-12.3 μg L -1 ) and ETR max (4.7-10.3 μg L -1 ) for paraquat and effective quantum yield (6.8-10.4 μg L -1 ) for diuron. Growth and chlorophyll a fluorescence parameters in all three Lemna species were sensitive enough to detect toxic levels of diuron and paraquat in water samples in excess of allowable concentrations set by international standards. CV values of all EC 50 s obtained from the Lemna tests were in the range of 2.8-24.33%, indicating a high level of repeatability comparable to the desirable level of <30% for adoption of toxicity test methods as international standards. Our new Lemna methods may provide useful information for the assessment of toxicity risk of residual herbicides in aquatic ecosystems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Restoration for the future: Setting endpoints and targets and selecting indicators of progress and success

Treesearch

Daniel C. Dey; Callie Jo Schweitzer; John M. Kabrick

2014-01-01

Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly written and quantitative endpoints and intermediary targets need to be...

Growth Recovery of Lemna gibba and Lemna minor Following a 7-Day Exposure to the Herbicide Diuron.

PubMed

Burns, Mitchell; Hanson, Mark L; Prosser, Ryan S; Crossan, Angus N; Kennedy, Ivan R

2015-08-01

In agricultural catchments, aquatic ecosystems can experience a pulse exposure to pesticides. Following such exposure, non-target organisms that are not extirpated may recover. This paper investigates the potential of two duckweed species (Lemna minor and Lemna gibba) to recover from a 7-day exposure to different concentrations (0.4-208 µg L(-1)) of the herbicide diuron. There was significant inhibition in the growth and biomass after the initial 7-day exposure (e.g. frond number EC50=59.2 and 52.2 µg L(-1) for L. minor and L. gibba, respectively). Following transfer to clean media, recovery (the highest concentration yielding no significant difference in the effect endpoint from the control) was observed for all effects endpoints at concentrations ranging 60-111 µg L(-1) for L. minor and 60-208 µg L(-1) for L. gibba. These results suggest that recovery is possible for primary producers at environmentally relevant concentrations considered significant in ecological risk assessment.

Guidance for Using Non-Definitive Endpoints in Evaluating Risks to Listed and Non-listed Animal Species

EPA Pesticide Factsheets

Ensure consistency among OPP scientists in the use of non-definitive toxicity endpoints for terrestrial and aquatic animals when conducting ecological risk assessments for pesticides and federally listed and non-listed species.

Estrogenic chemical effects are independent from the degree of sex role reversal in pipefish.

PubMed

Sárria, Marisa P; Santos, Miguel M; Castro, L Filipe C; Vieira, Natividade M; Monteiro, Nuno M

2013-12-15

Endocrine disrupting chemicals (EDCs) have been reported to disturb several ecological relevant endpoints. Surprisingly, EDC-induced effects on fish sexual behaviour have been poorly studied despite the fact that even subtle alterations might contribute to a disruption of sexual interactions, thus negatively impacting reproduction. As the few assessments on sexual behaviour have been conducted in species with orthodox sex roles, it might be argued that sex-role reversed species might provide a potentially complementary system to further explore the effects of EDCs on reproduction. In the present study, two pipefish species with distinct degrees of sex-role reversal were selected to further elucidate the impact of chronic EE2 exposure on sexual behaviour and reproduction-related endpoints. The obtained results indicate that, independently of the degree of sex role reversal, courtship behaviour seems to resist oestrogenic chemical exposure. However, exposure to environmentally relevant EE2 levels did induce a complete absence of pregnancies at 18 ng/L. Even though pregnancies were observed at intermediate concentrations, the percentage of non-transferred or misplaced oocytes increased and a dose-dependent decrease of oocyte volume was observed. Imbalances in the oogenesis process, induction of vitellogenin in males and the absence of pregnancies highlight that environmental relevant concentrations of EE2 have the potential to negatively affect pipefish populations, most of them inhabiting coastal areas where oestrogenic contamination is more prevalent. Copyright © 2013 Elsevier B.V. All rights reserved.

Summary Report: Risk Assessment Forum Technical Workshop on Population-level Ecological Risk Assessment

EPA Pesticide Factsheets

2008 technical workshop regarding development of additional guidelines or best practices for planning, implementing and interpreting ecological risk assessments that involve population-level assessment endpoints.

Should I use that model? Assessing the transferability of ecological models to new settings

EPA Science Inventory

Analysts and scientists frequently apply existing models that estimate ecological endpoints or simulate ecological processes to settings where the models have not been used previously, and where data to parameterize and validate the model may be sparse. Prior to transferring an ...

Progression-free survival in advanced ovarian cancer: a Canadian review and expert panel perspective

PubMed Central

Oza, A.M.; Castonguay, V.; Tsoref, D.; Diaz–Padilla, I.; Karakasis, K.; Mackay, H.; Welch, S.; Weberpals, J.; Hoskins, P.; Plante, M.; Provencher, D.; Tonkin, K.; Covens, A.; Ghatage, P.; Gregoire, J.; Hirte, H.; Miller, D.; Rosen, B.; Maroun, J.; Buyse, M.; Coens, C.; Brady, M.F.; Stuart, G.C.E.

2011-01-01

Ovarian cancer is leading cause of gynecologic cancer mortality in Canada. To date, overall survival (os) has been the most-used endpoint in oncology trials because of its relevance and objectivity. However, as a result of various factors, including the pattern of sequential salvage therapies, measurement of os and collection of os data are becoming particularly challenging. Phase ii and iii trials have therefore adopted progression-free survival (pfs) as a more convenient surrogate endpoint; however, the clinical significance of pfs remains unclear. This position paper presents discussion topics and findings from a pan-Canadian meeting of experts that set out to evaluate the relevance of pfs as a valid endpoint in ovarian cancer;reach a Canadian consensus on the relevance of pfs in ovarian cancer; andtry to address how pfs translates into clinical benefit in ovarian cancer. Overall, the findings and the group consensus posit that future studies should ensure that trials are designed to evaluate pfs, os, and other clinically relevant endpoints such as disease-related symptoms or quality of life;incorporate interim futility analyses intended to stop accrual early when the experimental regimen is not active;stop trials early to declare superiority only when compelling evidence suggests that a new treatment provides benefit for a pre-specified, clinically relevant endpoint such as os or symptom relief; anddiscourage early release of secondary endpoint results when such a release might increase the frequency of crossover to the experimental intervention. PMID:21969808

Derivation of aquatic predicted no-effect concentration (PNEC) for ibuprofen and sulfamethoxazole based on various toxicity endpoints and the associated risks.

PubMed

Huang, Qiusen; Bu, Qingwei; Zhong, Wenjue; Shi, Kaichong; Cao, Zhiguo; Yu, Gang

2018-02-01

For pharmaceuticals, the ecological risk assessment based on traditional endpoints of toxicity could not be properly protective in the long run since the mode of action could vary because they are intended for different therapeutic uses. In this study, the predicted no-effect concentrations (PNECs) of two selected pharmaceuticals, ibuprofen (IBU) and sulfamethoxazole (SMX), were derived based on either traditional endpoints of survival and growth data or some nonlethal endpoints such as reproduction, biochemical and molecular data. The PNECs of IBU based on biochemical-cellular and reproduction data were 0.018 and 0.026 μg L -1 that were significantly lower than those derived from other endpoints, while the lowest PNEC for SMX derived from growth data with the concentration of 0.89 μg L -1 . Ecological risk assessment was performed for IBU and SMX to the aquatic environment by applying hazard quotient and probabilistic distribution based quotient (DBQs) methods. The results showed that the probability of DBQs of IBU exceeding 0.1 was 11.2%, while for SMX the probability was 0.9% that could be neglected. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phytotoxicity of atrazine, isoproturon, and diuron to submersed macrophytes in outdoor mesocosms.

PubMed

Knauert, Stefanie; Singer, Heinz; Hollender, Juliane; Knauer, Katja

2010-01-01

The submersed macrophytes Elodea canadensis, Myriophyllum spicatum and Potamogeton lucens were constantly exposed over a five-week period to environmentally relevant concentrations of atrazine, isoproturon, diuron, and their mixture in outdoor mesocosms. Effects were evaluated investigating photosynthetic efficiency (PE) of the three macrophytes and growth of M. spicatum and E. canadensis. Adverse effects on PE were observed on days 2 and 5 after application. M. spicatum was found to be the more sensitive macrophyte. E. canadensis and P. lucens were less sensitive to atrazine, diuron and the mixture and insensitive to isoproturon. PE of M. spicatum was similarly affected by the single herbicides and the mixture demonstrating concentration addition. Growth of E. canadensis and M. spicatum was not reduced indicating that herbicide exposure did not impair plant development. Although PE measurements turned out to be a sensitive method to monitor PSII herbicides, plant growth remains the more relevant ecological endpoint in risk assessment.

Communicating ecological importance in a risk-based world: linking numeric nutrient criteria to waterbody expectations

NASA Astrophysics Data System (ADS)

Kaufman, G.; Crawford, T. N.

2016-12-01

To protect the integrity of US waters, the Clean Water Act calls for the development of water quality standards. One key component of standards is limits for pollutants, known as water quality criteria. A cornerstone of deriving water quality criteria is determining how nutrients and other chemicals affect the goals for a waterbody set by a state or tribe, known as designated uses. By establishing a quantifiable and predictable relationship between nutrients and nutrient sensitive organisms and processes, known as assessment endpoints, researchers can help policy makers to address the consequences of pollution in a risk-based, understandable way tied to the goals for a waterbody. Furthermore, public buy-in and effectiveness of criteria can be enhanced by using endpoints to show the connection between nutrient pollution and the uses of waters that are important to the public. This talk will communicate the work done by the US Environmental Protection Agency in cooperation with state, federal, and academic partners to explore the connections between biological and ecological responses and nutrient pollution to derive numeric nutrient criteria in estuarine and coastal waters. The presentation will examine the variety of endpoints that have been used in the work of various research efforts and assessment frameworks. Examples will also be given of numeric nutrient criteria development using assessment endpoints and some of the key decisions that were made during endpoint selection and criteria development will be discussed. Aspects of those decisions that will be presented include development of selection factors for endpoints, data considerations when selecting endpoints, and spatial and temporal representation of endpoints for criteria development. Promising endpoints and future research needs will also be highlighted.

Communicating ecological importance in a risk-based world: linking numeric nutrient criteria to waterbody expectations

NASA Astrophysics Data System (ADS)

Kaufman, G.; Crawford, T. N.

2016-02-01

To protect the integrity of US waters, the Clean Water Act calls for the development of water quality standards. One key component of standards is limits for pollutants, known as water quality criteria. A cornerstone of deriving water quality criteria is determining how nutrients and other chemicals affect the goals for a waterbody set by a state or tribe, known as designated uses. By establishing a quantifiable and predictable relationship between nutrients and nutrient sensitive organisms and processes, known as assessment endpoints, researchers can help policy makers to address the consequences of pollution in a risk-based, understandable way tied to the goals for a waterbody. Furthermore, public buy-in and effectiveness of criteria can be enhanced by using endpoints to show the connection between nutrient pollution and the uses of waters that are important to the public. This talk will communicate the work done by the US Environmental Protection Agency in cooperation with state, federal, and academic partners to explore the connections between biological and ecological responses and nutrient pollution to derive numeric nutrient criteria in estuarine and coastal waters. The presentation will examine the variety of endpoints that have been used in the work of various research efforts and assessment frameworks. Examples will also be given of numeric nutrient criteria development using assessment endpoints and some of the key decisions that were made during endpoint selection and criteria development will be discussed. Aspects of those decisions that will be presented include development of selection factors for endpoints, data considerations when selecting endpoints, and spatial and temporal representation of endpoints for criteria development. Promising endpoints and future research needs will also be highlighted.

ECOLOGICAL ENDPOINT MODELING: EFFECTS OF SEDIMENT ON FISH POPULATIONS

EPA Science Inventory

Sediment is one of the main stressors of concern for TMDLs (Total Maximum Daily Loads) for streams, and often it is a concern because of its impact on biological endpoints. The National Research Council (NRC) has recommended that the EPA promote the development of models that ca...

The South Florida Ecosystem Portfolio Model - A Map-Based Multicriteria Ecological, Economic, and Community Land-Use Planning Tool

USGS Publications Warehouse

Labiosa, William B.; Bernknopf, Richard; Hearn, Paul; Hogan, Dianna; Strong, David; Pearlstine, Leonard; Mathie, Amy M.; Wein, Anne M.; Gillen, Kevin; Wachter, Susan

2009-01-01

The South Florida Ecosystem Portfolio Model (EPM) prototype is a regional land-use planning Web tool that integrates ecological, economic, and social information and values of relevance to decision-makers and stakeholders. The EPM uses a multicriteria evaluation framework that builds on geographic information system-based (GIS) analysis and spatially-explicit models that characterize important ecological, economic, and societal endpoints and consequences that are sensitive to regional land-use/land-cover (LULC) change. The EPM uses both economics (monetized) and multiattribute utility (nonmonetized) approaches to valuing these endpoints and consequences. This hybrid approach represents a methodological middle ground between rigorous economic and ecological/ environmental scientific approaches. The EPM sacrifices some degree of economic- and ecological-forecasting precision to gain methodological transparency, spatial explicitness, and transferability, while maintaining credibility. After all, even small steps in the direction of including ecosystem services evaluation are an improvement over current land-use planning practice (Boyd and Wainger, 2003). There are many participants involved in land-use decision-making in South Florida, including local, regional, State, and Federal agencies, developers, environmental groups, agricultural groups, and other stakeholders (South Florida Regional Planning Council, 2003, 2004). The EPM's multicriteria evaluation framework is designed to cut across the objectives and knowledge bases of all of these participants. This approach places fundamental importance on social equity and stakeholder participation in land-use decision-making, but makes no attempt to determine normative socially 'optimal' land-use plans. The EPM is thus a map-based set of evaluation tools for planners and stakeholders to use in their deliberations of what is 'best', considering a balancing of disparate interests within a regional perspective. Although issues of regional ecological sustainability can be explored with the EPM (for example, changes in biodiversity potential and regional habitat fragmentation), it does not attempt to define or evaluate long-term ecological sustainability as such. Instead, the EPM is intended to provide transparent first-order indications of the direction of ecological, economic, and community change, not to make detailed predictions of ecological, economic, and social outcomes. In short, the EPM is an attempt to widen the perspectives of its users by integrating natural and social scientific information in a framework that recognizes the diversity of values at stake in South Florida land-use planning. For terrestrial ecosystems, land-cover change is one of the most important direct drivers of changes in ecosystem services (Hassan and others, 2005). More specifically, the fragmentation of habitat from expanding low-density development across landscapes appears to be a major driver of terrestrial species decline and the impairment of terrestrial ecosystem integrity, in some cases causing irreversible impairment from a land-use planning perspective (Brody, 2008; Peck, 1998). Many resource managers and land-use planners have come to realize that evaluating land-use conversions on a parcel-by-parcel basis leads to a fragmented and narrow view of the regional effects of natural land-cover loss to development (Marsh and Lallas, 1995). The EPM is an attempt to integrate important aspects of the coupled natural-system/human-system view from a regional planning perspective. The EPM evaluates proposed land-use changes, both conversion and intensification, in terms of relevant ecological, economic, and social criteria that combine information about probable land-use outcomes, based on ecological and environmental models, as well as value judgments, as expressed in user-modifiable preference models. Based on on-going meetings and interviews with stakeholders and potential tool users we foc

Ecologically-focused Calibration of Hydrological Models for Environmental Flow Applications

NASA Astrophysics Data System (ADS)

Adams, S. K.; Bledsoe, B. P.

2015-12-01

Hydrologic alteration resulting from watershed urbanization is a common cause of aquatic ecosystem degradation. Developing environmental flow criteria for urbanizing watersheds requires quantitative flow-ecology relationships that describe biological responses to streamflow alteration. Ideally, gaged flow data are used to develop flow-ecology relationships; however, biological monitoring sites are frequently ungaged. For these ungaged locations, hydrologic models must be used to predict streamflow characteristics through calibration and testing at gaged sites, followed by extrapolation to ungaged sites. Physically-based modeling of rainfall-runoff response has frequently utilized "best overall fit" calibration criteria, such as the Nash-Sutcliffe Efficiency (NSE), that do not necessarily focus on specific aspects of the flow regime relevant to biota of interest. This study investigates the utility of employing flow characteristics known a priori to influence regional biological endpoints as "ecologically-focused" calibration criteria compared to traditional, "best overall fit" criteria. For this study, 19 continuous HEC-HMS 4.0 models were created in coastal southern California and calibrated to hourly USGS streamflow gages with nearby biological monitoring sites using one "best overall fit" and three "ecologically-focused" criteria: NSE, Richards-Baker Flashiness Index (RBI), percent of time when the flow is < 1 cfs (%<1), and a Combined Calibration (RBI and %<1). Calibrated models were compared using calibration accuracy, environmental flow metric reproducibility, and the strength of flow-ecology relationships. Results indicate that "ecologically-focused" criteria can be calibrated with high accuracy and may provide stronger flow-ecology relationships than "best overall fit" criteria, especially when multiple "ecologically-focused" criteria are used in concert, despite inabilities to accurately reproduce additional types of ecological flow metrics to which the models are not explicitly calibrated.

Effects of atrazine in fish, amphibians, and reptiles: an analysis based on quantitative weight of evidence.

PubMed

Van Der Kraak, Glen J; Hosmer, Alan J; Hanson, Mark L; Kloas, Werner; Solomon, Keith R

2014-12-01

A quantitative weight of evidence (WoE) approach was developed to evaluate studies used for regulatory purposes, as well as those in the open literature, that report the effects of the herbicide atrazine on fish, amphibians, and reptiles. The methodology for WoE analysis incorporated a detailed assessment of the relevance of the responses observed to apical endpoints directly related to survival, growth, development, and reproduction, as well as the strength and appropriateness of the experimental methods employed. Numerical scores were assigned for strength and relevance. The means of the scores for relevance and strength were then used to summarize and weigh the evidence for atrazine contributing to ecologically significant responses in the organisms of interest. The summary was presented graphically in a two-dimensional graph which showed the distributions of all the reports for a response. Over 1290 individual responses from studies in 31 species of fish, 32 amphibians, and 8 reptiles were evaluated. Overall, the WoE showed that atrazine might affect biomarker-type responses, such as expression of genes and/or associated proteins, concentrations of hormones, and biochemical processes (e.g. induction of detoxification responses), at concentrations sometimes found in the environment. However, these effects were not translated to adverse outcomes in terms of apical endpoints. The WoE approach provided a quantitative, transparent, reproducible, and robust framework that can be used to assist the decision-making process when assessing environmental chemicals. In addition, the process allowed easy identification of uncertainty and inconsistency in observations, and thus clearly identified areas where future investigations can be best directed.

Linking ecosystem characteristics to final ecosystem services for public policy.

PubMed

Wong, Christina P; Jiang, Bo; Kinzig, Ann P; Lee, Kai N; Ouyang, Zhiyun

2015-01-01

Governments worldwide are recognising ecosystem services as an approach to address sustainability challenges. Decision-makers need credible and legitimate measurements of ecosystem services to evaluate decisions for trade-offs to make wise choices. Managers lack these measurements because of a data gap linking ecosystem characteristics to final ecosystem services. The dominant method to address the data gap is benefit transfer using ecological data from one location to estimate ecosystem services at other locations with similar land cover. However, benefit transfer is only valid once the data gap is adequately resolved. Disciplinary frames separating ecology from economics and policy have resulted in confusion on concepts and methods preventing progress on the data gap. In this study, we present a 10-step approach to unify concepts, methods and data from the disparate disciplines to offer guidance on overcoming the data gap. We suggest: (1) estimate ecosystem characteristics using biophysical models, (2) identify final ecosystem services using endpoints and (3) connect them using ecological production functions to quantify biophysical trade-offs. The guidance is strategic for public policy because analysts need to be: (1) realistic when setting priorities, (2) attentive to timelines to acquire relevant data, given resources and (3) responsive to the needs of decision-makers. © 2014 The Authors. Ecology Letters published by John Wiley & Sons Ltd and CNRS.

Birds and flame retardants: A review of the toxic effects on birds of historical and novel flame retardants.

PubMed

Guigueno, Mélanie F; Fernie, Kim J

2017-04-01

Flame retardants (FRs) are a diverse group of chemicals, many of which persist in the environment and bioaccumulate in biota. Although some FRs have been withdrawn from manufacturing and commerce (e.g., legacy FRs), many continue to be detected in the environment; moreover, their replacements and/or other novel FRs are also detected in biota. Here, we review and summarize the literature on the toxic effects of various FRs on birds. Birds integrate chemical information (exposure, effects) across space and time, making them ideal sentinels of environmental contamination. Following an adverse outcome pathway (AOP) approach, we synthesized information on 8 of the most commonly reported endpoints in avian FR toxicity research: molecular measures, thyroid-related measures, steroids, retinol, brain anatomy, behaviour, growth and development, and reproduction. We then identified which of these endpoints appear more/most sensitive to FR exposure, as determined by the frequency of significant effects across avian studies. The avian thyroid system, largely characterized by inconsistent changes in circulating thyroid hormones that were the only measure in many such studies, appears to be moderately sensitive to FR exposure relative to the other endpoints; circulating thyroid hormones, after reproductive measures, being the most frequently examined endpoint. A more comprehensive examination with concurrent measurements of multiple thyroid endpoints (e.g., thyroid gland, deiodinase enzymes) is recommended for future studies to more fully understand potential avian thyroid toxicity of FRs. More research is required to determine the effects of various FRs on avian retinol concentrations, inconsistently sensitive across species, and to concurrently assess multiple steroid hormones. Behaviour related to courtship and reproduction was the most sensitive of all selected endpoints, with significant effects recorded in every study. Among domesticated species (Galliformes), raptors (Accipitriformes and Falconiformes), songbirds (Passeriformes), and other species of birds (e.g. gulls), raptors seem to be the most sensitive to FR exposure across these measurements. We recommend that future avian research connect biochemical disruptions and changes in the brain to ecologically relevant endpoints, such as behaviour and reproduction. Moreover, connecting in vivo endpoints with molecular endpoints for non-domesticated avian species is also highly important, and essential to linking FR exposure with reduced fitness and population-level effects. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Using a multibiomarker approach and behavioural responses to assess the effects of anthracene in Palaemon serratus.

PubMed

Gravato, Carlos; Almeida, Joana R; Silva, Carlos; Oliveira, Cristiana; Soares, Amadeu M V M

2014-04-01

Polycyclic aromatic hydrocarbons (PAHs) are recognised as one of the main groups of contaminants that assume more importance in the marine environment, enhancing the need of studies concerning their adverse effects and more efficient and ecologically relevant tools for environmental monitoring purposes. This study aims to apply an integrated approach including several multi-level biological responses (accumulation levels, biochemical responses important for different physiological functions and behavioural alterations) to assess the ecological relevance of the effects induced by sub-lethal concentrations of anthracene (ANT) in Palaemon serratus (common prawn). ANT accumulation was assessed by measuring the levels of ANT-type compounds in prawn digestive gland, muscle and eye; biochemical responses were determined using biomarkers involved in biotransformation, oxidative damage, energy production and neurotransmission processes; and behavioural alterations through swimming performance after 96 h exposure bioassay (ANT:16-1,024 μg/L). The rationale behind this approach is to assess the ecologically relevant effects induced by ANT in prawn, given by the association between behavioural alterations with biochemical responses, in search for more efficient tools for environmental risk assessment. Results show a significant decrease of swimming velocity (LOEC=128 μg/L) along with increased levels of ANT-type compounds in digestive gland (LOEC=128 μg/L), muscle (LOEC=256 μg/L) and eye (LOEC=32 μg/L) in prawn exposed to ANT. Increased activities of glutathione peroxidase (GPx) and catalase (CAT), involved in anti-oxidant defence system, were also observed (LOEC=256 μg/L; 1024μg/L, respectively) in the digestive gland of prawn, induction of oxidative damage in lipids (LPO) also occurred (LOEC=32 μg/L). The inhibition of swimming velocity showed a correlation with some biochemical parameters measured, including the levels of ANT-type compounds in tissues and LPO, and thus these may be considered sensitive and ecologically relevant criteria as well as early warning endpoints for assessing polycyclic aromatic compounds exposure effects on marine organisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Organism and population-level ecological models for chemical risk assessment

EPA Science Inventory

Ecological risk assessment typically focuses on animal populations as endpoints for regulatory ecotoxicology. Scientists at USEPA are developing models for animal populations exposed to a wide range of chemicals from pesticides to emerging contaminants. Modeled taxa include aquat...

FROM MOLECULES TO POPULATIONS: USING POPULATION GENETICS TO ANSWER THE SO WHAT QUESTION

EPA Science Inventory

Important endpoints for ecological risk assessments are usually those that affect population or species persistence rather than individual-level responses. Nonetheless, ecological risk assessments are generally based on measures of individual-level responses. Extrapolation of i...

Development of DNA-Free Sediment for Ecological Assays with Genomic Endpoints

EPA Science Inventory

Recent advances in genomics are currently being exploited to discern ecological changes that have conventionally been measured using laborious counting techniques. For example, next generation sequencing technologies can be used to create DNA libraries from benthic community ass...

Development of a relative risk model for evaluating ecological risk of water environment in the Haihe River Basin estuary area.

PubMed

Chen, Qiuying; Liu, Jingling; Ho, Kin Chung; Yang, Zhifeng

2012-03-15

Ecological risk assessment for water environment is significant to water resource management of basin. Effective environmental management and systems restoration such as the Haihe River Basin require holistic understanding of the relative importance of various stressor-related impacts throughout the basin. As an effective technical tool for evaluating the ecological risk, relative risk model (RRM) was applied in regional scale successfully. In this study, the risk transfer from upstream of basin was considered and the RRM was developed through introducing the source-stressor-habitat exposure filter (SSH), the endpoint-habitat exposure filter (EH) and the stressor-endpoint effect filter (SE) to reflect the meaning of exposure and effect more explicit. Water environment which includes water quality, water quantity and aquatic ecosystems was selected as the assessment endpoints. We created a conceptual model which depicting potential and effect pathways from source to stressor to habitat to endpoint. The Haihe River Basin estuary (HRBE) was selected as the model case. The results showed that there were two low risk regions, one medium risk region and two high risk regions in the HRBE. The results also indicated that urbanization was the biggest source, the second was shipping and the third was industry, their risk scores are 5.65, 4.71 and 3.68 respectively. Furthermore, habitat destruction was the largest stressor with the risk scores (2.66), the second was oxygen consuming organic pollutants (1.75) and the third was pathogens (1.75). So these three stressors were the main influencing factors of the ecological pressure in the study area. For habitats, open waters (9.59) and intertidal mudflat were enduring the bigger pressure and should be taken considerable attention. Ecological service values damaged (30.54) and biodiversity decreased were facing the biggest risk pressure. Copyright © 2011 Elsevier B.V. All rights reserved.

Useful pharmacodynamic endpoints in children: selection, measurement, and next steps

PubMed Central

Kelly, Lauren E; Sinha, Yashwant; Barker, Charlotte I S; Standing, Joseph F; Offringa, Martin

2018-01-01

Pharmacodynamic (PD) endpoints are essential for establishing the benefit-to-risk ratio for therapeutic interventions in children and neonates. This article discusses the selection of an appropriate measure of response, the PD endpoint, which is a critical methodological step in designing pediatric efficacy and safety studies. We provide an overview of existing guidance on the choice of PD endpoints in pediatric clinical research. We identified several considerations relevant to the selection and measurement of PD endpoints in pediatric clinical trials, including the use of biomarkers, modeling, compliance, scoring systems, and validated measurement tools. To be useful, PD endpoints in children need to be clinically relevant, responsive to both treatment and/or disease progression, reproducible, and reliable. In most pediatric disease areas, this requires significant validation efforts. We propose a minimal set of criteria for useful PD endpoint selection and measurement. We conclude that, given the current heterogeneity of pediatric PD endpoint definitions and measurements, both across and within defined disease areas, there is an acute need for internationally agreed, validated, and condition-specific pediatric PD endpoints that consider the needs of all stakeholders, including healthcare providers, policy makers, patients, and families. PMID:29667952

Capturing ecology in modeling approaches applied to environmental risk assessment of endocrine active chemicals in fish.

PubMed

Mintram, Kate S; Brown, A Ross; Maynard, Samuel K; Thorbek, Pernille; Tyler, Charles R

2018-02-01

Endocrine active chemicals (EACs) are widespread in freshwater environments and both laboratory and field based studies have shown reproductive effects in fish at environmentally relevant exposures. Environmental risk assessment (ERA) seeks to protect wildlife populations and prospective assessments rely on extrapolation from individual-level effects established for laboratory fish species to populations of wild fish using arbitrary safety factors. Population susceptibility to chemical effects, however, depends on exposure risk, physiological susceptibility, and population resilience, each of which can differ widely between fish species. Population models have significant potential to address these shortfalls and to include individual variability relating to life-history traits, demographic and density-dependent vital rates, and behaviors which arise from inter-organism and organism-environment interactions. Confidence in population models has recently resulted in the EU Commission stating that results derived from reliable models may be considered when assessing the relevance of adverse effects of EACs at the population level. This review critically assesses the potential risks posed by EACs for fish populations, considers the ecological factors influencing these risks and explores the benefits and challenges of applying population modeling (including individual-based modeling) in ERA for EACs in fish. We conclude that population modeling offers a way forward for incorporating greater environmental relevance in assessing the risks of EACs for fishes and for identifying key risk factors through sensitivity analysis. Individual-based models (IBMs) allow for the incorporation of physiological and behavioral endpoints relevant to EAC exposure effects, thus capturing both direct and indirect population-level effects.

Development of DNA-Free Sediment for Ecological Assays with Genomic Endpoints (NAC SETAC)

EPA Science Inventory

Recent advances in genomics are currently being exploited to discern ecological changes that have conventionally been measured using laborious counting techniques. For example, next generation sequencing technologies can be used to create DNA libraries from benthic community ass...

Direct soil contact values for ecological receptors exposed to weathered petroleum hydrocarbon (PHC) fraction 2.

PubMed

Angell, Robin A; Kullman, Steve; Shrive, Emma; Stephenson, Gladys L; Tindal, Miles

2012-11-01

Ecological tier 1 Canada-wide standards (CWS) for petroleum hydrocarbon (PHC) fraction 2 (F2; >nC10-C16) in soil were derived using ecotoxicological assessment endpoints (effective concentrations [ECs]/lethal concentrations [LCs]/inhibitory concentrations, 25% [IC25s]) with freshly spiked (fresh) fine- and coarse-grained soils. These soil standards might be needlessly conservative when applied to field samples with weathered hydrocarbons. The purpose of the present study was to assess the degradation and toxicity of weathered PHC F2 in a fine-grained soil and to derive direct soil contact values for ecological receptors. Fine-grained reference soils were spiked with distilled F2 and weathered for 183 d. Toxicity tests using plants and invertebrates were conducted with the weathered F2-spiked soils. Endpoint EC/IC25s were calculated and used to derive soil standards for weathered F2 in fine-grained soil protective of ecological receptors exposed via direct soil contact. The values derived for weathered F2 were less restrictive than current ecological tier 1 CWS for F2 in soil. Copyright © 2012 SETAC.

A framework for predicting impacts on ecosystem services from (sub)organismal responses to chemicals

Treesearch

Valery E. Forbes; Chris J. Salice; Bjorn Birnir; Randy J.F. Bruins; Peter Calow; Virginie Ducrot; Nika Galic; Kristina Garber; Bret C. Harvey; Henriette Jager; Andrew Kanarek; Robert Pastorok; Steve F. Railsback; Richard Rebarber; Pernille Thorbek

2017-01-01

Protection of ecosystem services is increasingly emphasized as a risk-assessment goal, but there are wide gaps between current ecological risk-assessment endpoints and potential effects on services provided by ecosystems. The authors present a framework that links common ecotoxicological endpoints to chemical impacts on populations and communities and the ecosystem...

DEVELOPMENT OF QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS (QSARS) TO PREDICT TOXICITY FOR A VARIETY OF HUMAN AND ECOLOGICAL ENDPOINTS

EPA Science Inventory

A web accessible software tool is being developed to predict the toxicity of unknown chemicals for a wide variety of endpoints. The tool will enable a user to easily predict the toxicity of a query compound by simply entering its structure in a 2-dimensional (2-D) chemical sketc...

Post hoc analyses: after the facts.

PubMed

Srinivas, Titte R; Ho, Bing; Kang, Joseph; Kaplan, Bruce

2015-01-01

Prospective clinical trials are constructed with high levels of internal validity. Sample size and power considerations usually address primary endpoints. Primary endpoints have traditionally included events that are becoming increasingly less common and thus have led to growing use of composite endpoints and noninferiority trial designs in transplantation. This approach may mask real clinical benefit in one or the other domain with regard to either clinically relevant secondary endpoints or other unexpected findings. In addition, endpoints solely chosen based on power considerations are prone to misjudgment of actual treatment effect size as well as consistency of that effect. In the instances where treatment effects may have been underestimated, valuable information may be lost if buried within a composite endpoint. In all these cases, analyses and post hoc analyses of data become relevant in informing practitioners about clinical benefits or safety signals that may not be captured by the primary endpoint. On the other hand, there are many pitfalls in using post hoc determined endpoints. This short review is meant to allow readers to appreciate post hoc analysis not as an entity with a single approach, but rather as an analysis with unique limitations and strengths that often raise new questions to be addressed in further inquiries.

Ecosystem services as assessment endpoints for ecological risk assessment

EPA Science Inventory

Ecosystem services (ES) are defined as the outputs of ecological processes that contribute to human welfare or have the potential to do so in the future, and include the production of food and drinking water, purification of air and water, pollination, and nutrient cycling. The n...

Use of behavioral endpoints to determine protective concentrations of the insecticide fonofos for bluegill (Lepomis macrochirus)

USGS Publications Warehouse

Fairchild, J.F.; Little, E.E.

1999-01-01

This research compared the results of laboratory and mesocosm studies to determine the effectiveness of using behavioral measures of sublethal exposure to define environmental concentration ranges that are protective of free-ranging populations of bluegill (Lepomis macrochirus) exposed to the organophophate insecticide fonofos. Thirty-day laboratory chronic studies were conducted to determine the relative sensitivity of standard (e.g. survival and growth) and non-standard behavioral (e.g. swimming capacity, feeding efficiency, and aggression) endpoints in predicting concentrations of fonofos protective of bluegill growth and survival. The lowest observable effect concentration (LOECs) for the standard measures of survival and growth was 5.6 ??g/L. Two behavioral endpoints were of similar sensitivity to the standard measures: swimming capacity, LOEC of 5.6 ??g/L; and prey strike frequency, LOEC of 5.6 ??g/L. However, aggressive interactions were ten-fold more sensitive than swimming or feeding behavior with a LOEC occurring at 0.6 ??g/L. Lab results were compared to an aquatic mesocosm study which exposed adult and juvenile bluegill to a 9.41 ??g/L concentration of fonofos. The dissipation half-life of fonofos was 5 days in 0.1 hectare aquatic mesocosms. Significant mortality among caged bluegill occurred within 4 days of exposure at 9.41 ??g/L. However, the 9.41 ??g/L concentration of fonofos had no statistically significant effects on survival, growth, reproduction, or total biomass of free-ranging populations of bluegill. We conclude from these studies that laboratory data can accurately estimate concentrations that are lethal in the field and that the use of behavioral endpoints can provide ecologically relevant, yet conservative estimates of concentrations that are protective of field populations.

Health effects of metoprolol in epibenthic and endobenthic invertebrates-A basis to validate future in vitro biotests for effect-based biomonitoring.

PubMed

Jungmann, Dirk; Berg, Kristin; Dieterich, Andreas; Frank, Martin; Gräf, Tonya; Scheurer, Marco; Schwarz, Simon; Siewert, Carmen; Oetken, Matthias

2017-02-23

The aim of this study was to determine the effect data for metoprolol as a model substance for beta-blockers in aquatic invertebrates. The results will be used as a basis for the validation of future mode of action-based in vitro test systems targeting this class of pharmaceuticals. Effects of metoprolol were investigated in two autochthonous species with high relevance in stream ecology: the amphipod Gammarus fossarum and the oligochaete Lumbriculus variegatus. Mortality in G. fossarum was not observed in acute toxicity testing (48 h), and a significant increase of mortality at 45 mg/L was found when amphipods were exposed chronically (40 days). The most sensitive population-relevant endpoints were the juvenile-adult ratio and number of egg-bearing females with NOEC/LOEC-values of 5/15 mg/L. No proteotoxic effects were identified in G. fossarum. The sediment toxicity test with L. variegatus according to the OECD Guideline 225 with an exposure time of 28 days resulted in EC 10 -values of 92.5 and 126.1 mg/kg dw for the endpoints reproduction and biomass, respectively. In L. variegatus the response kinetics of Hsp70 showed no significant difference between the treatments. A tendency for rising lipid peroxide concentrations was found between 0.03 and 10 mg/kg dw , which were significant between the treatments, but not to the control.

Endpoints and surrogate endpoints in colorectal cancer: a review of recent developments.

PubMed

Piedbois, Pascal; Buyse, Marc

2008-07-01

The purpose of this review is to discuss recently published work on endpoints for early and advanced colorectal cancer, as well as the statistical approaches used to validate surrogate endpoints. Most attempts to validate surrogate endpoints have estimated the correlation between the surrogate and the true endpoint, and between the treatment effects on these endpoints. The correlation approach has made it possible to validate disease-free survival and progression-free survival as acceptable surrogates for overall survival in early and advanced disease, respectively. The search for surrogate endpoints will intensify over the coming years. In parallel, efforts to either standardize or extend the endpoints or both will improve the reliability and relevance of clinical trial results.

Ecological risk assessment for DvSnf7 RNA: A plant-incorporated protectant with targeted activity against western corn rootworm.

PubMed

Bachman, Pamela M; Huizinga, Kristin M; Jensen, Peter D; Mueller, Geoffrey; Tan, Jianguo; Uffman, Joshua P; Levine, Steven L

2016-11-01

MON 87411 maize, which expresses DvSnf7 RNA, was developed to provide an additional mode of action to confer protection against corn rootworm (Diabrotica spp.). A critical step in the registration of a genetically engineered crop with an insecticidal trait is performing an ecological risk assessment to evaluate the potential for adverse ecological effects. For MON 87411, an assessment plan was developed that met specific protection goals by characterizing the routes and levels of exposure, and testing representative functional taxa that would be directly or indirectly exposed in the environment. The potential for toxicity of DvSnf7 RNA was evaluated with a harmonized battery of non-target organisms (NTOs) that included invertebrate predators, parasitoids, pollinators, soil biota as well as aquatic and terrestrial vertebrate species. Laboratory tests evaluated ecologically relevant endpoints such as survival, growth, development, and reproduction and were of sufficient duration to assess the potential for adverse effects. No adverse effects were observed with any species tested at, or above, the maximum expected environmental concentration (MEEC). All margins of exposure for NTOs were >10-fold the MEEC. Therefore, it is reasonable to conclude that exposure to DvSnf7 RNA, both directly and indirectly, is safe for NTOs at the expected field exposure levels. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Comparison of the behavioural effects of pharmaceuticals and pesticides on Diamesa zernyi larvae (Chironomidae).

PubMed

Villa, Sara; Di Nica, Valeria; Pescatore, Tanita; Bellamoli, Francesco; Miari, Francesco; Finizio, Antonio; Lencioni, Valeria

2018-07-01

Several studies have indicated the presence of contaminants in Alpine aquatic ecosystems. Even if measured concentrations are far below those that cause acute effects, continuous exposure to sub-lethal concentrations may have detrimental effects on the aquatic species present in these remote environments. This may lead to a cascade of indirect effects at higher levels of the ecological hierarchy (i.e., the community). To improve the determination of ecologically relevant risk endpoints, behavioural alterations in organisms due to pollutants are increasingly studied in ecotoxicology. In fact, behaviour links physiological function with ecological processes, and can be very sensitive to environmental stimuli and chemical exposure. This is the first study on behavioural alteration in a wild population of an Alpine species. In the present study, a video tracking system was standardized and subsequently used to identify contaminant-induced behavioural alterations in Diamesa zernyi larvae (Diptera, Chironomidae). Diamesa zernyi larvae, collected in an Italian Alpine stream (Rio Presena, Trentino Region), were acclimated for 24 h and successively exposed to several aquatic contaminants (pesticides: chlorpyrifos, metolachlor, boscalid, captan; pharmaceuticals: ibuprofen, furosemide, trimethoprim) at concentrations corresponding to their Lowest Observed Effect Concentration (LOEC). After 24, 48, 72, and 96 h of exposure, changes in the distance moved, the average speed, and the frequency of body bends were taken to reflect contaminant- and time-dependent effects on larval behaviour. In general, metolachlor, captan, and trimethoprim tended to reduce all the endpoints under consideration, whereas chlorpyrifos, boscalid, ibuprofen, and furosemide seemed to increase the distances moved by the larvae. This could be related to the different mechanisms of action of the investigated chemicals. Independently of the contaminant, after 72 h a general slowing down of all the behavioural activities occurred. Finally, we propose a behavioural stress indicator to compare the overall behavioural effects induced by the various contaminants. Copyright © 2018 Elsevier Ltd. All rights reserved.

The consequences of landscape change on ecological resources: An assessment of the United States mid-Atlantic region, 1973-1993

USGS Publications Warehouse

Jones, K.B.; Neale, A.C.; Wade, T.G.; Wickham, J.D.; Cross, C.L.; Edmonds, C.M.; Loveland, Thomas R.; Nash, M.S.; Riitters, K.H.; Smith, E.R.

2001-01-01

Spatially explicit identification of changes in ecological conditions over large areas is key to targeting and prioritizing areas for environmental protection and restoration by managers at watershed, basin, and regional scales. A critical limitation to this point has been the development of methods to conduct such broad-scale assessments. Field-based methods have proven to be too costly and too inconsistent in their application to make estimates of ecological conditions over large areas. New spatial data derived from satellite imagery and other sources, the development of statistical models relating landscape composition and pattern to ecological endpoints, and geographic information systems (GIS) make it possible to evaluate ecological conditions at multiple scales over broad geographic regions. In this study, we demonstrate the application of spatially distributed models for bird habitat quality and nitrogen yield to streams to assess the consequences of landcover change across the mid-Atlantic region between the 1970s and 1990s. Moreover, we present a way to evaluate spatial concordance between models related to different environmental endpoints. Results of this study should help environmental managers in the mid-Atlantic region target those areas in need of conservation and protection.

Ultrasound and radiology surrogate endpoints in pharmacological studies.

PubMed

Agewall, S; DeGroot, E; Marcos-Alberca, P; Zamorano, J L; Barrero, A A; Badano, L P; Perrone-Filardi, P

2012-09-01

Cardiovascular studies investigating therapeutic intervention with clinical endpoints are costly due to the need for considerable duration and large number of patients, or both. Therefore, for evaluation of novel cardiovascular drug efficacy, surrogate endpoints are used. Cardiovascular imaging endpoints have proven their worth. Sometimes the relevance of imaging is questioned and other methods are suggested instead. There is also some confusion about the strengths of imaging endpoints. The aim of the present paper is to review ultrasound and radiology imaging techniques as surrogate endpoints in pharmacological trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A Framework to Quantify the Strength of the Ecological Links ...

EPA Pesticide Factsheets

Anthropogenic stressors such as climate change, fire, and pollution are driving shifts in ecosystem function and resilience. Scientists generally rely on biological indicators of these stressors to signal that ecosystem conditions have been altered beyond an acceptable amount. However, these biological indicators are not always capable of being directly related to ecosystem services that allow scientists to communicate the importance of the change to land managers and policy makers. Therefore, we developed the STEPS (STressor – Ecological Production function – final ecosystem goods and Services) Framework to link changes in a biological indicator of a stressor to Final Ecosystem Goods and Services (FEGS). The STEPS framework produces “chains” of ecological components that connect the change in a biological indicator to the Final Ecosystem Goods and Services Classification System (FEGS-CS). The series of ecological components is an ecological production functions (EPF) which links a biological indicator of a stressor to an ecological endpoint (i.e., FEGS) that is directly used, appreciated, or valued by humans. The framework uses a qualitative score (High, Medium, Low) for the Strength of Science (SOS) for the relationship between each of the components in the EPF to identify research gaps and prioritize decision making based on what research has been completed. The ecological endpoint of the EPF is a FEGS to which discrete Beneficiaries, or direct users

A sediment ecotoxicity assessment platform for in situ measures of chemistry, bioaccumulation and toxicity. Part 1: System description and proof of concept.

PubMed

Burton, G Allen; Rosen, Gunther; Chadwick, D Bart; Greenberg, Marc S; Taulbee, W Keith; Lotufo, Guilherme R; Reible, Danny D

2012-03-01

In situ-based testing using aquatic organisms has been widely reported, but is often limited in scope and practical usefulness in making decisions on ecological risk and remediation. To provide this capability, an integrated deployment system, the Sediment Ecotoxicity Assessment (SEA) Ring was developed, which incorporates rapid in situ hydrological, chemical, bioaccumulation, and toxicological Lines-of-Evidence (LoE) for assessing sediment and overlying water contamination. The SEA Ring system allows for diver-assisted, or diverless, deployment of multiple species of ecologically relevant and indigenous organisms in three different exposures (overlying water, sediment-water interface, and bulk sediment) for periods ranging from two days to three weeks, in a range of water systems. Measured endpoints were both sublethal and lethal effects as well as bioaccumulation. In addition, integrated passive sampling devices for detecting nonpolar organics (solid phase micro-extraction fibers) and metals (diffusive gradients in thin films) provided gradient measures in overlying waters and surficial sediments. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evaluation of the ecological relevance of mysid toxicity tests using population modeling techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhn-Hines, A.; Munns, W.R. Jr.; Lussier, S.

1995-12-31

A number of acute and chronic bioassay statistics are used to evaluate the toxicity and risks of chemical stressors to the mysid shrimp, Mysidopsis bahia. These include LC{sub 50}S from acute tests, NOECs from 7-day and life-cycle tests, and the US EPA Water Quality Criteria Criterion Continuous Concentrations (CCC). Because these statistics are generated from endpoints which focus upon the responses of individual organisms, their relationships to significant effects at higher levels of ecological organization are unknown. This study was conducted to evaluate the quantitative relationships between toxicity test statistics and a concentration-based statistic derived from exposure-response models describing populationmore » growth rate ({lambda}) to stressor concentration. This statistic, C{sup {sm_bullet}} (concentration where {lambda} = I, zero population growth) describes the concentration above which mysid populations are projected to decline in abundance as determined using population modeling techniques. An analysis of M. bahia responses to 9 metals and 9 organic contaminants indicated the NOEC from life-cycle tests to be the best predictor of C{sup {sm_bullet}}, although the acute LC{sub 50} predicted population-level response surprisingly well. These analyses provide useful information regarding uncertainties of extrapolation among test statistics in assessments of ecological risk.« less

Linking ecosystem characteristics to final ecosystem services for public policy

PubMed Central

Wong, Christina P; Jiang, Bo; Kinzig, Ann P; Lee, Kai N; Ouyang, Zhiyun

2015-01-01

Governments worldwide are recognising ecosystem services as an approach to address sustainability challenges. Decision-makers need credible and legitimate measurements of ecosystem services to evaluate decisions for trade-offs to make wise choices. Managers lack these measurements because of a data gap linking ecosystem characteristics to final ecosystem services. The dominant method to address the data gap is benefit transfer using ecological data from one location to estimate ecosystem services at other locations with similar land cover. However, benefit transfer is only valid once the data gap is adequately resolved. Disciplinary frames separating ecology from economics and policy have resulted in confusion on concepts and methods preventing progress on the data gap. In this study, we present a 10-step approach to unify concepts, methods and data from the disparate disciplines to offer guidance on overcoming the data gap. We suggest: (1) estimate ecosystem characteristics using biophysical models, (2) identify final ecosystem services using endpoints and (3) connect them using ecological production functions to quantify biophysical trade-offs. The guidance is strategic for public policy because analysts need to be: (1) realistic when setting priorities, (2) attentive to timelines to acquire relevant data, given resources and (3) responsive to the needs of decision-makers. PMID:25394857

Developing an Ecosystem Services Online Decision Support Tool to Assess the Impacts of Climate Change and Urban Growth in the Santa Cruz Watershed: Where We Live, Work, and Play

USGS Publications Warehouse

Norman, Laura; Tallent-Halsell, Nita; Labiosa, William; Weber, Matt; McCoy, Amy; Hirschboeck, Katie; Callegary, James; van Riper, Charles; Gray, Floyd

2010-01-01

Using respective strengths of the biological, physical, and social sciences, we are developing an online decision support tool, the Santa Cruz Watershed Ecosystem Portfolio Model (SCWEPM), to help promote the use of information relevant to water allocation and land management in a binational watershed along the U.S.-Mexico border. The SCWEPM will include an ES valuation system within a suite of linked regional driver-response models and will use a multicriteria scenario-evaluation framework that builds on GIS analysis and spatially-explicit models that characterize important ecological, economic, and societal endpoints and consequences that are sensitive to climate patterns, regional water budgets, and regional LULC change in the SCW.

Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists.

PubMed

Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

2010-06-10

Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion.Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS.DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations.Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed. The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.

Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

PubMed Central

2010-01-01

Background Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). Methods In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion. Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Results Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS. DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations. Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed. Conclusion The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient. PMID:20537166

Individual and Composite Study Endpoints: Separating the Wheat from the Chaff

PubMed Central

Goldberg, Robert; Gore, Joel M.; Barton, Bruce; Gurwitz, Jerry

2014-01-01

We provide an overview of the individual and combined clinical endpoints and patient reported outcomes typically used in clinical trials and prospective epidemiological investigations. We discuss the strengths and limitations associated with the utilization of aggregated study endpoints and surrogate measures of important clinical endpoints and patient-centered outcomes. We hope that the points raised in this overview will lead to the collection of clinically rich, relevant, measurable, and cost-efficient study outcomes. PMID:24486289

Building spatially-explicit model predictions for ecological condition of streams in the Pacific Northwest: An assessment of landscape variables, models, endpoints and prediction scale

EPA Science Inventory

While large-scale, randomized surveys estimate the percentage of a region’s streams in poor ecological condition, identifying particular stream reaches or watersheds in poor condition is an equally important goal for monitoring and management. We built predictive models of strea...

SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

NASA Astrophysics Data System (ADS)

Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas; Vandenbussche, Pierre-Yves

In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this method, most of the currently listed SPARQL endpoints in existing endpoint repositories, as well as a significant number of new SPARQL endpoints, have been discovered. Finally, we have developed a new SPARQL endpoint crawler (SpEC) for crawling and link analysis.

Deriving site-specific soil clean-up values for metals and metalloids: Rationale for including protection of soil microbial processes

PubMed Central

Kuperman, Roman G; Siciliano, Steven D; Römbke, Jörg; Oorts, Koen

2014-01-01

Although it is widely recognized that microorganisms are essential for sustaining soil fertility, structure, nutrient cycling, groundwater purification, and other soil functions, soil microbial toxicity data were excluded from the derivation of Ecological Soil Screening Levels (Eco-SSL) in the United States. Among the reasons for such exclusion were claims that microbial toxicity tests were too difficult to interpret because of the high variability of microbial responses, uncertainty regarding the relevance of the various endpoints, and functional redundancy. Since the release of the first draft of the Eco-SSL Guidance document by the US Environmental Protection Agency in 2003, soil microbial toxicity testing and its use in ecological risk assessments have substantially improved. A wide range of standardized and nonstandardized methods became available for testing chemical toxicity to microbial functions in soil. Regulatory frameworks in the European Union and Australia have successfully incorporated microbial toxicity data into the derivation of soil threshold concentrations for ecological risk assessments. This article provides the 3-part rationale for including soil microbial processes in the development of soil clean-up values (SCVs): 1) presenting a brief overview of relevant test methods for assessing microbial functions in soil, 2) examining data sets for Cu, Ni, Zn, and Mo that incorporated soil microbial toxicity data into regulatory frameworks, and 3) offering recommendations on how to integrate the best available science into the method development for deriving site-specific SCVs that account for bioavailability of metals and metalloids in soil. Although the primary focus of this article is on the development of the approach for deriving SCVs for metals and metalloids in the United States, the recommendations provided in this article may also be applicable in other jurisdictions that aim at developing ecological soil threshold values for protection of microbial processes in contaminated soils. PMID:24376192

Microplastics as vectors for bioaccumulation of hydrophobic organic chemicals in the marine environment: A state-of-the-science review.

PubMed

Ziccardi, Linda M; Edgington, Aaron; Hentz, Karyn; Kulacki, Konrad J; Kane Driscoll, Susan

2016-07-01

A state-of-the-science review was conducted to examine the potential for microplastics to sorb hydrophobic organic chemicals (HOCs) from the marine environment, for aquatic organisms to take up these HOCs from the microplastics, and for this exposure to result in adverse effects to ecological and human health. Despite concentrations of HOCs associated with microplastics that can be orders of magnitude greater than surrounding seawater, the relative importance of microplastics as a route of exposure is difficult to quantify because aquatic organisms are typically exposed to HOCs from various compartments, including water, sediment, and food. Results of laboratory experiments and modeling studies indicate that HOCs can partition from microplastics to organisms or from organisms to microplastics, depending on experimental conditions. Very little information is available to evaluate ecological or human health effects from this exposure. Most of the available studies measured biomarkers that are more indicative of exposure than effects, and no studies showed effects to ecologically relevant endpoints. Therefore, evidence is weak to support the occurrence of ecologically significant adverse effects on aquatic life as a result of exposure to HOCs sorbed to microplastics or to wildlife populations and humans from secondary exposure via the food chain. More data are needed to fully understand the relative importance of exposure to HOCs from microplastics compared with other exposure pathways. Environ Toxicol Chem 2016;35:1667-1676. © 2016 SETAC. © 2016 SETAC.

Translational research in addiction: toward a framework for the development of novel therapeutics.

PubMed

Paterson, Neil E

2011-06-15

The development of novel substance use disorder (SUD) therapeutics is insufficient to meet the medical needs of a growing SUD patient population. The identification of translatable SUD models and tests is a crucial step in establishing a framework for SUD therapeutic development programs. The present review begins by identifying the clinical features of SUDs and highlights the narrow regulatory end-point required for approval of a novel SUD therapeutic. A conceptual overview of dependence is provided, followed by identification of potential intervention targets in the addiction cycle. The main components of the addiction cycle provide the framework for a discussion of preclinical models and their clinical analogs, all of which are focused on isolated behavioral end-points thought to be relevant to the persistence of compulsive drug use. Thus, the greatest obstacle to successful development is the gap between the multiplicity of preclinical and early clinical end-points and the regulatory end-point of sustained abstinence. This review proposes two pathways to bridging this gap: further development and validation of the preclinical extended access self-administration model; inclusion of secondary end-points comprising all of the measures highlighted in the present discussion in Phase 3 trials. Further, completion of the postdictive validation of analogous preclinical and clinical assays is of high priority. Ultimately, demonstration of the relevance and validity of a variety of end-points to the ultimate goal of abstinence will allow researchers to identify truly relevant therapeutic mechanisms and intervention targets, and establish a framework for SUD therapeutic development that allows optimal decision-making and resource allocation. 2011 Elsevier Inc. All rights reserved.

A new process for organizing assessments of social, economic, and environmental outcomes: case study of wildland fire management in the USA

Treesearch

Randall JF Bruins; Wayne R Jr. Munns; Stephen J Botti; Steve Brink; David Cleland; Larry Kapustka; Danny Lee; al. et

2010-01-01

Ecological risk assessments typically are organized using the processes of planning (a discussion among managers, stakeholders, and analysts to clarify ecosystem management goals and assessment scope) and problem formulation (evaluation of existing information to generate hypotheses about adverse ecological effects, select assessment endpoints, and develop an analysis...

A Viewpoint on Wearable Technology-Enabled Measurement of Wellbeing and Health-Related Quality of Life in Parkinson’s Disease

PubMed Central

van Uem, Janet M.T.; Isaacs, Tom; Lewin, Alan; Bresolin, Eros; Salkovic, Dina; Espay, Alberto J.; Matthews, Helen; Maetzler, Walter

2016-01-01

In this viewpoint, we discuss how several aspects of Parkinson’s disease (PD) – known to be correlated with wellbeing and health-related quality of life–could be measured using wearable devices (‘wearables’). Moreover, three people with PD (PwP) having exhaustive experience with using such devices write about their personal understanding of wellbeing and health-related quality of life, building a bridge between the true needs defined by PwP and the available methods of data collection. Rapidly evolving new technologies develop wearables that probe function and behaviour in domestic environments of people with chronic conditions such as PD and have the potential to serve their needs. Gathered data can serve to inform patient-driven management changes, enabling greater control by PwP and enhancing likelihood of improvements in wellbeing and health-related quality of life. Data can also be used to quantify wellbeing and health-related quality of life. Additionally these techniques can uncover novel more sensitive and more ecologically valid disease-related endpoints. Active involvement of PwP in data collection and interpretation stands to provide personally and clinically meaningful endpoints and milestones to inform advances in research and relevance of translational efforts in PD. PMID:27003779

The biological effects of ionising radiation on Crustaceans: A review.

PubMed

Fuller, Neil; Lerebours, Adélaïde; Smith, Jim T; Ford, Alex T

2015-10-01

Historic approaches to radiation protection are founded on the conjecture that measures to safeguard humans are adequate to protect non-human organisms. This view is disparate with other toxicants wherein well-developed frameworks exist to minimise exposure of biota. Significant data gaps for many organisms, coupled with high profile nuclear incidents such as Chernobyl and Fukushima, have prompted the re-evaluation of our approach toward environmental radioprotection. Elucidating the impacts of radiation on biota has been identified as priority area for future research within both scientific and regulatory communities. The crustaceans are ubiquitous in aquatic ecosystems, comprising greater than 66,000 species of ecological and commercial importance. This paper aims to assess the available literature of radiation-induced effects within this subphylum and identify knowledge gaps. A literature search was conducted pertaining to radiation effects on four endpoints as stipulated by a number of regulatory bodies: mortality, morbidity, reproduction and mutation. A major finding of this review was the paucity of data regarding the effects of environmentally relevant radiation doses on crustacean biology. Extremely few studies utilising chronic exposure durations or wild populations were found across all four endpoints. The dose levels at which effects occur was found to vary by orders of magnitude thus presenting difficulties in developing phyla-specific benchmark values and reference levels for radioprotection. Based on the limited data, mutation was found to be the most sensitive endpoint of radiation exposure, with mortality the least sensitive. Current phyla-specific dose levels and limits proposed by major regulatory bodies were found to be inadequate to protect species across a range of endpoints including morbidity, mutation and reproduction and examples are discussed within. These findings serve to prioritise areas for future research that will significantly advance understanding of radiation-induced effects in aquatic invertebrates and consequently enhance ability to predict the impacts of radioactive releases on the environment. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Predicting the sensitivity of populations from individual exposure to chemicals: the role of ecological interactions.

PubMed

Gabsi, Faten; Schäffer, Andreas; Preuss, Thomas G

2014-07-01

Population responses to chemical stress exposure are influenced by nonchemical, environmental processes such as species interactions. A realistic quantification of chemical toxicity to populations calls for the use of methodologies that integrate these multiple stress effects. The authors used an individual-based model for Daphnia magna as a virtual laboratory to determine the influence of ecological interactions on population sensitivity to chemicals with different modes of action on individuals. In the model, hypothetical chemical toxicity targeted different vital individual-level processes: reproduction, survival, feeding rate, or somatic growth rate. As for species interactions, predatory and competition effects on daphnid populations were implemented following a worst-case approach. The population abundance was simulated at different food levels and exposure scenarios, assuming exposure to chemical stress solely or in combination with either competition or predation. The chemical always targeted one vital endpoint. Equal toxicity-inhibition levels differently affected the population abundance with and without species interactions. In addition, population responses to chemicals were highly sensitive to the environmental stressor (predator or competitor) and to the food level. Results show that population resilience cannot be attributed to chemical stress only. Accounting for the relevant ecological interactions would reduce uncertainties when extrapolating effects of chemicals from individuals to the population level. Validated population models should be used for a more realistic risk assessment of chemicals. © 2014 SETAC.

Organism and population-level ecological models for ...

EPA Pesticide Factsheets

Ecological risk assessment typically focuses on animal populations as endpoints for regulatory ecotoxicology. Scientists at USEPA are developing models for animal populations exposed to a wide range of chemicals from pesticides to emerging contaminants. Modeled taxa include aquatic and terrestrial invertebrates, fish, amphibians, and birds, and employ a wide range of methods, from matrix-based projection models to mechanistic bioenergetics models and spatially explicit population models. not applicable

Surrogate outcomes are associated with low methodological quality of studies of rheumatoid arthritis treated with antitumour necrosis factor agents: a systematic review.

PubMed

Nobre, Moacyr Roberto Cuce; da Costa, Frnanda Marques

2012-02-01

Surrogate endpoints may be used as substitutes for, but often do not predict clinically relevant events. Objective To assess the methodological quality of articles that present their conclusions based on clinically relevant or surrogate outcomes in a systematic review of randomised trials and cohort studies of patients with rheumatoid arthritis treated with antitumour necrosis factor (TNF) agents. PubMed, Embase and Cochrane databases were searched. The Jadad score, the percentage of Consolidated Standards Of Reporting Trials (CONSORT) statement items adequately reported and levels-of-evidence (Center for Evidence-based Medicine, Oxford) were used in a descriptive synthesis. Among 88 articles appraised, 27 had surrogate endpoints, mainly radiographic, and 44 were duplicate publications; 74% of articles with surrogate and 39% of articles with clinical endpoints (p=0.006). Fewer articles with surrogate endpoints represented a high level of evidence (Level 1b, 33% vs 62%, p=0.037) and the mean percentage of CONSORT statement items met was also lower for articles with surrogate endpoints (62.5 vs 70.7, p=0.026). Although fewer articles with surrogate endpoints were randomised trials (63% vs 74%, p=0.307) and articles with surrogate endpoints had lower Jadad scores (3.0 vs 3.2, p=0.538), these differences were not statistically significant. Studies of anti-TNF agents that report surrogate outcomes are of lesser methodological quality. As such, inclusion of such studies in evidence syntheses may bias results.

Health-related quality-of-life as co-primary endpoint in randomized clinical trials in oncology.

PubMed

Fiteni, Frédéric; Pam, Alhousseiny; Anota, Amélie; Vernerey, Dewi; Paget-Bailly, Sophie; Westeel, Virginie; Bonnetain, Franck

2015-01-01

Overall survival (OS) has been considered as the most relevant primary endpoint but trials using OS often require large numbers of patients and long-term follow-up. Therefore composite endpoints, which are assessed earlier, are frequently used as primary endpoint but suffer from important limitations specially a lack of validation as surrogate of OS. Therefore, Health-related quality of life (HRQoL) could be considered as an outcome to judge efficacy of a treatment. An alternative approach would be to combine HRQoL with composite endpoints as co-primary endpoint to ensure a clinical benefit for patients of a new therapy. The decision rules of such design, the procedure to control the Type I error and the determination of sample size remain questions to debate. Here, we discusses HRQoL as co-primary endpoints in randomized clinical trials in oncology and provide some solutions to promote such design.

The effects of repeated nitroglycerin administrations in rats; modeling migraine-related endpoints and chronification.

PubMed

Harris, Hannah M; Carpenter, Jessica M; Black, Jonathan R; Smitherman, Todd A; Sufka, Kenneth J

2017-06-01

Rodent models typically use a single nitroglycerin injection to induce migraine, yet migraine in clinical populations presents as recurrent episodes. Further, these models quantify behavioral endpoints that do not align with the clinical features of episodic migraine or migraine chronification and therefore may limit translational relevance. Rats received 5 nitroglycerin (10mg/kg/2ml), propylene glycol/ethanol vehicle, or saline injections every third day over 15days. Behavioral endpoints were assessed 110min post nitroglycerin administration and included time spent light/dark chambers for photophobia as well as activity, facial pain expressions, and tactile allodynia. Animals administered nitroglycerin displayed photophobia, decreased activity, and increased facial pain expression. Similar alterations in photophobia and activity were seen in the vehicle treated animals, but these tended to diminish by the 4th or 5th injection. The presentation of spontaneous tactile allodynia was observed in the nitroglycerin group by the 5th episode. Most NTG migraine models entail a single NTG administration and quantification of evoked allodynia. This paradigm employs recurring NTG episodes and clinically-relevant measures of photophobia, hypoactivity and facial grimace endpoints as well as introduces a novel arena apparatus to quantify spontaneous allodynia. This repeated NTG procedure and endpoint measures aligns with the frequency and clinical presentation of episodic migraine and its chronification, respectively. Further, propylene glycol ethanol vehicle contributes to migraine endpoints. Copyright © 2017 Elsevier B.V. All rights reserved.

Applying Theory across Settings, Behaviors and Populations: Translational Challenges and Opportunities

PubMed Central

Mermelstein, Robin J.; Revenson, Tracey A.

2013-01-01

Basic social psychological theories have much to contribute to our understanding of health problems and health-related behaviors and may provide potential avenues for intervention development. However, for these theories to have broader reach and applicability to the field of health psychology, more work needs to be done in integrating contexts into these theories and addressing more specifically their application across settings, behaviors, and populations. We argue that integration of these theories into a broader multi-disciplinary and multi-level ecological framework is needed to enhance their translation into real-world applications. To enhance this translation, we make several recommendations, including breaking down silos between disciplinary perspectives and enhancing bidirectional communication and translation; analyzing boundary conditions of theories; expanding research approaches to move outside the laboratory and maintain a focus on external validity; and conducting efficacy testing of theories with meaningful, relevant endpoints. PMID:23646843

Applying theory across settings, behaviors, and populations: translational challenges and opportunities.

PubMed

Mermelstein, Robin J; Revenson, Tracey A

2013-05-01

Basic social psychological theories have much to contribute to our understanding of health problems and health-related behaviors and may provide potential avenues for intervention development. However, for these theories to have broader reach and applicability to the field of health psychology, more work needs to be done in integrating contexts into these theories and addressing more specifically their application across settings, behaviors, and populations. We argue that integration of these theories into a broader multidisciplinary and multilevel ecological framework is needed to enhance their translation into real-world applications. To enhance this translation, we make several recommendations, including breaking down silos between disciplinary perspectives and enhancing bidirectional communication and translation; analyzing boundary conditions of theories; expanding research approaches to move outside the laboratory and maintain a focus on external validity; and conducting efficacy testing of theories with meaningful, relevant endpoints. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Aquatic Life Benchmarks and Ecological Risk Assessments for Registered Pesticides

EPA Pesticide Factsheets

Each Aquatic Life Benchmark is based on the most sensitive, scientifically acceptable toxicity endpoint available to EPA for a given taxon (for example, freshwater fish) of all scientifically acceptable toxicity data available to EPA.

Some controversial multiple testing problems in regulatory applications.

PubMed

Hung, H M James; Wang, Sue-Jane

2009-01-01

Multiple testing problems in regulatory applications are often more challenging than the problems of handling a set of mathematical symbols representing multiple null hypotheses under testing. In the union-intersection setting, it is important to define a family of null hypotheses relevant to the clinical questions at issue. The distinction between primary endpoint and secondary endpoint needs to be considered properly in different clinical applications. Without proper consideration, the widely used sequential gate keeping strategies often impose too many logical restrictions to make sense, particularly to deal with the problem of testing multiple doses and multiple endpoints, the problem of testing a composite endpoint and its component endpoints, and the problem of testing superiority and noninferiority in the presence of multiple endpoints. Partitioning the null hypotheses involved in closed testing into clinical relevant orderings or sets can be a viable alternative to resolving the illogical problems requiring more attention from clinical trialists in defining the clinical hypotheses or clinical question(s) at the design stage. In the intersection-union setting there is little room for alleviating the stringency of the requirement that each endpoint must meet the same intended alpha level, unless the parameter space under the null hypothesis can be substantially restricted. Such restriction often requires insurmountable justification and usually cannot be supported by the internal data. Thus, a possible remedial approach to alleviate the possible conservatism as a result of this requirement is a group-sequential design strategy that starts with a conservative sample size planning and then utilizes an alpha spending function to possibly reach the conclusion early.

Low-Light Dependence of the Magnetic Field Effect on Cryptochromes: Possible Relevance to Plant Ecology

PubMed Central

Vanderstraeten, Jacques; Gailly, Philippe; Malkemper, E. Pascal

2018-01-01

Various responses to static magnetic fields (MF) have been reported in plants, and it has been suggested that the geomagnetic field influences plant physiology. Accordingly, diverse mechanisms have been proposed to mediate MF effects in plants. The currently most probable sensor candidates are cryptochromes (Cry) which are sensitive to submillitesla MF. Here, we propose a quantitative approach of the MF effect on Cry depending on light intensity, and try to link it to a possible functional role for magnetic sensitivity in plants. Based on a theoretical evaluation and on a review of relevant data on Arabidopsis thaliana Cry 1, we point out that the MF effect on the signaling state of Cry, as well as the possible consequences of that effect on certain phenotypes (growth in particular) show parallel dependences on light intensity, being most prominent at low light levels. Based on these findings, we propose that Cry magnetosensitivity in plants could represent an ecological adaptation which regulates the amount of Cry signaling state under low light conditions. That hypothesis would preferentially be tested by studying sensitive and specific endpoints, such as the expression of clock proteins that are downregulated by Cry, but under light intensities lower than those used so far. Finally, we highlight that the low-light dependence of the MF effect described here could also apply to light-dependent functions of animal Cry, in particular magnetoreception which, from the present evaluation, would be based on the magnetic sensitivity of the photoreduction reaction, like in plants. PMID:29491873

The influence of insecticide exposure and environmental stimuli on the movement behaviour and dispersal of a freshwater isopod.

PubMed

Augusiak, Jacqueline; Van den Brink, Paul J

2016-09-01

Behaviour links physiological function with ecological processes and can be very sensitive towards environmental stimuli and chemical exposure. As such, behavioural indicators of toxicity are well suited for assessing impacts of pesticides at sublethal concentrations found in the environment. Recent developments in video-tracking technologies offer the possibility of quantifying behavioural patterns, particularly locomotion, which in general has not been studied and understood very well for aquatic macroinvertebrates to date. In this study, we aim to determine the potential effects of exposure to two neurotoxic pesticides with different modes of action at different concentrations (chlorpyrifos and imidacloprid) on the locomotion behaviour of the water louse Asellus aquaticus. We compare the effects of the different exposure regimes on the behaviour of Asellus with the effects that the presence of food and shelter exhibit to estimate the ecological relevance of behavioural changes. We found that sublethal pesticide exposure reduced dispersal distances compared to controls, whereby exposure to chlorpyrifos affected not only animal activity but also step lengths while imidacloprid only slightly affected step lengths. The presence of natural cues such as food or shelter induced only minor changes in behaviour, which hardly translated to changes in dispersal potential. These findings illustrate that behaviour can serve as a sensitive endpoint in toxicity assessments. However, under natural conditions, depending on the exposure concentration, the actual impacts might be outweighed by environmental conditions that an organism is subjected to. It is, therefore, of importance that the assessment of toxicity on behaviour is done under relevant environmental conditions.

Assessing ecological risks to the fish community from residual coal fly ash in Watts Bar Reservoir, Tennessee

DOE PAGES

Rigg, David K.; Wacksman, Mitch N.; Iannuzzi, Jacqueline; ...

2014-12-18

For this research, extensive site-specific biological and environmental data were collected to support an evaluation of risks to the fish community in Watts Bar Reservoir from residual ash from the December 2008 Tennessee Valley Authority (TVA) Kingston ash release. This paper describes the approach used and results of the risk assessment for the fish community, which consists of multiple measurement endpoints (measures of exposure and effects) for fish. The lines of evidence included 1) comparing postspill annual fish community assessments with nearby prespill data and data from other TVA reservoirs, 2) evaluating possible effects of exposures of fish eggs andmore » larval fish to ash in controlled laboratory toxicity tests, 3) evaluating reproductive competence of field-exposed fish, 4) assessing individual fish health through physical examination, histopathology, and blood chemistry, 5) comparing fish tissue concentrations with literature-based critical body residues, and 6) comparing concentrations of ash-related contaminants in surface waters with US Environmental Protection Agency's (USEPA) Ambient Water Quality Standards for Fish and Aquatic Life. These measurement endpoints were treated as independent lines of evidence that were integrated into an overall weight-of-evidence estimate of risk to the fish community. Collectively, the data and analysis presented here indicate that ash and ash-related constituents pose negligible risks to the fish communities in Watts Bar Reservoir. This conclusion contradicts the predictions by some researchers immediately following the ash release of devastating effects on the aquatic ecology of Watts Bar Reservoir. The information presented in this article reaffirms the wisdom of carefully evaluating the evidence before predicting probable ecological effects of a major event such as the TVA Kingston ash release. Lastly, this study demonstrates that a thorough and detailed investigation using multiple measurement endpoints is needed to properly evaluate ecological effects.« less

Assessing ecological risks to the fish community from residual coal fly ash in Watts Bar Reservoir, Tennessee

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rigg, David K.; Wacksman, Mitch N.; Iannuzzi, Jacqueline

For this research, extensive site-specific biological and environmental data were collected to support an evaluation of risks to the fish community in Watts Bar Reservoir from residual ash from the December 2008 Tennessee Valley Authority (TVA) Kingston ash release. This paper describes the approach used and results of the risk assessment for the fish community, which consists of multiple measurement endpoints (measures of exposure and effects) for fish. The lines of evidence included 1) comparing postspill annual fish community assessments with nearby prespill data and data from other TVA reservoirs, 2) evaluating possible effects of exposures of fish eggs andmore » larval fish to ash in controlled laboratory toxicity tests, 3) evaluating reproductive competence of field-exposed fish, 4) assessing individual fish health through physical examination, histopathology, and blood chemistry, 5) comparing fish tissue concentrations with literature-based critical body residues, and 6) comparing concentrations of ash-related contaminants in surface waters with US Environmental Protection Agency's (USEPA) Ambient Water Quality Standards for Fish and Aquatic Life. These measurement endpoints were treated as independent lines of evidence that were integrated into an overall weight-of-evidence estimate of risk to the fish community. Collectively, the data and analysis presented here indicate that ash and ash-related constituents pose negligible risks to the fish communities in Watts Bar Reservoir. This conclusion contradicts the predictions by some researchers immediately following the ash release of devastating effects on the aquatic ecology of Watts Bar Reservoir. The information presented in this article reaffirms the wisdom of carefully evaluating the evidence before predicting probable ecological effects of a major event such as the TVA Kingston ash release. Lastly, this study demonstrates that a thorough and detailed investigation using multiple measurement endpoints is needed to properly evaluate ecological effects.« less

Effects of water scarcity and chemical pollution in aquatic ecosystems: State of the art.

PubMed

Arenas-Sánchez, Alba; Rico, Andreu; Vighi, Marco

2016-12-01

Water scarcity is an expanding climate and human related condition, which drives and interacts with other stressors in freshwater ecosystems such as chemical pollution. In this study we provide an overview of the existing knowledge regarding the chemical fate, biological dynamics and the ecological risks of chemicals under water scarcity conditions. We evaluated a total of 15 studies dealing with the combined effects of chemicals and water scarcity under laboratory conditions and in the field. The results of these studies have been elaborated in order to evaluate additive, synergistic or antagonistic responses of the studied endpoints. As a general rule, it can be concluded that, in situations of water scarcity, the impacts of extreme water fluctuations are much more relevant than those of an additional chemical stressor. Nevertheless, the presence of chemical pollution may result in exacerbated ecological risks in some particular cases. We conclude that further investigations on this topic would take advantage on the focus on some specific issues. Experimental (laboratory and model ecosystem) studies should be performed on different biota groups and life stages (diapausing eggs, immature stages), with particular attention to those including traits relevant for the adaptation to water scarcity. More knowledge on species adaptations and recovery capacity is essential to predict community responses to multiple stressors and to assess the community vulnerability. Field studies should be performed at different scales, particularly in lotic systems, in order to integrate different functional dynamics of the river ecosystem. Combining field monitoring and experimental studies would be the best option to reach more conclusive, causal relationships on the effects of co-occurring stressors. Contribution of these studies to develop ecological models and scenarios is also suggested as an improvement for the prospective aquatic risk assessment of chemicals in (semi-)arid areas. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomarkers as a tool to assess effects of chromium (VI): comparison of responses in zebrafish early life stages and adults.

PubMed

Domingues, Inês; Oliveira, Rhaul; Lourenço, Joana; Grisolia, Cesar Koppe; Mendo, Sónia; Soares, A M V M

2010-09-01

The present work aims to compare the sensitivity of embryos and adult zebrafish to chromium (VI) (as potassium dichromate) focusing on biomarkers (cholinesterase, glutathione S-transferase and lactate dehydrogenase) as endpoints. Zebrafish eggs showed less sensitivity to Cr (VI) (96 h-LC50=145.7 mg/L) than adults (96 h-LC50=39.4 mg/L) probably due to the protective action of the chorion. However, biomarkers were much more responsive in larvae than in adults and gave clear indications about Cr (VI) mode of action: it seems to be neurotoxic (inhibited cholinesterase), to inhibit glutathione S-transferase activity and to interfere with cellular metabolic activity (changes in lactate dehydrogenase activity) in larvae. In adults, only glutathione S-transferase was responsive, showing a clear inhibition. The responsiveness of the analyzed biomarkers in larvae reinforces the idea of the usefulness of early life stage assays in the assessment of chemicals effects. Moreover, early life stage assays also contributed with relevant information regarding anomalies in larvae development and behavior. Further research should focus on the use of biomarkers to assess long term effects which are ecologically more relevant. Copyright (c) 2010 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fitzpatrick, L.C.; Goven, A.J.; Muratti-Ortiz, J.F.

Earthworms are ideal soil organisms for use in terrestrial ecotoxicology. As such, several earthworm protocols have been developed for testing toxic potential of chemicals and contaminated soils. Of these, the 48-h filter paper contact (FP) and the 14-d artificial soil exposure (AS) protocols, using mortality (LC50) as the toxic endpoint and Eisenia fetida as the test species, have received the most attention, with the latter being adopted by both OECD and EEC in Europe and the Environmental Protection Agency (USEPA) in the United States. Although the FP technique, adopted by EEC, provides for inexpensive reproducible toxicity screening for chemicals (i.e.more » establishing relative toxicities), it has been criticized for lacking the ecotoxicological relevance of the AS protocol. Choice of earthworm species for laboratory testing also has been controversial. The manure worm, E. fetida, is criticized for not being sufficiently sensitive to chemicals or representative of {open_quotes}typical{close_quotes} earthworms. Lumbricus terrestris and Apporectodea caliginosa have been suggested as more sensitive and ecologically relevant earthworms by Dean-Ross and Martin, respectively. This paper compares the AS and FP protocols in assessing toxicity of cadminum to L. terrestris and E. fetida using LC50s and LC50s. 19 refs., 2 tabs.« less

Glyphosate and Dicamba Inhibit Flowering of Native Willamette Valley Plants

EPA Science Inventory

Successful flowering is essential for reproduction of native plants and production of food for herbivores. It is also an important alternative endpoint for assessment of ecological risks from chemical stressors such as herbicides. We evaluated flowering phenology after herbicide...

Adverse Outcome Pathways and Extrapolation Tools to Advance the Three Rs in Ecotoxicology

EPA Science Inventory

Adverse outcome pathways (AOPs) are conceptual frameworks for identifying and organizing predictive and causal linkages between cellular-level responses and endpoints conventionally considered in ecological risk assessment (e.g., effects on survival, growth/development, and repro...

METABOLOMICS IN SMALL FISH TOXICOLOGY AND ECOLOGICAL RISK ASSESSMENTS

EPA Science Inventory

The US EPA is tasked with protecting not only humans, but also ecosystems from potentially harmful effects of chemical pollutants. Although lagging behind applications targeted to human endpoints, metabolomics offers great potential in ecotoxicology. Indeed, the advantages of met...

Tributyltin induces premature hatching and reduces locomotor activity in zebrafish (Danio rerio) embryos/larvae at environmentally relevant levels.

PubMed

Liang, Xuefang; Souders, Christopher L; Zhang, Jiliang; Martyniuk, Christopher J

2017-12-01

Tributyltin (TBT) is an organotin compound that is the active ingredient of many biocides and antifouling agents. In addition to its well established role as an endocrine disruptor, TBT is also associated with adverse effects on the nervous system and behavior. In this study, zebrafish (Danio rerio) embryos were exposed to environmentally relevant concentrations of TBT (0.01, 0.1, 1 nM) to determine how low levels affected development and behavior. Fish exposed to 1 nM TBT hatched earlier when compared to controls. Following a 96-h exposure, total swimming distance, velocity, and activity of zebrafish larvae were reduced compared to controls. To identify putative mechanisms for these altered endpoints, we assessed embryo bioenergetics and gene expression. We reasoned that the accelerated hatch time could be related to ATP production and energy, thus embryos were exposed to TBT for 24 and 48-h exposure prior to hatch. There were no differences among groups for endpoints related to bioenergetics (i.e. basal, ATP-dependent, and maximal respiration). To address mechanisms related to changes in behavioral activity, we measured transcripts associated with muscle function (myf6, myoD, and myoG) and dopamine signaling (th, dat, dopamine receptors) as dopamine regulates behavior. No transcript was altered in expression by TBT in larvae, suggesting that other mechanisms exist that may explain changes in higher level endpoints. These results suggest that endpoints related to the whole animal (i.e. timing of hatch and locomotor behavior) are more sensitive to environmentally-relevant concentrations of TBT compared to the molecular and metabolic endpoints examined here. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diatoms to human uses: linking nitrogen deposition, aquatic eutrophication, and ecosystem services

DOE PAGES

Rhodes, Charles; Bingham, Andrew; Heard, Andrea M.; ...

2017-07-24

Nitrogen (N) loading to aquatic ecosystems can lead to eutrophication, changing the ecosystem within a waterbody, including primary productivity, water clarity, and food web dynamics. Nutrient loading often first affects the primary productivity of aquatic systems through shifts in phytoplankton communities. However, ecologically important changes in phytoplankton are often not relatable to the general public—whose behavior would need to change to alter patterns of nutrient loading. Therefore, we use the STressor–Ecological Production function–final ecosystem Services Framework to develop 154 chains that link changes in biological indicators of aquatic eutrophication (a shift in phytoplankton community) to final ecosystem services that peoplemore » use or appreciate. We identify 13 ecological production functions (EPF) within three different ecosystems (alpine lakes, lakes, and estuaries) that connect changes in phytoplankton and algae to ecological endpoints that the general public and policy makers can appreciate. Using the Final Ecosystem Goods and Services Classification System, we identify 18 classes of human beneficiaries that potentially will be impacted by a change in one of these endpoints. We further assign strength-of-science scores to each link within the EPFs for the 154 chains according to how well each link is supported by current peer-reviewed literature. By identifying many pathways through which excess N loading in U.S. surface waters can affect ecosystems and ultimately the beneficiaries of ecosystem services, this work intends to draw attention to gaps in empirical ecological literature that constrain understanding of the magnitude of effects that excess N loading can have on human well-being. Here, results highlight the importance of intersections between the natural and social sciences when managers and policy makers evaluate impacts from ecological stressors. A balance between knowledgeable specialists proved key to applying this approach and will continue to remain important.« less

Diatoms to human uses: linking nitrogen deposition, aquatic eutrophication, and ecosystem services

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rhodes, Charles; Bingham, Andrew; Heard, Andrea M.

Nitrogen (N) loading to aquatic ecosystems can lead to eutrophication, changing the ecosystem within a waterbody, including primary productivity, water clarity, and food web dynamics. Nutrient loading often first affects the primary productivity of aquatic systems through shifts in phytoplankton communities. However, ecologically important changes in phytoplankton are often not relatable to the general public—whose behavior would need to change to alter patterns of nutrient loading. Therefore, we use the STressor–Ecological Production function–final ecosystem Services Framework to develop 154 chains that link changes in biological indicators of aquatic eutrophication (a shift in phytoplankton community) to final ecosystem services that peoplemore » use or appreciate. We identify 13 ecological production functions (EPF) within three different ecosystems (alpine lakes, lakes, and estuaries) that connect changes in phytoplankton and algae to ecological endpoints that the general public and policy makers can appreciate. Using the Final Ecosystem Goods and Services Classification System, we identify 18 classes of human beneficiaries that potentially will be impacted by a change in one of these endpoints. We further assign strength-of-science scores to each link within the EPFs for the 154 chains according to how well each link is supported by current peer-reviewed literature. By identifying many pathways through which excess N loading in U.S. surface waters can affect ecosystems and ultimately the beneficiaries of ecosystem services, this work intends to draw attention to gaps in empirical ecological literature that constrain understanding of the magnitude of effects that excess N loading can have on human well-being. Here, results highlight the importance of intersections between the natural and social sciences when managers and policy makers evaluate impacts from ecological stressors. A balance between knowledgeable specialists proved key to applying this approach and will continue to remain important.« less

. Ecological conceptual models: a framework and case study on ecosystem management for South Florida sustainability

USGS Publications Warehouse

Gentile, J.H.; Harwell, M.A.; Cropper, W.; Harwell, C. C.; DeAngelis, Donald L.; Davis, S.; Ogden, J.C.; Lirman, D.

2001-01-01

The Everglades and South Florida ecosystems are the focus of national and international attention because of their current degraded and threatened state. Ecological risk assessment, sustainability and ecosystem and adaptive management principles and processes are being used nationally as a decision and policy framework for a variety of types of ecological assessments. The intent of this study is to demonstrate the application of these paradigms and principles at a regional scale. The effects-directed assessment approach used in this study consists of a retrospective, eco-epidemiological phase to determine the causes for the current conditions and a prospective predictive risk-based assessment using scenario analysis to evaluate future options. Embedded in these assessment phases is a process that begins with the identification of goals and societal preferences which are used to develop an integrated suite of risk-based and policy relevant conceptual models. Conceptual models are used to illustrate the linkages among management (societal) actions, environmental stressors, and societal/ecological effects, and provide the basis for developing and testing causal hypotheses. These models, developed for a variety of landscape units and their drivers, stressors, and endpoints, are used to formulate hypotheses to explain the current conditions. They are also used as the basis for structuring management scenarios and analyses to project the temporal and spatial magnitude of risk reduction and system recovery. Within the context of recovery, the conceptual models are used in the initial development of performance criteria for those stressors that are determined to be most important in shaping the landscape, and to guide the use of numerical models used to develop quantitative performance criteria in the scenario analysis. The results will be discussed within an ecosystem and adaptive management framework that provides the foundation for decision making.

Biological responses of two marine organisms of ecological relevance to on-going ocean acidification and global warming.

PubMed

Gomiero, A; Bellerby, R G J; Manca Zeichen, M; Babbini, L; Viarengo, A

2018-05-01

Recently, there has been a growing concern that climate change may rapidly and extensively alter global ecosystems with unknown consequences for terrestrial and aquatic life. While considerable emphasis has been placed on terrestrial ecology consequences, aquatic environments have received relatively little attention. Limited knowledge is available on the biological effects of increments of seawater temperature and pH decrements on key ecological species, i.e., primary producers and/or organisms representative of the basis of the trophic web. In the present study, we addressed the biological effects of global warming and ocean acidification on two model organisms, the microbenthic marine ciliate Euplotes crassus and the green alga Dunaliella tertiocleta using a suite of high level ecological endpoint tests and sub-lethal stress measures. Organisms were exposed to combinations of pH and temperature (TR1: 7.9 [pH], 25.5 °C and TR2: 7.8 [pH], 27,0 °C) simulating two possible environmental scenarios predicted to occur in the habitats of the selected species before the end of this century. The outcomes of the present study showed that the tested scenarios did not induce a significant increment of mortality on protozoa. Under the most severe exposure conditions, sub-lethal stress indices show that pH homeostatic mechanisms have energetic costs that divert energy from essential cellular processes and functions. The marine protozoan exhibited significant impairment of the lysosomal compartment and early signs of oxidative stress under these conditions. Similarly, significant impairment of photosynthetic efficiency and an increment in lipid peroxidation were observed in the autotroph model organism held under the most extreme exposure condition tested. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ecological conceptual models: a framework and case study on ecosystem management for South Florida sustainability.

PubMed

Gentile, J H; Harwell, M A; Cropper, W; Harwell, C C; DeAngelis, D; Davis, S; Ogden, J C; Lirman, D

2001-07-02

The Everglades and South Florida ecosystems are the focus of national and international attention because of their current degraded and threatened state. Ecological risk assessment, sustainability, and ecosystem and adaptive management principles and processes are being used nationally as a decision and policy framework for a variety of types of ecological assessments. The intent of this study is to demonstrate the application of these paradigms and principles at a regional scale. The effects-directed assessment approach used in this study consists of a retrospective, eco-epidemiological phase to determine the causes for the current conditions and a prospective predictive risk-based assessment using scenario analysis to evaluate future options. Embedded in these assessment phases is a process that begins with the identification of goals and societal preferences which are used to develop an integrated suite of risk-based and policy relevant conceptual models. Conceptual models are used to illustrate the linkages among management (societal) actions, environmental stressors, and societal/ecological effects, and provide the basis for developing and testing causal hypotheses. These models, developed for a variety of landscape units and their drivers, stressors, and endpoints, are used to formulate hypotheses to explain the current conditions. They are also used as the basis for structuring management scenarios and analyses to project the temporal and spatial magnitude of risk reduction and system recovery. Within the context of recovery, the conceptual models are used in the initial development of performance criteria for those stressors that are determined to be most important in shaping the landscape, and to guide the use of numerical models used to develop quantitative performance criteria in the scenario analysis. The results will be discussed within an ecosystem and adaptive management framework that provides the foundation for decision making.

Effect-Based Tools for Monitoring and Predicting the Ecotoxicological Effects of Chemicals in the Aquatic Environment

PubMed Central

Connon, Richard E.; Geist, Juergen; Werner, Inge

2012-01-01

Ecotoxicology faces the challenge of assessing and predicting the effects of an increasing number of chemical stressors on aquatic species and ecosystems. Herein we review currently applied tools in ecological risk assessment, combining information on exposure with expected biological effects or environmental water quality standards; currently applied effect-based tools are presented based on whether exposure occurs in a controlled laboratory environment or in the field. With increasing ecological relevance the reproducibility, specificity and thus suitability for standardisation of methods tends to diminish. We discuss the use of biomarkers in ecotoxicology including ecotoxicogenomics-based endpoints, which are becoming increasingly important for the detection of sublethal effects. Carefully selected sets of biomarkers allow an assessment of exposure to and effects of toxic chemicals, as well as the health status of organisms and, when combined with chemical analysis, identification of toxicant(s). The promising concept of “adverse outcome pathways (AOP)” links mechanistic responses on the cellular level with whole organism, population, community and potentially ecosystem effects and services. For most toxic mechanisms, however, practical application of AOPs will require more information and the identification of key links between responses, as well as key indicators, at different levels of biological organization, ecosystem functioning and ecosystem services. PMID:23112741

Evaluating the Effectiveness of Passive Sampling as a Surrogate for Organism Bioaccumulation.

EPA Science Inventory

Measurement of hydrophobic organic contaminants (HOCs) and the subsequent evaluation of their ecological and human health risks are common endpoints in aquatic environmental monitoring. Due to their hydrophobicity, many anthropogenic HOCs will partition from the water into organi...

Evaluating the Effectiveness of Passive Sampling as a Surrogate for Organism Bioaccumulation

EPA Science Inventory

Measurement of hydrophobic organic contaminants (HOCs) and the subsequent evaluation of their ecological and human health risks are common endpoints in aquatic environmental monitoring. Due to their hydrophobicity, many anthropogenic HOCs will partition from the water into organi...

Molecular Endpoints and Mixtures of EDCs in Fish

EPA Science Inventory

Microarray technology is a relatively novel tool in ecotoxicology and is beginning to be used for exposure and/or hazard characterization for ecological risk assessment. To develop a basis for this type of analysis, fathead minnows (Pimephales promelas) were treated with two bin...

EPA'S REGIONAL VULNERABILITY ASSESSMENT PROGRAM: TOOLS TO FACILITATE REGIONAL TO LOCAL DECISION-MAKING

EPA Science Inventory

EPA's Regional Vulnerability Assessment (ReVA) program is developing and testing approaches to conducting comparative environmental risk assessments at the regional scale, considering impacts to ecological human, and fiscal health endpoints. It seeks an objective and quantifiable...

Ecologically-based clean-up criteria for nitroaromatic explosives using toxicity test results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duh, D.; Roberts, B.; Buzgo, S.

1995-12-31

A former trinitrotoluene (TNT) production and storage facility was the focus of a Remedial Investigation (RI). Contaminants identified during the RI included 2,4-dinitrotoluene (DNT), 2,6-DNT, and 2,4,6-TNT, PCBs, arsenic, lead and chromium. The Conceptual Site Model determined there to be several complete exposure pathways. One of these identified a route by which soil invertebrate communities could be affected through dermal contact and ingestion of soil contaminants. Maintenance of the soil invertebrate community was chosen as the assessment endpoints for this pathway in the Ecological Risk Assessment. The corresponding measurement endpoint was survival of earthworms in 14-day toxicity tests in whichmore » they were exposed to site soils. Seven surficial soil samples were collected from Areas of Concern. Each sample was evaluated for acute toxicity to earthworms using standard USEPA protocols. Chemical concentrations were also measured. An artificial soil was used as the control and diluent to establish the Lethal Concentration (LC{sub 50}) of the test soils to earthworms. From the toxicity test results and the corresponding chemical analysis, a matrix of toxicity and contaminant levels was developed. This table was used to determine a concentration of each contaminant at which no acute lethality would be expected. Lower bounds to the chemical specific LC{sub 50} values were determined and, based on sample-specific toxicity units, appropriate LC{sub 50} values were derived (333 mg/kg 2,4-DNT, 182 mg/kg 2,6-DNT, and 1960 mg/kg 2,4,6TNT). Extrapolation of this level to a chronic No Observable Adverse Effect Level (NOAEL) provided a means of proposing site-specific ecologically based clean-up criteria for the constituents of concern which would be protective of the chosen assessment endpoint.« less

Biomarkers and Surrogate Endpoints in Drug Development: A European Regulatory View.

PubMed

Wickström, Kerstin; Moseley, Jane

2017-05-01

To give a European regulatory overview of the requirements on and the use of biomarkers or surrogate endpoints in the development of drugs for ocular disease. Definitions, methods to validate new markers, and circumstances where surrogate endpoints can be appropriate are summarized. The key endpoints that have been used in registration studies so far are based on visual acuity, signs, and symptoms, or on surrogate endpoints. In some ocular conditions, established outcome measures such as those based on visual acuity or visual field are not feasible (as with slowly progressing diseases), or lack relevance (e.g., when central visual acuity may be preserved even though the patient is legally blind owing to a severely restricted visual field, or vice versa). There are several ocular conditions for which there is an unmet medical need. In some of these conditions, surrogate endpoints as well as new clinical endpoints are needed to help speed up patient access to new medicines. Interaction with European regulators through the pathway specific for the development of biomarkers or novel methods is encouraged.

DECISION SUPPORT TOOL FOR EVALUATING VULNERABILITY TO HAZARDOUS AIR POLLUTANTS IN THE SOUTHEAST

EPA Science Inventory

Valued ecological endpoints such as threatened and endangered species and critical habitat are often evaluated for proximate impacts such as nearby development and direct impacts such as logging. Exposure to atmospheric pollutants can exacerbate the affects on these already vuln...

DETECTING BENTHIC COMMUNITY DIFFERENCES: INFLUENCE OF STATISTICAL INDEX AND SEASON

EPA Science Inventory

An accurate assessment of estuarine condition is critical to determining whether there has been a change from baseline or 'natural' conditions; benthic communities are routinely used as an ecological endpoint to make this assessment. We addressed two issues which arise when attem...

Simulated developmental and reproductive impacts on amphibian populations and implications for assessing long-term effects

EPA Science Inventory

Fish endpoints measured in early life stage toxicity tests are often used as representative of larval amphibian sensitivity in Ecological Risk Assessment (ERA). This application potentially overlooks the impact of developmental delays on amphibian metamorphosis, and thereby red...

Detection of Bordetella pertussis from Clinical Samples by Culture and End-Point PCR in Malaysian Patients.

PubMed

Ting, Tan Xue; Hashim, Rohaidah; Ahmad, Norazah; Abdullah, Khairul Hafizi

2013-01-01

Pertussis or whooping cough is a highly infectious respiratory disease caused by Bordetella pertussis. In vaccinating countries, infants, adolescents, and adults are relevant patients groups. A total of 707 clinical specimens were received from major hospitals in Malaysia in year 2011. These specimens were cultured on Regan-Lowe charcoal agar and subjected to end-point PCR, which amplified the repetitive insertion sequence IS481 and pertussis toxin promoter gene. Out of these specimens, 275 were positive: 4 by culture only, 6 by both end-point PCR and culture, and 265 by end-point PCR only. The majority of the positive cases were from ≤3 months old patients (77.1%) (P < 0.001). There was no significant association between type of samples collected and end-point PCR results (P > 0.05). Our study showed that the end-point PCR technique was able to pick up more positive cases compared to culture method.

[Structural endpoints for glaucoma studies].

PubMed

Popa-Cherechenau, A; Schmidl, D; Garhöfer, G; Schmetterer, L

2018-03-06

Structural endpoints have been discussed as surrogate endpoints for the approval of neuroprotective drugs in glaucoma. Is the evidence strong enough to establish structural endpoints as surrogate endpoints? Review of current understanding between structure and function in glaucoma. The introduction of optical coherence tomography has revolutionized imaging in glaucoma patients. Clinically either the nerve fiber layer thickness can be measured along a circle centered in the optic nerve head or the ganglion cell layer thickness can be assessed in the macular region, the latter being quantified in combination with other inner retinal layers. On a microscopic level there is a strong correlation between structural and functional loss but this relation can only partially be described with currently available clinical methods. This is particularly true for longitudinal course of the disease in glaucoma patients. Novel imaging techniques that are not yet used clinically may have the potential to increase our understanding between structure and function in glaucoma but further research in this field is required. The current evidence does not allow the establishment of structural endpoints as surrogate endpoints for phase 3 studies in glaucoma. Neuroprotective drugs have to be approved on the basis of visual field data because this is the patient-relevant endpoint. Structural endpoints can, however, play an important role in phase 2 and proof of concept studies.

Responsiveness of efficacy endpoints in clinical trials with over the counter analgesics for headache.

PubMed

Aicher, Bernhard; Peil, Hubertus; Peil, Barbara; Diener, Hans-Christoph

2012-10-01

To quantify and compare the responsiveness within the meaning of clinical relevance of efficacy endpoints in a clinical trial with over the counter (OTC) analgesics for headache. Efficacy endpoints and observed differences in clinical trials need to be clinically meaningful and mirror the change in the clinical status of a patient. This must be demonstrated for the specific disease indication and the particular patient population based on the application of treatments with proven efficacy. Patient's global efficacy assessment during two study phases (pre-phase and treatment phase) was used to classify patients as satisfied or non-satisfied with the efficacy of their medication. The analysis is based on 1734 patients included in the efficacy analysis of a randomized, placebo-controlled, double-blind, multi-centre parallel group trial with six treatment arms. Based on this classification and the pain intensity recorded by the patients on a 100 mm visual analogue scale, group differences by assessment categories and receiver operating characteristic (ROC) curve methods were used to quantify responsiveness of the efficacy endpoints 'time to 50% pain relief', 'time until reduction of pain intensity to 10 mm', 'weighted sum of pain intensity difference' (%SPIDweighted), 'pain intensity difference (PID) relative to baseline at 2 hours', and 'pain-free at 2 hours'. Clinically relevant differences between patients satisfied and non-satisfied with the treatment were observed for all efficacy endpoints. Patients with the highest rating of efficacy had the fastest and strongest pain relief. In comparison, patients assessing efficacy as 'less good' reached a 50% pain relief on average nearly an hour later than those scoring efficacy as at least 'good'. Simultaneously, their extent of pain relief was only half as great 2 hours after medication intake. Patients scoring efficacy as 'poor' experienced practically no pain relief within the 4 hour observation interval. ROC curve calculations confirmed an adequate responsiveness for all continuous endpoints. The following cut-off points for differentiating between satisfied and non-satisfied patients were deduced from the data in the pre- and treatment phase, respectively: 'time to 50% pain relief' 1:10 and 1:31 h:min, 'time until reduction of pain intensity to 10 mm' 2:40 and 3:00 h:min, '%SPIDweighted' 68 and 64%, 'PID at 2 hours' 35 and 35 mm. The sensitivity and specificity based on these cut-off points ranged from 70 to 79%. The binary endpoint 'pain-free at 2 hours' showed a clearly higher specificity (80 and 87%) than sensitivity (65 and 61%) in the pre- and treatment phase, respectively. When global assessment of efficacy by the patient was used as external criterion, ROC curve calculations confirmed a high responsiveness for all efficacy endpoints included in this study. Clinically relevant differences between patients satisfied and non-satisfied with the treatment were observed. The endpoint '%SPIDweighted' proved slightly but consistently superior to the other endpoints. SPID and %SPIDweighted are not easy to interpret and the time course of pain reduction is of high importance for the patients in the treatment of acute pain, including headache. The endpoint 'pain-free at 2 hours' showed the expected high specificity, but at the cost of a concurrently low sensitivity and clearly makes less use of the available information than the endpoint 'time to 50% pain reduction', which combines the highly relevant aspects of time course and extent of pain reduction. Responsiveness, the ability of an outcome measure to detect clinically important changes in a specific condition of a patient, should be added in future revisions of IHS guidelines for clinical trials in headache disorders.

JSEM: A Framework for Identifying and Evaluating Indicators.

ERIC Educational Resources Information Center

Hyman, Jeffrey B.; Leibowitz, Scott G.

2001-01-01

Presents an approach to identifying and evaluating combinations of indicators when the mathematical relationships between the indicators and an endpoint may not be quantified, a limitation common to many ecological assessments. Uses the framework of Structural Equation Modeling (SEM), which combines path analysis with measurement model, to…

A framework for predicting impacts on ecosystem services from (sub)organismal responses to chemicals

EPA Science Inventory

Protection of ecosystem services is increasingly emphasized as a risk-assessment goal, but there are wide gaps between current ecological risk-assessment endpoints and potential effects on services provided by ecosystems. The authors present a framework that links common ecotoxic...

A Bayesian network approach for causal inferences in pesticide risk assessment and management

EPA Science Inventory

Pesticide risk assessment and management must balance societal benefits and ecosystem protection, based on quantified risks and the strength of the causal linkages between uses of the pesticide and socioeconomic and ecological endpoints of concern. A Bayesian network (BN) is a gr...

Physico-chemical properties of manufactured nanomaterials - Characterisation and relevant methods. An outlook based on the OECD Testing Programme.

PubMed

Rasmussen, Kirsten; Rauscher, Hubert; Mech, Agnieszka; Riego Sintes, Juan; Gilliland, Douglas; González, Mar; Kearns, Peter; Moss, Kenneth; Visser, Maaike; Groenewold, Monique; Bleeker, Eric A J

2018-02-01

Identifying and characterising nanomaterials require additional information on physico-chemical properties and test methods, compared to chemicals in general. Furthermore, regulatory decisions for chemicals are usually based upon certain toxicological properties, and these effects may not be equivalent to those for nanomaterials. However, regulatory agencies lack an authoritative decision framework for nanomaterials that links the relevance of certain physico-chemical endpoints to toxicological effects. This paper investigates various physico-chemical endpoints and available test methods that could be used to produce such a decision framework for nanomaterials. It presents an overview of regulatory relevance and methods used for testing fifteen proposed physico-chemical properties of eleven nanomaterials in the OECD Working Party on Manufactured Nanomaterials' Testing Programme, complemented with methods from literature, and assesses the methods' adequacy and applications limits. Most endpoints are of regulatory relevance, though the specific parameters depend on the nanomaterial and type of assessment. Size (distribution) is the common characteristic of all nanomaterials and is decisive information for classifying a material as a nanomaterial. Shape is an important particle descriptor. The octanol-water partitioning coefficient is undefined for particulate nanomaterials. Methods, including sample preparation, need to be further standardised, and some new methods are needed. The current work of OECD's Test Guidelines Programme regarding physico-chemical properties is highlighted. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

QSAR modeling of cumulative environmental end-points for the prioritization of hazardous chemicals.

PubMed

Gramatica, Paola; Papa, Ester; Sangion, Alessandro

2018-01-24

The hazard of chemicals in the environment is inherently related to the molecular structure and derives simultaneously from various chemical properties/activities/reactivities. Models based on Quantitative Structure Activity Relationships (QSARs) are useful to screen, rank and prioritize chemicals that may have an adverse impact on humans and the environment. This paper reviews a selection of QSAR models (based on theoretical molecular descriptors) developed for cumulative multivariate endpoints, which were derived by mathematical combination of multiple effects and properties. The cumulative end-points provide an integrated holistic point of view to address environmentally relevant properties of chemicals.

Cross-species coherence in effects and modes of action in support of causality determinations in the U.S. Environmental Protection Agency's Integrated Science Assessment for Lead.

PubMed

Lassiter, Meredith Gooding; Owens, Elizabeth Oesterling; Patel, Molini M; Kirrane, Ellen; Madden, Meagan; Richmond-Bryant, Jennifer; Hines, Erin Pias; Davis, J Allen; Vinikoor-Imler, Lisa; Dubois, Jean-Jacques

2015-04-01

The peer-reviewed literature on the health and ecological effects of lead (Pb) indicates common effects and underlying modes of action across multiple organisms for several endpoints. Based on such observations, the United States (U.S.) Environmental Protection Agency (EPA) applied a cross-species approach in the 2013 Integrated Science Assessment (ISA) for Lead for evaluating the causality of relationships between Pb exposure and specific endpoints that are shared by humans, laboratory animals, and ecological receptors (i.e., hematological effects, reproductive and developmental effects, and nervous system effects). Other effects of Pb (i.e., cardiovascular, renal, and inflammatory responses) are less commonly assessed in aquatic and terrestrial wildlife limiting the application of cross-species comparisons. Determinations of causality in ISAs are guided by a framework for classifying the weight of evidence across scientific disciplines and across related effects by considering aspects such as biological plausibility and coherence. As illustrated for effects of Pb where evidence across species exists, the integration of coherent effects and common underlying modes of action can serve as a means to substantiate conclusions regarding the causal nature of the health and ecological effects of environmental toxicants. Published by Elsevier Ireland Ltd.

Ecotoxicity of two organic UV-filters to the freshwater caddisfly Sericostoma vittatum.

PubMed

Campos, Diana; Gravato, Carlos; Fedorova, Ganna; Burkina, Viktoriia; Soares, Amadeu M V M; Pestana, João L T

2017-09-01

Organic ultraviolet filters (UV-filters) used for protection against radiation in personal care products and other materials (e.g. textiles, plastic products) are considered emerging contaminants of aquatic ecosystem. Benzophenone-3 (BP3) and 3-(4-methylbenzylidene)camphor (4-MBC) are the most commonly used organic UV-filters and have been reported in freshwater environments due to contamination through discharges from wastewater treatment plants and swimming pools or by direct contamination from recreational activities. Our aim was to evaluate the ecotoxicological effects of these UV-filters using the freshwater caddisfly Sericostoma vittatum' biochemical biomarkers and energy processing related endpoints (feeding behaviour, energy reserves and cellular metabolism). In laboratory trials, both compounds induced feeding inhibition of S. vittatum at 3.55 mg/kg of BP3 and at concentrations ≥2.57 mg/kg of 4-MBC, decreased carbohydrates content at 3.55 and 6.95 mg/kg of BP3 and 4-MBC respectively, and increased total glutathione levels at concentrations ≥1.45 and 1.35 mg/kg of BP3 and 4-MBC respectively. No significant effects were observed on endpoints associated with oxidative stress, antioxidant defences, phase II biotransformation or neurotoxicity after exposure to the two UV-filters. Our results show that environmental relevant concentrations of BP3 and 4-MBC, can negatively impact freshwater insects and demonstrate the importance of monitoring the ecological effects of organic UV-filters using non-model invertebrate species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Linking stressors and ecological responses

USGS Publications Warehouse

Gentile, J.H.; Solomon, K.R.; Butcher, J.B.; Harrass, M.; Landis, W.G.; Power, M.; Rattner, B.A.; Warren-Hicks, W.J.; Wenger, R.; Foran, Jeffery A.; Ferenc, Susan A.

1999-01-01

To characterize risk, it is necessary to quantify the linkages and interactions between chemical, physical and biological stressors and endpoints in the conceptual framework for ecological risk assessment (ERA). This can present challenges in a multiple stressor analysis, and it will not always be possible to develop a quantitative stressor-response profile. This review commences with a conceptual representation of the problem of developing a linkage analysis for multiple stressors and responses. The remainder of the review surveys a variety of mathematical and statistical methods (e.g., ranking methods, matrix models, multivariate dose-response for mixtures, indices, visualization, simulation modeling and decision-oriented methods) for accomplishing the linkage analysis for multiple stressors. Describing the relationships between multiple stressors and ecological effects are critical components of 'effects assessment' in the ecological risk assessment framework.

Linking adverse outcome pathways and population models: Current state of the science and future directions

EPA Science Inventory

Analysis of population impacts of chemical stressors through the use of modeling provides a linkage between endpoints observed in the individual and ecological risk to the population as a whole. In this presentation, we describe the evolution of an approach developed in our labor...

Ecological Threshold for Toxicological Concern (eco-TTC): exploring the importance of non-standard species

EPA Science Inventory

The Threshold for Toxicological Concern (TTC) is well-established for assessing human safety of indirect food-contact substances and has been applied to a variety of endpoints. Recently, we have proposed an extension to the human safety TTC concept for environmental applications,...

FACTORS AFFECTING REPRODUCTION AND THE IMPORTANCE OF ADULT SIZE ON REPRODUCTIVE OUTPUT OF THE MIDGE, CHIRONOMUS TENTANS

EPA Science Inventory

Incorporating reproductive endpoints into sediment toxicity tests has become an important consideration in ecological risk assessments. The capacity to assess reproduction was one of the primary objectives underlying the recent development of a life-cycle test with the midge, Ch...

EUTROPHICATION MODELING CAPABILITIES FOR WATER QUALITY AND INTEGRATION TOWARDS ECOLOGICAL ENDPOINTS

EPA Science Inventory

A primary environmental focus for the use of mathematical models is for characterization of sources of nutrients and sediments and their relative loadings from large river basins, and the impact of land uses from smaller sub-basins on water quality in rivers, lakes, and estuaries...

DEVELOPMENT OF QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS TO PREDICT TOXICITY FOR A VARIETY OF HUMAN AND ECOLOGICAL ENDPOINTS

EPA Science Inventory

The number of chemicals released into the environment has significantly increased over the past few years, leading to increased risk of human exposure through inhalation, ingestion, or dermal uptake. In addition, the risk also increases with increasing toxicity of the chemical. ...

Connecting Ecosystem Service Production to Users as a Measure of Realized Benefits in Coastal Communities

EPA Science Inventory

Ecosystem goods and services are often produced in locations far away from where humans benefit from them. Human beneficiaries also use specific spatial pathways to access the Final Ecosystem Goods and Services (FEGS), the ecological endpoints directly beneficial to human well-b...

Phytotoxicity of silver nanoparticles to Lemna minor: Surface coating and exposure period-related effects.

PubMed

Pereira, Susana P P; Jesus, Fátima; Aguiar, Sara; de Oliveira, Rhaul; Fernandes, Marco; Ranville, James; Nogueira, António J A

2018-03-15

Silver nanoparticles (Ag NPs) exponential production raises concern about their environmental impact. The effects of Ag NPs to aquatic plants remain scarcely studied, especially in extended exposures. This paper aims to evaluate Ag NPs effects in Lemna minor at individual and sub-individual levels, focusing on three variables: Ag form (NPs versus ions - Ag + ), NPs surface coating (citrate vs polyvinylpyrrolidone - PVP) and exposure period (7 vs 14days). Endpoints were assessed at individual level (specific growth rate, chlorosis incidence and number of fronds per colony) and sub-individual level (enzymatic activities of catalase (CAT), guaiacol peroxidase (GPx) and glutathione-S-transferase (GST)). Generally, plants exposed to all Ag forms underwent decays on growth rate and fronds per colony, and increases on chlorosis, GPX and GST, but no effects on CAT. The most sensitive endpoints were specific growth rate and GPx activity, showing significant effects down to 0.05mg/L for Ag NPs and 3μg/L for Ag + , after 14days. Ag + showed higher toxicity with a 14d-EC 50 of 0.0037mg Ag/L. Concerning surface coating, PVP-Ag NPs were more deleterious on growth rate and fronds per colony, whereas citrate-Ag NPs affected more the chlorosis incidence and GPx and GST activities. The exposure period significantly affected chlorosis: 14days triggered a chlorosis increase in Ag + -exposed plants and a decrease in Ag NPs-exposed plants when compared to 7days. Ag NPs induced an oxidative stress status in cells, thus ensuing upregulated enzymatic activity as a self-defense mechanism. Since Ag NPs dissolution might occur on a steady and continuous mode along time, and the average longevity of fronds, we propose longer exposures periods than the recommended by the OECD guideline. This approach would provide more relevant and holistic evidences on the overall response of freshwater plants to Ag NPs in an ecological relevant scenario. Copyright © 2017 Elsevier B.V. All rights reserved.

Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process.

PubMed

Ponsioen, Cyriel Y; Chapman, Roger W; Chazouillères, Olivier; Hirschfield, Gideon M; Karlsen, Tom H; Lohse, Ansgar W; Pinzani, Massimo; Schrumpf, Erik; Trauner, Michael; Gores, Gregory J

2016-04-01

Primary sclerosing cholangitis (PSC) is a rare, but serious, cholestatic disease for which, to date, no effective therapy exists to halt disease progression toward end-stage liver disease. Clinical trial design to study drugs that improve prognosis is hampered by the relatively low event rate of clinically relevant endpoints. To overcome this shortcoming, there is an urgent need to identify appropriate surrogate endpoints. At present, there are no established surrogate endpoints. This article provides a critical review and describes the results of a consensus process initiated by the International PSC Study Group to delineate appropriate candidate surrogate endpoints at present for clinical trials in this frequently dismal disease. The consensus process resulted in a shortlist of five candidates as surrogate endpoints for measuring disease progression: alkaline phosphatase (ALP); transient elastography (TE); histology; combination of ALP+histology; and bilirubin. Of these, histology, ALP, and TE came out as the most promising. However, the expert panel concluded that no biomarker currently exceeds level 3 validation. Combining multiple endpoints is advisable. At present, there are insufficient data to support level 2 validation for any surrogate endpoint in PSC. Concerted efforts by all stakeholders are highly needed. Novel, promising noninvasive biomarkers are under study and should be incorporated as exploratory endpoints in clinical trials. © 2015 by the American Association for the Study of Liver Diseases.

Statistical evaluation of the Local Lymph Node Assay.

PubMed

Hothorn, Ludwig A; Vohr, Hans-Werner

2010-04-01

In the Local Lymph Node Assay measured endpoints for each animal, such as cell proliferation, cell counts and/or lymph node weight should be evaluated separately. The primary criterion for a positive response is when the estimated stimulation index is larger than a specified relative threshold that is endpoint- and strain-specific. When the lower confidence limit for ratio-to-control comparisons is larger than a relevance threshold, a biologically relevant increase can be concluded according to the proof of hazard. Alternatively, when the upper confidence limit for ratio-to-control comparisons is smaller than a tolerable margin, harmlessness can be concluded according to a proof of safety. Copyright 2009 Elsevier Inc. All rights reserved.

Developing predictive systems models to address complexity and relevance for ecological risk assessment.

PubMed

Forbes, Valery E; Calow, Peter

2013-07-01

Ecological risk assessments (ERAs) are not used as well as they could be in risk management. Part of the problem is that they often lack ecological relevance; that is, they fail to grasp necessary ecological complexities. Adding realism and complexity can be difficult and costly. We argue that predictive systems models (PSMs) can provide a way of capturing complexity and ecological relevance cost-effectively. However, addressing complexity and ecological relevance is only part of the problem. Ecological risk assessments often fail to meet the needs of risk managers by not providing assessments that relate to protection goals and by expressing risk in ratios that cannot be weighed against the costs of interventions. Once more, PSMs can be designed to provide outputs in terms of value-relevant effects that are modulated against exposure and that can provide a better basis for decision making than arbitrary ratios or threshold values. Recent developments in the modeling and its potential for implementation by risk assessors and risk managers are beginning to demonstrate how PSMs can be practically applied in risk assessment and the advantages that doing so could have. Copyright © 2013 SETAC.

Insights into the CuO nanoparticle ecotoxicity with suitable marine model species.

PubMed

Rotini, A; Gallo, A; Parlapiano, I; Berducci, M T; Boni, R; Tosti, E; Prato, E; Maggi, C; Cicero, A M; Migliore, L; Manfra, L

2018-01-01

Metal oxide nanoparticles, among them copper oxide nanoparticles (CuO NPs), are widely used in different applications (e.g. batteries, gas sensors, superconductors, plastics and metallic coatings), increasing their potential release in the environment. In aquatic matrix, the behavior of CuO NPs may strongly change, depending on their surface charge and some physical-chemical characteristics of the medium (e.g. ionic strength, salinity, pH and natural organic matter content). Ecotoxicity of CuO NPs to aquatic organisms was mainly studied on freshwater species, few tests being performed on marine biota. The aim of this study was to assess the toxicity of CuO NPs on suitable indicator species, belonging to the ecologically relevant level of consumers. The selected bioassays use reference protocols to identify Effect/Lethal Concentrations (E(L)C), by assessing lethal and sub-lethal endpoints. Mortality tests were performed on rotifer (Brachionus plicatilis), shrimp (Artemia franciscana) and copepod (Tigriopus fulvus). While moult release failure and fertilization rate were studied, as sub-lethal endpoints, on T. fulvus and sea urchin (Paracentrotus lividus), respectively. The size distribution and sedimentation rates of CuO NPs, together with the copper dissolution, were also analyzed in the exposure media. The CuO NP ecotoxicity assessment showed a concentration-dependent response for all species, indicating similar mortality for B. plicatilis (48hLC 50 = 16.94 ± 2.68mg/l) and T. fulvus (96hLC 50 = 12.35 ± 0.48mg/l), followed by A. franciscana (48hLC 50 = 64.55 ± 3.54mg/l). Comparable EC 50 values were also obtained for the sub-lethal endpoints in P. lividus (EC 50 = 2.28 ± 0.06mg/l) and T. fulvus (EC 50 = 2.38 ± 0.20mg/l). Copper salts showed higher toxicity than CuO NPs for all species, with common sensitivity trend as follows: P. lividus ≥ T. fulvus (sublethal endpoint) ≥ B. plicatilis >T. fulvus (lethal endpoint) >A. franciscana. CuO NP micrometric aggregates and high sedimentation rates were observed in the exposure media, with different particle size distributions depending on the medium. The copper dissolution was about 0.16% of the initial concentration, comparable to literature values. The integrated ecotoxicological-physicochemical approach was used to better describe CuO NP toxicity and behavior. In particular, the successful application of ecotoxicological reference protocols allowed to produce reliable L(E)C data useful to identify thresholds and assess potential environmental hazard due to NPs. Copyright © 2017 Elsevier Inc. All rights reserved.

Designing a Quantitative Structure-Activity Relationship for the Intrinsic Metabolic Clearance of Environmentally Relevant Chemicals

EPA Science Inventory

Toxicokinetic models serve a vital role in risk assessment by bridging the gap between chemical exposure and potentially toxic endpoints. While intrinsic metabolic clearance rates have a strong impact on toxicokinetics, limited data is available for environmentally relevant chemi...

Methods Development for a Spatially Explicit Population-Level Risk Assessment, Uncertainty Analysis, and Comparison with Risk Quotient Approaches

EPA Science Inventory

The standard framework of Ecological Risk Assessment (ERA) uses organism-level assessment endpoints to qualitatively determine the risk to populations. While organism-level toxicity data provide the pathway by which a species may be affected by a chemical stressor, they neither i...

EVALUATING THE ECOLOGICAL SIGNIFICANCE OF LABORATORY RESPONSE DATA TO PREDICT POPULATION-LEVEL EFFECTS FOR THE ESTUARINE AMPHIPOD, AMPILISCA ABDITA

EPA Science Inventory

Ten-day acute mortality of the benthic amphipod Ampelisca abdita is used in a number of regulatory, research, and monitoring programs to evaluate chemical contamination of marine sediments. Although this endpoint has proven to be valuable for characterizing the relative toxicitie...

DEVELOPMENT OF QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS (QSARS) TO PREDICT TOXICITY FOR A VARIETY OF HUMAN AND ECOLOGICAL ENDPOINTS

EPA Science Inventory

In general, the accuracy of a predicted toxicity value increases with increase in similarity between the query chemical and the chemicals used to develop a QSAR model. A toxicity estimation methodology employing this finding has been developed. A hierarchical based clustering t...

Tracking genes of ecological relevance using a genome scan in two independent regional population samples of Arabis alpina.

PubMed

Poncet, Bénédicte N; Herrmann, Doris; Gugerli, Felix; Taberlet, Pierre; Holderegger, Rolf; Gielly, Ludovic; Rioux, Delphine; Thuiller, Wilfried; Aubert, Serge; Manel, Stéphanie

2010-07-01

Understanding the genetic basis of adaptation in response to environmental variation is fundamental as adaptation plays a key role in the extension of ecological niches to marginal habitats and in ecological speciation. Based on the assumption that some genomic markers are correlated to environmental variables, we aimed to detect loci of ecological relevance in the alpine plant Arabis alpina L. sampled in two regions, the French (99 locations) and the Swiss (109 locations) Alps. We used an unusually large genome scan [825 amplified fragment length polymorphism loci (AFLPs)] and four environmental variables related to temperature, precipitation and topography. We detected linkage disequilibrium among only 3.5% of the considered AFLP loci. A population structure analysis identified no admixture in the study regions, and the French and Swiss Alps were differentiated and therefore could be considered as two independent regions. We applied generalized estimating equations (GEE) to detect ecologically relevant loci separately in the French and Swiss Alps. We identified 78 loci of ecological relevance (9%), which were mainly related to mean annual minimum temperature. Only four of these loci were common across the French and Swiss Alps. Finally, we discuss that the genomic characterization of these ecologically relevant loci, as identified in this study, opens up new perspectives for studying functional ecology in A. alpina, its relatives and other alpine plant species.

Terrestrial population models for ecological risk assessment: A state-of-the-art review

USGS Publications Warehouse

Emlen, J.M.

1989-01-01

Few attempts have been made to formulate models for predicting impacts of xenobiotic chemicals on wildlife populations. However, considerable effort has been invested in wildlife optimal exploitation models. Because death from intoxication has a similar effect on population dynamics as death by harvesting, these management models are applicable to ecological risk assessment. An underlying Leslie-matrix bookkeeping formulation is widely applicable to vertebrate wildlife populations. Unfortunately, however, the various submodels that track birth, death, and dispersal rates as functions of the physical, chemical, and biotic environment are by their nature almost inevitably highly species- and locale-specific. Short-term prediction of one-time chemical applications requires only information on mortality before and after contamination. In such cases a simple matrix formulation may be adequate for risk assessment. But generally, risk must be projected over periods of a generation or more. This precludes generic protocols for risk assessment and also the ready and inexpensive predictions of a chemical's influence on a given population. When designing and applying models for ecological risk assessment at the population level, the endpoints (output) of concern must be carefully and rigorously defined. The most easily accessible and appropriate endpoints are (1) pseudoextinction (the frequency or probability of a population falling below a prespecified density), and (2) temporal mean population density. Spatial and temporal extent of predicted changes must be clearly specified a priori to avoid apparent contradictions and confusion.

Determining the Primary Endpoint for a Stimulant Abuse Trial: Lessons Learned from STRIDE (CTN 0037)

PubMed Central

Trivedi, Madhukar H.; Greer, Tracy L.; Potter, Jennifer Sharpe; Grannemann, Bruce D.; Nunes, Edward V.; Rethorst, Chad; Warden, Diane; Ring, Kolette M.; Somoza, Eugene

2012-01-01

Background No consensus is available for identifying the best primary outcome for substance abuse trials. While abstinence is the most desirable outcome for substance use interventions, a wide variety of other endpoints have been used to evaluate efficacy trials. Objectives This report provides a framework for determining an optimal primary endpoint and the relevant measurement approach for substance use disorder treatment trials. The framework was developed based on a trial for stimulant abuse using exercise as an augmentation treatment, delivered within the NIDA Clinical Trials Network. The use of a common primary endpoint across trials will facilitate comparisons of treatment efficacy. Methods Primary endpoint options in existing substance abuse studies were evaluated. This evaluation included surveys of the literature for endpoints and measurement approaches, followed by assessment of endpoint choices against study design issues, population characteristics, tests of sensitivity and tests of clinical meaningfulness. Conclusion We concluded that the best current choice for a primary endpoint is percent days abstinent, as measured by the Time Line Follow Back (TLFB) interview conducted three times a week with recall aided by a take-home Substance Use Diary. To further improve the accuracy of the self-reported drug use, an algorithm will be applied to reconcile the results from the TLFB with the results of qualitative urine drug screens. Scientific Significance There is a need for a standardized endpoint in this field to allow for comparison across treatment studies, and we suggest that the recommended endpoint be considered for use in this field. PMID:21854276

Transmission models and management of lymphatic filariasis elimination.

PubMed

Michael, Edwin; Gambhir, Manoj

2010-01-01

The planning and evaluation of parasitic control programmes are complicated by the many interacting population dynamic and programmatic factors that determine infection trends under different control options. A key need is quantification about the status of the parasite system state at any one given timepoint and the dynamic change brought upon that state as an intervention program proceeds. Here, we focus on the control and elimination of the vector-borne disease, lymphatic filariasis, to show how mathematical models of parasite transmission can provide a quantitative framework for aiding the design of parasite elimination and monitoring programs by their ability to support (1) conducting rational analysis and definition of endpoints for different programmatic aims or objectives, including transmission endpoints for disease elimination, (2) undertaking strategic analysis to aid the optimal design of intervention programs to meet set endpoints under different endemic settings and (3) providing support for performing informed evaluations of ongoing programs, including aiding the formation of timely adaptive management strategies to correct for any observed deficiencies in program effectiveness. The results also highlight how the use of a model-based framework will be critical to addressing the impacts of ecological complexities, heterogeneities and uncertainties on effective parasite management and thereby guiding the development of strategies to resolve and overcome such real-world complexities. In particular, we underscore how this approach can provide a link between ecological science and policy by revealing novel tools and measures to appraise and enhance the biological controllability or eradicability of parasitic diseases. We conclude by emphasizing an urgent need to develop and apply flexible adaptive management frameworks informed by mathematical models that are based on learning and reducing uncertainty using monitoring data, apply phased or sequential decision-making to address extant uncertainty and focus on developing ecologically resilient management strategies, in ongoing efforts to control or eliminate filariasis and other parasitic diseases in resource-poor communities.

Determination of the Biologically Relevant Sampling Depth for Terrestrial and Aquatic Ecological Risk Assessments (Final Report)

EPA Science Inventory

The Ecological Risk Assessment Support Center (ERASC) announced the release of the final report, Determination of the Biologically Relevant Sampling Depth for Terrestrial and Aquatic Ecological Risk Assessments. This technical paper provides defensible approximations fo...

A "weight of evidence" approach for the integration of environmental "triad" data to assess ecological risk and biological vulnerability.

PubMed

Dagnino, Alessandro; Sforzini, Susanna; Dondero, Francesco; Fenoglio, Stefano; Bona, Elisa; Jensen, John; Viarengo, Aldo

2008-07-01

A new Expert Decision Support System (EDSS) that can integrate Triad data for assessing environmental risk and biological vulnerability at contaminated sites has been developed. Starting with ecosystem relevance, the EDSS assigns different weights to the results obtained from Triad disciplines. The following parameters have been employed: 1) chemical soil analyses (revealing the presence of potentially dangerous substances), 2) ecotoxicological bioassays (utilizing classical endpoints such as survival and reproduction rates), 3) biomarkers (showing sublethal pollutant effects), and 4) ecological parameters (assessing changes in community structure and functions). For each Triad discipline, the EDSS compares the data obtained at the studied field sites with reference values and calculates different 0-1 indexes (e.g., Chemical Risk Index, Ecotoxicological Risk Index, and Ecological Risk Index). The EDSS output consists of 3 indexes: 1) Environmental Risk index (EnvRI), quantifying the levels of biological damage at population-community level, 2) Biological Vulnerability Index (BVI), assessing the potential threats to biological equilibriums, and 3) Genotoxicity Index (GTI), screening genotoxicity effects. The EDSS has been applied in the integration of a battery of Triad data obtained during the European Union-funded Life Intervention in the Fraschetta Area (LINFA) project, which has been carried out in order to estimate the potential risk from soils of a highly anthropized area (Alessandria, Italy) mainly impacted by deposition of atmospheric pollutants. Results obtained during 4 seasonal sampling campaigns (2004-2005) show maximum values of EnvRI in sites A and B (characterized by industrial releases) and lower levels in site D (affected by vehicular traffic emissions). All 3 potentially polluted sites have shown high levels of BVI and GTI, suggesting a general change from reference conditions (site C).

Getting More Ecologically Relevant Information from Laboratory Tests: Recovery of Lemna minor After Exposure to Herbicides and Their Mixtures.

PubMed

Knežević, Varja; Tunić, Tanja; Gajić, Pero; Marjan, Patricija; Savić, Danko; Tenji, Dina; Teodorović, Ivana

2016-11-01

Recovery after exposure to herbicides-atrazine, isoproturon, and trifluralin-their binary and ternary mixtures, was studied under laboratory conditions using a slightly adapted standard protocol for Lemna minor. The objectives of the present study were (1) to compare empirical to predicted toxicity of selected herbicide mixtures; (2) to assess L. minor recovery potential after exposure to selected individual herbicides and their mixtures; and (3) to suggest an appropriate recovery potential assessment approach and endpoint in a modified laboratory growth inhibition test. The deviation of empirical from predicted toxicity was highest in binary mixtures of dissimilarly acting herbicides. The concentration addition model slightly underestimated mixture effects, indicating potential synergistic interactions between photosynthetic inhibitors (atrazine and isoproturon) and a cell mitosis inhibitor (trifluralin). Recovery after exposure to the binary mixture of atrazine and isoproturon was fast and concentration-independent: no significant differences between relative growth rates (RGRs) in any of the mixtures (IC10 Mix , 25 Mix , and 50 Mix ) versus control level were recorded in the last interval of the recovery phase. The recovery of the plants exposed to binary and ternary mixtures of dissimilarly acting herbicides was strictly concentration-dependent. Only plants exposed to IC10 Mix , regardless of the herbicides, recovered RGRs close to control level in the last interval of the recovery phase. The inhibition of the RGRs in the last interval of the recovery phase compared with the control level is a proposed endpoint that could inform on reversibility of the effects and indicate possible mixture effects on plant population recovery potential.

Application of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks to advance cumulative risk assessment by integrating human health and ecological endpoints

EPA Science Inventory

Evaluating risk of adverse outcomes from chemical exposure is essential for understanding the impacts of environmental contaminants. While human health outcomes are of primary concern and are often the focus of risk assessments, important non-human species are also exposed to co...

Application of Biochemical Markers for Population Level Assessment of a White Sucker (Catostomus commersoni) Population Exposed to Bleached Kraft Pulp Mill Effluent

EPA Science Inventory

A need in ecological risk assessment is an approach that can be used to link chemically-induced alterations in molecular and biochemical endpoints to adverse outcomes in whole organisms and populations. A predictive population model was developed to translate changes in fecundit...

CAN A MODEL TRANSFERABILITY FRAMEWORK IMPROVE ECOSYSTEM SERVICE ESTIMATES? A CASE STUDY OF SOIL FOREST CARBON SEQUESTRATION IN TILLAMOOK BAY, OR, USA

EPA Science Inventory

Budget constraints and policies that limit primary data collection have fueled a practice of transferring estimates (or models to generate estimates) of ecological endpoints from sites where primary data exists to sites where little to no primary data were collected. Whereas bene...

Old model organisms and new behavioral end-points: Swimming alteration as an ecotoxicological response.

PubMed

Faimali, Marco; Gambardella, Chiara; Costa, Elisa; Piazza, Veronica; Morgana, Silvia; Estévez-Calvar, Noelia; Garaventa, Francesca

2017-07-01

Behavioral responses of aquatic organisms have received much less attention than developmental or reproductive ones due to the scarce presence of user-friendly tools for their acquisition. The technological development of data acquisition systems for quantifying behavior in the aquatic environment and the increase of studies on the understanding the relationship between the behavior of aquatic organisms and the physiological/ecological activities have generated renewed interest in using behavioral responses also in marine ecotoxicology. Recent reviews on freshwater environment show that behavioral end-points are comparatively fast and sensitive, and warrant further attention as tools for assessing the toxicological effects of environmental contaminants. In this mini-review, we perform a systematic analysis of the most recent works that have used marine invertebrate swimming alteration as behavioral end-point in ecotoxicological studies by assessing the differences between behavioral and acute responses in a wide range of species, in order to compare their sensitivity. Copyright © 2016. Published by Elsevier Ltd.

Toxicity data for modeling impacts of oil components in an Arctic ecosystem.

PubMed

Olsen, G H; Klok, C; Hendriks, A J; Geraudie, P; De Hoop, L; De Laender, F; Farmen, E; Grøsvik, B E; Hansen, B H; Hjorth, M; Jansen, C R; Nordtug, T; Ravagnan, E; Viaene, K; Carroll, J

2013-09-01

Ecological impact assessment modeling systems are valuable support tools for managing impacts from commercial activities on marine habitats and species. The inclusion of toxic effects modeling in these systems is predicated on the availability and quality of ecotoxicology data. Here we report on a data gathering exercise to obtain toxic effects data on oil compounds for a selection of cold-water marine species of fish and plankton associated with the Barents Sea ecosystem. Effects data were collated from historical and contemporary literature resources for the endpoints mortality, development, growth, bioaccumulation and reproduction. Evaluating the utility and applicability of these data for modeling, we find that data coverage is limited to a sub-set of the required endpoints. There is a need for new experimental studies for zooplankton focused on the endpoints development and bioaccumulation and for larvae and juvenile fish focused on growth and development. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Reliability of a Manual Procedure for Marking the EZ Endpoint Location in Patients with Retinitis Pigmentosa

PubMed Central

Ramachandran, Rithambara; Cai, Cindy X.; Lee, Dongwon; Epstein, Benjamin C.; Locke, Kirsten G.; Birch, David G.; Hood, Donald C.

2016-01-01

Purpose We developed and evaluated a training procedure for marking the endpoints of the ellipsoid zone (EZ), also known as the inner segment/outer segment (IS/OS) border, on frequency domain optical coherence tomography (fdOCT) scans from patients with retinitis pigmentosa (RP). Methods A manual for marking EZ endpoints was developed and used to train 2 inexperienced graders. After training, an experienced grader and the 2 trained graders marked the endpoints on fdOCT horizontal line scans through the macula from 45 patients with RP. They marked the endpoints on these same scans again 1 month later. Results Intragrader agreement was excellent. The intraclass correlation coefficient (ICC) was 0.99, the average difference of endpoint locations (19.6 μm) was close to 0 μm, and the 95% limits were between −284 and 323 μm, approximately ±1.1°. Intergrader agreement also was excellent. The ICC values were 0.98 (time 1) and 0.97 (time 2), the average difference among graders was close to zero, and the 95% limits of these differences was less than 350 μm, approximately 1.2°, for both test times. Conclusions While automated algorithms are becoming increasingly accurate, EZ endpoints still have to be verified manually and corrected when necessary. With training, the inter- and intragrader agreement of manually marked endpoints is excellent. Translational Relevance For clinical studies, the EZ endpoints can be marked by hand if a training procedure, including a manual, is used. The endpoint confidence intervals, well under ±2.0°, are considerably smaller than the 6° spacing for the typically used static visual field. PMID:27226930

Confirmatory versus explorative endpoint analysis: Decision-making on the basis of evidence available from market authorization and early benefit assessment for oncology drugs.

PubMed

Niehaus, Ines; Dintsios, Charalabos-Markos

2018-06-01

The early benefit assessment of pharmaceuticals in Germany and their preceding market authorization pursue different objectives. This is reflected by the inclusion of varying confirmatory endpoints within the evaluation of oncology drugs in early benefit assessment versus market authorization, with both relying on the same evidence. Data from assessments up to July 2015 are used to estimate the impact of explorative in comparison to confirmatory endpoints on market authorization and early benefit assessment by contrasting the benefit-risk ratio of EMA and the benefit-harm balance of the HTA jurisdiction. Agreement between market authorization and early benefit assessment is examined by Cohen's kappa (k). 21 of 41 assessments were considered in the analysis. Market authorization is more confirmatory than early benefit assessment because it includes a higher proportion of primary endpoints. The latter implies a primary endpoint to be relevant for the benefit-harm balance in only 67% of cases (0.078). Explorative mortality endpoints reached the highest agreement regarding the mutual consideration for the risk-benefit ratio and the benefit-harm balance (0.000). For explorative morbidity endpoints (-0.600), quality of life (-0.600) and side effects (-0.949) no agreement is ascertainable. To warrant a broader confirmatory basis for decisions supported by HTA, closer inter-institutional cooperation of approval authorities and HTA jurisdictions by means of reliable joint advice for manufacturers regarding endpoint definition would be favorable. Copyright © 2018 Elsevier B.V. All rights reserved.

Classification and Dose-Response Characterization of ...

EPA Pesticide Factsheets

Thirty years and over a billion of today’s dollars worth of pesticide registration toxicity studies, historically stored as hardcopy and scanned documents, have been digitized into highly standardized and structured toxicity data, within the U.S. Environmental Protection Agency’s (EPA) Toxicity Reference Database (ToxRefDB). The source toxicity data in ToxRefDB covers multiple study types, including subchronic, developmental, reproductive, chronic, and cancer studies, resulting in a diverse set of endpoints and toxicities. Novel approaches to chemical classification are performed as a model application of ToxRefDB and as an essential need for highly detailed chemical classifications within the EPA’s ToxCast™ research program. In order to develop predictive models and biological signatures utilizing high-throughput screening (HTS) and in vitro genomic data, endpoints and toxicities must first be identified and globally characterized for ToxCast Phase I chemicals. Secondarily, dose-response characterization within and across toxicity endpoints provide insight into key precursor toxicity events and overall endpoint relevance. Toxicity-based chemical classification and dose-response characterization utilizing ToxRefDB prioritized toxicity endpoints and differentiated toxicity outcomes across a large chemical set.

Weighted analysis of composite endpoints with simultaneous inference for flexible weight constraints.

PubMed

Duc, Anh Nguyen; Wolbers, Marcel

2017-02-10

Composite endpoints are widely used as primary endpoints of randomized controlled trials across clinical disciplines. A common critique of the conventional analysis of composite endpoints is that all disease events are weighted equally, whereas their clinical relevance may differ substantially. We address this by introducing a framework for the weighted analysis of composite endpoints and interpretable test statistics, which are applicable to both binary and time-to-event data. To cope with the difficulty of selecting an exact set of weights, we propose a method for constructing simultaneous confidence intervals and tests that asymptotically preserve the family-wise type I error in the strong sense across families of weights satisfying flexible inequality or order constraints based on the theory of χ¯2-distributions. We show that the method achieves the nominal simultaneous coverage rate with substantial efficiency gains over Scheffé's procedure in a simulation study and apply it to trials in cardiovascular disease and enteric fever. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Discovering ecologically relevant knowledge from published studies through geosemantic searching

USDA-ARS?s Scientific Manuscript database

It is easier to search the globe for research on genes of a local plant or animal than to find local field research on that plant’s ecology. While internet applications can find the closest coffee shop, it is difficult to find where the nearest relevant research was conducted. As a result, ecologi...

Meta-analysis of thirty-two case-control and two ecological radon studies of lung cancer.

PubMed

Dobrzynski, Ludwik; Fornalski, Krzysztof W; Reszczynska, Joanna

2018-03-01

A re-analysis has been carried out of thirty-two case-control and two ecological studies concerning the influence of radon, a radioactive gas, on the risk of lung cancer. Three mathematically simplest dose-response relationships (models) were tested: constant (zero health effect), linear, and parabolic (linear-quadratic). Health effect end-points reported in the analysed studies are odds ratios or relative risk ratios, related either to morbidity or mortality. In our preliminary analysis, we show that the results of dose-response fitting are qualitatively (within uncertainties, given as error bars) the same, whichever of these health effect end-points are applied. Therefore, we deemed it reasonable to aggregate all response data into the so-called Relative Health Factor and jointly analysed such mixed data, to obtain better statistical power. In the second part of our analysis, robust Bayesian and classical methods of analysis were applied to this combined dataset. In this part of our analysis, we selected different subranges of radon concentrations. In view of substantial differences between the methodology used by the authors of case-control and ecological studies, the mathematical relationships (models) were applied mainly to the thirty-two case-control studies. The degree to which the two ecological studies, analysed separately, affect the overall results when combined with the thirty-two case-control studies, has also been evaluated. In all, as a result of our meta-analysis of the combined cohort, we conclude that the analysed data concerning radon concentrations below ~1000 Bq/m3 (~20 mSv/year of effective dose to the whole body) do not support the thesis that radon may be a cause of any statistically significant increase in lung cancer incidence.

Toxicity assessment of diesel- and metal-contaminated soils through elutriate and solid phase assays with the slime mold Dictyostelium discoideum.

PubMed

Rodríguez-Ruiz, Amaia; Dondero, Francesco; Viarengo, Aldo; Marigómez, Ionan

2016-06-01

A suite of organisms from different taxonomical and ecological positions is needed to assess environmentally relevant soil toxicity. A new bioassay based on Dictyostelium is presented that is aimed at integrating slime molds into such a testing framework. Toxicity tests on elutriates and the solid phase developmental cycle assay were successfully applied to a soil spiked with a mixture of Zn, Cd, and diesel fuel freshly prepared (recently contaminated) and after 2 yr of aging. The elutriates of both soils provoked toxic effects, but toxicity was markedly lower in the aged soil. In the D. discoideum developmental cycle assay, both soils affected amoeba viability and aggregation, with fewer multicellular units, smaller fruiting bodies and, overall, inhibition of fruiting body formation. This assay is quick and requires small amounts of test soil, which might facilitate its incorporation into a multispecies multiple-endpoint toxicity bioassay battery suitable for environmental risk assessment in soils. Environ Toxicol Chem 2016;35:1413-1421. © 2015 SETAC. © 2015 SETAC.

Acute toxicity of polybrominated diphenyl ethers (PBDEs) for turbot (Psetta maxima) early life stages (ELS).

PubMed

Mhadhbi, Lazhar; Fumega, José; Boumaiza, Moncef; Beiras, Ricardo

2012-03-01

The environmental presence of polybrominated diphenyl ethers (PBDEs), among which BDE-47 and BDE-99 are particularly abundant, makes toxicity data necessary to assess the hazard risk posed by PBDE to aquatic organisms. This study examines the effects of BDE-47 and BDE-99 on embryo-larval stages of the marine flatfish turbot. The turbot embryos were exposed at nominal concentrations of BDE-47 and BDE-99 for 6 days. Selected dose levels were relevant for investigating sublethal and lethal effects. Both tested compounds caused lethal toxicity as well as non-lethal malformations during embryo development. We found a high toxic potency of BDE-47 compared to BDE-99 (LC₅₀ values for embryos and larvae, respectively, BDE-47: 27.35 and 14.13 μg L⁻¹; BDE-99: 38.28 and 29.64 μg L⁻¹). The present study shows high sensitivity of fish early life stages (ELS) to PBDE compounds. Based on environmental concentrations of dissolved PBDEs from various aquatic ecosystems, waterborne BDE-47 and BDE-99 pose little risk of acute toxicity to marine fish at relevant environmental concentrations. Turbot fish ELS proved to be an excellent model for the study of ecotoxicity of contaminants in seawater. The results demonstrate harmful effects of PBDE on turbot ELS at concentrations in the range of parts per billion units. In the perspective of risk assessment, ELS endpoints provide rapid, cost-effective and ecologically relevant information, and links should be sought between these short-term tests and effects of long-term exposures in more realistic scenarios.

Cross-Species Coherence in Effects and Modes of Action in Support of Causality Determinations in the U.S. Environmental Protection Agency’s Integrated Science Assessment for Lead

EPA Science Inventory

The peer-reviewed literature on the health and ecological effects of lead (Pb) indicates common effects and underlying modes of action across multiple organisms for several endpoints. Based on such observations, the United States Environmental Protection Agency (EPA) applied a cr...

The Role of Biomarkers in the Assessment of Aquatic Ecosystem Health

PubMed Central

Hook, Sharon E; Gallagher, Evan P; Batley, Graeme E

2016-01-01

Ensuring the health of aquatic ecosystems and identifying species at risk from the detrimental effects of environmental contaminants can be facilitated by integrating analytical chemical analysis with carefully selected biological endpoints measured in tissues of species of concern. These biological endpoints include molecular, biochemical and physiological markers (i.e. biomarkers) that when integrated, can clarify issues of contaminant bioavailability, bioaccumulation and ecological effects while enabling a better understanding of the effects of non-chemical stressors. In the case of contaminant stressors, an understanding of chemical modes of toxicity can be incorporated with diagnostic markers of aquatic animal physiology to help understand the health status of aquatic organisms in the field. Furthermore, new approaches in functional genomics and bioinformatics can help discriminate individual chemicals, or groups of chemicals among complex mixtures that may contribute to adverse biological effects. While the use of biomarkers is not a new paradigm, such approaches have been underutilized in the context of ecological risk assessment and natural resource damage assessment. From a regulatory standpoint, these approaches can help better assess the complex effects from coastal development activities to assessing ecosystem integrity pre- and post-development or site remediation. PMID:24574147

Multisite Comparison of Anti-Human Immunodeficiency Virus Microbicide Activity in Explant Assays Using a Novel Endpoint Analysis ▿ †

PubMed Central

Richardson-Harman, Nicola; Lackman-Smith, Carol; Fletcher, Patricia S.; Anton, Peter A.; Bremer, James W.; Dezzutti, Charlene S.; Elliott, Julie; Grivel, Jean-Charles; Guenthner, Patricia; Gupta, Phalguni; Jones, Maureen; Lurain, Nell S.; Margolis, Leonid B.; Mohan, Swarna; Ratner, Deena; Reichelderfer, Patricia; Roberts, Paula; Shattock, Robin J.; Cummins, James E.

2009-01-01

Microbicide candidates with promising in vitro activity are often advanced for evaluations using human primary tissue explants relevant to the in vivo mucosal transmission of human immunodeficiency virus type 1 (HIV-1), such as tonsil, cervical, or rectal tissue. To compare virus growth or the anti-HIV-1 efficacies of candidate microbicides in tissue explants, a novel soft-endpoint method was evaluated to provide a single, objective measurement of virus growth. The applicability of the soft endpoint is shown across several different ex vivo tissue types, with the method performed in different laboratories, and for a candidate microbicide (PRO 2000). The soft-endpoint method was compared to several other endpoint methods, including (i) the growth of virus on specific days after infection, (ii) the area under the virus growth curve, and (iii) the slope of the virus growth curve. Virus growth at the assay soft endpoint was compared between laboratories, methods, and experimental conditions, using nonparametric statistical analyses. Intra-assay variability determinations using the coefficient of variation demonstrated higher variability for virus growth in rectal explants. Significant virus inhibition by PRO 2000 and significant differences in the growth of certain primary HIV-1 isolates were observed by the majority of laboratories. These studies indicate that different laboratories can provide consistent measurements of anti-HIV-1 microbicide efficacy when (i) the soft endpoint or another standardized endpoint is used, (ii) drugs and/or virus reagents are centrally sourced, and (iii) the same explant tissue type and method are used. Application of the soft-endpoint method reduces the inherent variability in comparisons of preclinical assays used for microbicide development. PMID:19726602

Benefit and harms of new anti-cancer drugs.

PubMed

Vera-Badillo, Francisco E; Al-Mubarak, Mustafa; Templeton, Arnoud J; Amir, Eitan

2013-06-01

Phase III randomized controlled trials (RCTs) assess clinically important differences in endpoints that reflect benefit to and harm of patients. Defining benefit of cancer drugs can be difficult. Overall survival and quality of life are the most relevant primary endpoints, but difficulty in measuring these mean that other endpoints are often used, although their surrogacy or clinical relevance has not always been established. In general, advances in drug development have led to numerous new drugs to enter the market. Pivotal RCT of several new drugs have shown that benefit appeared greater for targeted anticancer agents than for chemotherapeutic agents. This effect seems particularly evident with targeted agents evaluated in biomarker-driven studies. Unfortunately, new therapies have also shown an increase in toxicity. Such toxicity is not always evident in the initial reports of RCTs. This may be a result of a statistical inability to detect differences between arms of RCTs, or occasionally due to biased reporting. There are several examples where reports of new toxicities could only be found in drug labels. In some cases, the small improvement in survival has come at a cost of substantial excess toxicity, leading some to consider such therapy as having equipoise.

Comparison of the etiological relevance of Staphylococcus haemolyticus and Staphylococcus hominis.

PubMed

Frickmann, Hagen; Hahn, Andreas; Skusa, Romy; Mund, Nils; Viehweger, Vivian; Köller, Thomas; Köller, Kerstin; Schwarz, Norbert Georg; Becker, Karsten; Warnke, Philipp; Podbielski, Andreas

2018-05-19

The study was performed to assess potential differences in the etiological relevance of two coagulase-negative staphylococci (CoNS), Staphylococcus haemolyticus and Staphylococcus hominis, in an observational single-center study. Over a 5-year interval, patients in whom there was detected S. haemolyticus or S. hominis of presumed etiological relevance were assessed for the primary endpoint death during hospital stay and the secondary endpoint transfer to an intensive care unit (ICU) after the detection of S. haemolyticus or S. hominis. Patients with S. haemolyticus or S. hominis died in 11.3% (50 out of 444) and 9.5% (60 out of 631) of cases, respectively, and were transferred to ICU after S. haemolyticus and S. hominis detection in 8.7% (19 out of 219) and 11.7% (44 out of 377) of cases, respectively. There was no significance for species-related influence on the primary outcome parameter (P > 0.1), while ICU transfers were more likely for patients with S. hominis detections (P = 0.016). Delayed diagnosis of both CoNS species was associated with an increased probability of death (P = 0.009). The study revealed comparable morbidity caused by S. haemolyticus and S. hominis identified in a clinically relevant context.

Environmental risk assessment of triclosan and ibuprofen in marine sediments using individual and sub-individual endpoints.

PubMed

Pusceddu, F H; Choueri, R B; Pereira, C D S; Cortez, F S; Santos, D R A; Moreno, B B; Santos, A R; Rogero, J R; Cesar, A

2018-01-01

The guidelines for the Environmental Risk Assessment (ERA) of pharmaceuticals and personal care products (PPCP) recommend the use of standard ecotoxicity assays and the assessment of endpoints at the individual level to evaluate potential effects of PPCP on biota. However, effects at the sub-individual level can also affect the ecological fitness of marine organisms chronically exposed to PPCP. The aim of the current study was to evaluate the environmental risk of two PPCP in marine sediments: triclosan (TCS) and ibuprofen (IBU), using sub-individual and developmental endpoints. The environmental levels of TCS and IBU were quantified in marine sediments from the vicinities of the Santos submarine sewage outfall (Santos Bay, São Paulo, Brazil) at 15.14 and 49.0 ng g -1 , respectively. A battery (n = 3) of chronic bioassays (embryo-larval development) with a sea urchin (Lytechinus variegatus) and a bivalve (Perna perna) were performed using two exposure conditions: sediment-water interface and elutriates. Moreover, physiological stress through the Neutral Red Retention Time Assay (NRRT) was assessed in the estuarine bivalve Mytella charruana exposed to TCS and IBU spiked sediments. These compounds affected the development of L. variegatus and P. perna (75 ng g -1 for TCS and 15 ng g -1 for IBU), and caused a significant decrease in M. charruana lysosomal membrane stability at environmentally relevant concentrations (0.08 ng g -1 for TCS and 0.15 ng g -1 for IBU). Chemical and ecotoxicological data were integrated and the risk quotient estimated for TCS and IBU were higher than 1.0, indicating a high environmental risk of these compounds in sediments. These are the first data of sediment risk assessment of pharmaceuticals and personal care products of Latin America. In addition, the results suggest that the ERA based only on individual-level and standard toxicity tests may overlook other biological effects that can affect the health of marine organisms exposed to PPCP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessing off-site impacts of wildfires on aquatic organisms using in-situ assays

NASA Astrophysics Data System (ADS)

Ré, Ana; Saraiva, MariaJoão; Puga, João; Campos, Isabel; Pereira, Joana; Keizer, Jacob; Goncalves, Fernando; Abrantes, Nelson

2017-04-01

Wildfires have been recognized as an important source of diffuse pollution to aquatic systems, particularly through the production and transport of pyrolytic substances such as polycyclic aromatic hydrocarbons (PAHs) and metals associated to ash/soil loads. However, the effects of these compounds from recently burnt areas on the aquatic biota have been largely ignored. Hence, the main goal of this study was to assess the ecotoxicological effects of wildfires in aquatic systems through the use of in situ experiments. In this sense, five sites were selected in a catchment partially burnt: two in the main water course - Ceira river (Miranda do Corvo, Portugal), being one located upstream (RUS) and the other downstream (RDS) the burnt area; two in tributary streams within the burnt area (SUS and SDS); and finally one in a stream located in the unburnt part of the catchment (CS). During the first post-fire rainfall events, distinct organisms, including the water flea Daphnia magna, the freshwater shrimp Atyaephyra desmaresti, the freshwater clam Corbicula fluminea and the mosquitofish Gambusia holbrooki were exposed in situ, in all five sites, using dedicated test chambers. After four days of field exposition, the mortality and post-exposure feeding inhibition were evaluated. Feeding depression after exposure time was selected as a sub-lethal endpoint because it is a quick, sensitive and ecologically relevant indicator of toxic stress. The results showed negligible mortality for all the species and sites, thus lethality was not sensitive to discern impacts among the assessed sites. Conversely, the sub-lethal post-exposure feeding inhibition endpoint, revealed a decrease of feeding rate, in streams within the burnt area (SUS and SDS), that seemed to be the most affected places in the study area. Conversely, the sites outside the burnt area, both on river (RUS) and on the stream (CS), showed no adverse effects in this endpoint. Hence, the current results pointed-out that in situ bioassays were a suitable tool to assess the risks of wildfire to aquatic species and that the post-fire runoff rich in concerning substances as PAHs and metals can sub-lethally impair the aquatic organisms in water bodies located within or downstream the burnt area.

The Use of Surrogate Endpoints in Regulating Medicines for Cardio-Renal Disease: Opinions of Stakeholders

PubMed Central

Schievink, Bauke; Lambers Heerspink, Hiddo; Leufkens, Hubert; De Zeeuw, Dick; Hoekman, Jarno

2014-01-01

Aim There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic. Methods We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations) and medical specialties (cardiology or nephrology vs. other). Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use. Results Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9) or when there is an unmet clinical need (mean score: 3.8, SD: 1.2). Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP), HbA1c, albuminuria, CRP) for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1). Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints. Conclusion Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them. PMID:25268242

The use of surrogate endpoints in regulating medicines for cardio-renal disease: opinions of stakeholders.

PubMed

Schievink, Bauke; Lambers Heerspink, Hiddo; Leufkens, Hubert; De Zeeuw, Dick; Hoekman, Jarno

2014-01-01

There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic. We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations) and medical specialties (cardiology or nephrology vs. other). Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use. Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9) or when there is an unmet clinical need (mean score: 3.8, SD: 1.2). Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP), HbA1c, albuminuria, CRP) for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1). Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints. Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them.

Polycyclic aromatic hydrocarbon-induced signaling events relevant to inflammation and tumorigenesis in lung cells are dependent on molecular structure.

PubMed

Osgood, Ross S; Upham, Brad L; Hill, Thomas; Helms, Katherine L; Velmurugan, Kalpana; Babica, Pavel; Bauer, Alison K

2014-01-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental and occupational toxicants, which are a major human health concern in the U.S. and abroad. Previous research has focused on the genotoxic events caused by high molecular weight PAHs, but not on non-genotoxic events elicited by low molecular weight PAHs. We used an isomeric pair of low molecular weight PAHs, namely 1-Methylanthracene (1-MeA) and 2-Methylanthracene (2-MeA), in which only 1-MeA possessed a bay-like region, and hypothesized that 1-MeA, but not 2-MeA, would affect non-genotoxic endpoints relevant to tumor promotion in murine C10 lung cells, a non-tumorigenic type II alveolar pneumocyte and progenitor cell type of lung adenocarcinoma. The non-genotoxic endpoints assessed were dysregulation of gap junction intercellular communication function and changes in the major pulmonary connexin protein, connexin 43, using fluorescent redistribution and immunoblots, activation of mitogen activated protein kinases (MAPK) using phosphospecific MAPK antibodies for immunoblots, and induction of inflammatory genes using quantitative RT-PCR. 2-MeA had no effect on any of the endpoints, but 1-MeA dysregulated gap junctional communication in a dose and time dependent manner, reduced connexin 43 protein expression, and altered membrane localization. 1-MeA also activated ERK1/2 and p38 MAP kinases. Inflammatory genes, such as cyclooxygenase 2, and chemokine ligand 2 (macrophage chemoattractant 2), were also upregulated in response to 1-MeA only. These results indicate a possible structure-activity relationship of these low molecular weight PAHs relevant to non-genotoxic endpoints of the promoting aspects of cancer. Therefore, our novel findings may improve the ability to predict outcomes for future studies with additional toxicants and mixtures, identify novel targets for biomarkers and chemotherapeutics, and have possible implications for future risk assessment for these PAHs.

Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials

EPA Science Inventory

Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects. Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant ...

Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial

PubMed Central

BRISCO, MEREDITH A.; ZILE, MICHAEL R.; HANBERG, JENNIFER S.; WILSON, F. PERRY; PARIKH, CHIRAG R.; COCA, STEVEN G.; TANG, W.H. WILSON; TESTANI, JEFFREY M.

2017-01-01

Background Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies. Methods and Results We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial. WRF was defined as an increase in creatinine >0.3 mg/dL and improvement in renal function (IRF) as a decrease >0.3 mg/dL. When examining linear changes in creatinine from baseline to 72 hours (the coprimary endpoint of DOSE), increasing creatinine was associated with lower risk for the composite outcome (HR = 0.81 per 0.3 mg/dL increase, 95% CI 0.67–0.98, P = .026). Compared with patients with stable renal function (n = 219), WRF (n = 54) was not associated with the composite endpoint (HR = 1.17, 95% CI = 0.77–1.78, P = .47). However, compared with stable renal function, there was a strong relationship between IRF (n = 28) and the composite endpoint (HR = 2.52, 95% CI = 1.57–4.03, P <.001). Conclusion The coprimary endpoint of the DOSE trial, a linear increase in creatinine, was paradoxically associated with improved outcomes. This was driven by absence of risk attributable to WRF and a strong risk associated with IRF. These results argue against using changes in serum creatinine as a surrogate endpoint in trials of decongestive strategies. PMID:27374839

Muscle short-range stiffness can be used to estimate the endpoint stiffness of the human arm

PubMed Central

Hu, Xiao; Murray, Wendy M.

2011-01-01

The mechanical properties of the human arm are regulated to maintain stability across many tasks. The static mechanics of the arm can be characterized by estimates of endpoint stiffness, considered especially relevant for the maintenance of posture. At a fixed posture, endpoint stiffness can be regulated by changes in muscle activation, but which activation-dependent muscle properties contribute to this global measure of limb mechanics remains unclear. We evaluated the role of muscle properties in the regulation of endpoint stiffness by incorporating scalable models of muscle stiffness into a three-dimensional musculoskeletal model of the human arm. Two classes of muscle models were tested: one characterizing short-range stiffness and two estimating stiffness from the slope of the force-length curve. All models were compared with previously collected experimental data describing how endpoint stiffness varies with changes in voluntary force. Importantly, muscle properties were not fit to the experimental data but scaled only by the geometry of individual muscles in the model. We found that force-dependent variations in endpoint stiffness were accurately described by the short-range stiffness of active arm muscles. Over the wide range of evaluated arm postures and voluntary forces, the musculoskeletal model incorporating short-range stiffness accounted for 98 ± 2, 91 ± 4, and 82 ± 12% of the variance in stiffness orientation, shape, and area, respectively, across all simulated subjects. In contrast, estimates based on muscle force-length curves were less accurate in all measures, especially stiffness area. These results suggest that muscle short-range stiffness is a major contributor to endpoint stiffness of the human arm. Furthermore, the developed model provides an important tool for assessing how the nervous system may regulate endpoint stiffness via changes in muscle activation. PMID:21289133

Landscape pattern metrics and regional assessment

USGS Publications Warehouse

O'Neill, R. V.; Riitters, K.H.; Wickham, J.D.; Jones, K.B.

1999-01-01

The combination of remote imagery data, geographic information systems software, and landscape ecology theory provides a unique basis for monitoring and assessing large-scale ecological systems. The unique feature of the work has been the need to develop and interpret quantitative measures of spatial pattern-the landscape indices. This article reviews what is known about the statistical properties of these pattern metrics and suggests some additional metrics based on island biogeography, percolation theory, hierarchy theory, and economic geography. Assessment applications of this approach have required interpreting the pattern metrics in terms of specific environmental endpoints, such as wildlife and water quality, and research into how to represent synergystic effects of many overlapping sources of stress.

Evidence for the use of parenteral nutrition in the pediatric intensive care unit.

PubMed

Fivez, Tom; Kerklaan, Dorian; Mesotten, Dieter; Verbruggen, Sascha; Joosten, Koen; Van den Berghe, Greet

2017-02-01

During hospitalization in a pediatric intensive care unit (PICU), critically ill children are fed artificially. Administered via the preferred enteral route, caloric targets are often not reached. Hence, parenteral nutrition is given to this patient population. In this review we analyzed the available evidence from randomized controlled trials (RCTs) that supports the use of parenteral nutrition in children during critical illness. A search strategy in Ovid MEDLINE and Ovid EMBASE was created and trial registries were screened to identify the relevant RCTs. Studies were included if they were randomized controlled trials, involved pediatric patients admitted to PICU, and compared different dosing/compositions of parenteral nutrition. Descriptive studies and reviews were excluded. Of the 584 articles identified by the search strategy, only 114 articles were retained after title screening. Further abstract and full text screening identified 6 small RCTs that compared two dosing/composition strategies of parenteral nutrition. These trials reported differences in surrogate endpoints without an effect on hard clinical endpoints. The RCTs observed improvements in these surrogate endpoints with the use of more calories or when parenteral glutamine or fish oil was added. The few RCTs suggest that surrogate endpoints can be affected by providing parenteral nutrition to critically ill children, but the studies were not statistically powered to draw meaningful clinical conclusions. Large RCTs with clinically relevant outcome measures are urgently needed to support the current nutritional guidelines that advise the use of parenteral nutrition in the PICU. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

USE OF ECOLOGICAL REGIONS IN AQUATIC ASSESSMENTS OF ECOLOGICAL CONDITION

EPA Science Inventory

Ecological regions are areas of similar climate, landform, soil, potential natural vegetation, hydrology, or other ecologically relevant variables. The makeup of aquatic biological assemblages (e.g., fish, macroinvertebrates, algae, riparian birds, etc.) varies dramatically over ...

ECOLOGICALLY-RELEVANT QUANTIFICATION OF STREAMFLOW REGIMES IN WESTERN STREAMS

EPA Science Inventory

This report describes the rationale for and application of a protocol for estimation of ecologically-relevant streamflow metrics that quantify streamflow regime for ungaged sites subject to a range of human impact. The analysis presented here is focused on sites sampled by the U....

Treatment of Men for “Low Testosterone”: A Systematic Review

PubMed Central

Huo, Samantha; Scialli, Anthony R.; McGarvey, Sean; Hill, Elizabeth; Tügertimur, Buğra; Hogenmiller, Alycia; Hirsch, Alessandra I.; Fugh-Berman, Adriane

2016-01-01

Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of “low testosterone” (low-T) for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition. We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables. Testosterone supplementation did not show consistent benefit for cardiovascular risk, sexual function, mood and behavior, or cognition. Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo. Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido. Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function. Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality, psychological well-being, or mood. The prescription of testosterone supplementation for low-T for cardiovascular health, sexual function, physical function, mood, or cognitive function is without support from randomized clinical trials. PMID:27655114

Assessing combined impacts of agrochemicals: Aquatic macroinvertebrate population responses in outdoor mesocosms.

PubMed

Barmentlo, S Henrik; Schrama, Maarten; Hunting, Ellard R; Heutink, Roel; van Bodegom, Peter M; de Snoo, Geert R; Vijver, Martina G

2018-08-01

Agricultural ditches host a diverse community of species. These species often are unwarrantedly exposed to fertilizers and a wide-array of pesticides (hereafter: agrochemicals). Standardized ecotoxicological research provides valuable information to predict whether these pesticides possibly pose a threat to the organisms living within these ditches, in particular macro-invertebrates. However, knowledge on how mixtures of these agrochemicals affect macro-invertebrates under realistic abiotic conditions and with population and community complexity is mostly lacking. Therefore we examined here, using a full factorial design, the population responses of macroinvertebrate species assemblages exposed to environmentally relevant concentrations of three commonly used agrochemicals (for 35days) in an outdoor experiment. The agrochemicals selected were an insecticide (imidacloprid), herbicide (terbuthylazine) and nutrients (NPK), all having a widespread usage and often detected together in watersheds. Effects on species abundance and body length caused by binary mixture combinations could be described from single substance exposure. However, when agrochemicals were applied as tertiary mixtures, as they are commonly found in agricultural waters, species' abundance often deviated from expectations made based on the three single treatments. This indicates that pesticide-mixture induced toxicity to population relevant endpoints are difficult to extrapolate to field conditions. As in agricultural ditches often a multitude (approx. up to 7) of agrochemicals residues are detected, we call other scientist to verify the ecological complexity of non-additive induced shifts in natural aquatic invertebrate populations and aquatic species assemblages. Copyright © 2018 Elsevier B.V. All rights reserved.

The relevance of dietary sodium in hemodialysis

PubMed Central

Mc Causland, Finnian R.; Waikar, Sushrut S.; Brunelli, Steven M.

2013-01-01

Since the earliest days of hemodialysis, dietary sodium restriction has been recommended as a therapeutic means to mitigate problems of extracellular volume overload, hypertension and inter-dialytic weight gain. Recently, there has been a proliferation of human subjects' research examining the potential effects of dietary sodium curtailment. Herein we examine the available evidence with respect to the effects of dietary sodium restriction on clinically relevant endpoints among hemodialysis patients. PMID:23129821

Development of ecological indicator guilds for land management

USGS Publications Warehouse

Krzysik, A.J.; Balbach, H.E.; Duda, J.J.; Emlen, J.M.; Freeman, D.C.; Graham, J.H.; Kovacic, D.A.; Smith, L.M.; Zak, J.C.

2005-01-01

Agency land-use must be efficiently and cost-effectively monitored to assess conditions and trends in ecosystem processes and natural resources relevant to mission requirements and legal mandates. Ecological Indicators represent important land management tools for tracking ecological changes and preventing irreversible environmental damage in disturbed landscapes. The overall objective of the research was to develop both individual and integrated sets (i.e., statistically derived guilds) of Ecological Indicators to: quantify habitat conditions and trends, track and monitor ecological changes, provide early warning or threshold detection, and provide guidance for land managers. The derivation of Ecological Indicators was based on statistical criteria, ecosystem relevance, reliability and robustness, economy and ease of use for land managers, multi-scale performance, and stress response criteria. The basis for the development of statistically based Ecological Indicators was the identification of ecosystem metrics that analytically tracked a landscape disturbance gradient.

Human Ecology: Persistence and Change.

ERIC Educational Resources Information Center

Hawley, Amos H.

1981-01-01

Demonstrates the relevance of ecology to sociological research and discusses some of the theoretical perspectives embodied in ecology. Examines ecology's emphasis upon the population rather than the individual as the unit of observation and on organizations as products of the interaction of population and environment. (DB)

Heavy Metals in ToxCast: Relevance to Food Safety (SOT)

EPA Science Inventory

Human exposure to heavy metals occurs through food contamination due to industrial processes, vehicle emissions and farming methods. Specific toxicity endpoints have been associated with metal exposures, e.g. lead and neurotoxicity; however, numerous varieties of heavy metals hav...

Evaluating the Toxicity of Cigarette Whole Smoke Solutions in an Air-Liquid-Interface Human In Vitro Airway Tissue Model.

PubMed

Cao, Xuefei; Muskhelishvili, Levan; Latendresse, John; Richter, Patricia; Heflich, Robert H

2017-03-01

Exposure to cigarette smoke causes a multitude of pathological changes leading to tissue damage and disease. Quantifying such changes in highly differentiated in vitro human tissue models may assist in evaluating the toxicity of tobacco products. In this methods development study, well-differentiated human air-liquid-interface (ALI) in vitro airway tissue models were used to assess toxicological endpoints relevant to tobacco smoke exposure. Whole mainstream smoke solutions (WSSs) were prepared from 2 commercial cigarettes (R60 and S60) that differ in smoke constituents when machine-smoked under International Organization for Standardization conditions. The airway tissue models were exposed apically to WSSs 4-h per day for 1-5 days. Cytotoxicity, tissue barrier integrity, oxidative stress, mucin secretion, and matrix metalloproteinase (MMP) excretion were measured. The treatments were not cytotoxic and had marginal effects on tissue barrier properties; however, other endpoints responded in time- and dose-dependent manners, with the R60 resulting in higher levels of response than the S60 for many endpoints. Based on the lowest effect dose, differences in response to the WSSs were observed for mucin induction and MMP secretion. Mitigation of mucin induction by cotreatment of cultures with N-acetylcysteine suggests that oxidative stress contributes to mucus hypersecretion. Overall, these preliminary results suggest that quantifying disease-relevant endpoints using ALI airway models is a potential tool for tobacco product toxicity evaluation. Additional research using tobacco samples generated under smoking machine conditions that more closely approximate human smoking patterns will inform further methods development. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the public domain in the US.

A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine

PubMed Central

KOTLER, MOSHE; DILBAZ, NESRIN; ROSA, FERNANDA; PATERAKIS, PERIKLIS; MILANOVA, VIHRA; SMULEVICH, ANATOLY B.; LAHAYE, MARJOLEIN

2016-01-01

Objective: The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER). Methods: Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a ≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of ≤5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change. Results: Of 396 patients, 65.2% were men, mean age was 40.0±12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of ≥20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8±5.2 kg at endpoint, and a clinically relevant weight gain of ≥7% occurred in 8.0% of patients. Conclusion: Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine. PMID:26813484

A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine.

PubMed

Kotler, Moshe; Dilbaz, Nesrin; Rosa, Fernanda; Paterakis, Periklis; Milanova, Vihra; Smulevich, Anatoly B; Lahaye, Marjolein; Schreiner, Andreas

2016-01-01

The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER). Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of ≤ 5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change. Of 396 patients, 65.2% were men, mean age was 40.0 ± 12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of ≥ 20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8 ± 5.2 kg at endpoint, and a clinically relevant weight gain of ≥ 7% occurred in 8.0% of patients. Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine.

A systematic comparison of recurrent event models for application to composite endpoints.

PubMed

Ozga, Ann-Kathrin; Kieser, Meinhard; Rauch, Geraldine

2018-01-04

Many clinical trials focus on the comparison of the treatment effect between two or more groups concerning a rarely occurring event. In this situation, showing a relevant effect with an acceptable power requires the observation of a large number of patients over a long period of time. For feasibility issues, it is therefore often considered to include several event types of interest, non-fatal or fatal, and to combine them within a composite endpoint. Commonly, a composite endpoint is analyzed with standard survival analysis techniques by assessing the time to the first occurring event. This approach neglects that an individual may experience more than one event which leads to a loss of information. As an alternative, composite endpoints could be analyzed by models for recurrent events. There exists a number of such models, e.g. regression models based on count data or Cox-based models such as the approaches of Andersen and Gill, Prentice, Williams and Peterson or, Wei, Lin and Weissfeld. Although some of the methods were already compared within the literature there exists no systematic investigation for the special requirements regarding composite endpoints. Within this work a simulation-based comparison of recurrent event models applied to composite endpoints is provided for different realistic clinical trial scenarios. We demonstrate that the Andersen-Gill model and the Prentice- Williams-Petersen models show similar results under various data scenarios whereas the Wei-Lin-Weissfeld model delivers effect estimators which can considerably deviate under commonly met data scenarios. Based on the conducted simulation study, this paper helps to understand the pros and cons of the investigated methods in the context of composite endpoints and provides therefore recommendations for an adequate statistical analysis strategy and a meaningful interpretation of results.

ECVAM and new technologies for toxicity testing.

PubMed

Bouvier d'Yvoire, Michel; Bremer, Susanne; Casati, Silvia; Ceridono, Mara; Coecke, Sandra; Corvi, Raffaella; Eskes, Chantra; Gribaldo, Laura; Griesinger, Claudius; Knaut, Holger; Linge, Jens P; Roi, Annett; Zuang, Valérie

2012-01-01

The development of alternative empirical (testing) and non-empirical (non-testing) methods to traditional toxicological tests for complex human health effects is a tremendous task. Toxicants may potentially interfere with a vast number of physiological mechanisms thereby causing disturbances on various levels of complexity of human physiology. Only a limited number of mechanisms relevant for toxicity ('pathways' of toxicity) have been identified with certainty so far and, presumably, many more mechanisms by which toxicants cause adverse effects remain to be identified. Recapitulating in empirical model systems (i.e., in vitro test systems) all those relevant physiological mechanisms prone to be disturbed by toxicants and relevant for causing the toxicity effect in question poses an enormous challenge. First, the mechanism(s) of action of toxicants in relation to the most relevant adverse effects of a specific human health endpoint need to be identified. Subsequently, these mechanisms need to be modeled in reductionist test systems that allow assessing whether an unknown substance may operate via a specific (array of) mechanism(s). Ideally, such test systems should be relevant for the species of interest, i.e., based on human cells or modeling mechanisms present in humans. Since much of our understanding about toxicity mechanisms is based on studies using animal model systems (i.e., experimental animals or animal-derived cells), designing test systems that model mechanisms relevant for the human situation may be limited by the lack of relevant information from basic research. New technologies from molecular biology and cell biology, as well as progress in tissue engineering, imaging techniques and automated testing platforms hold the promise to alleviate some of the traditional difficulties associated with improving toxicity testing for complex endpoints. Such new technologies are expected (1) to accelerate the identification of toxicity pathways with human relevance that need to be modeled in test methods for toxicity testing (2) to enable the reconstruction of reductionist test systems modeling at a reduced level of complexity the target system/organ of interest (e.g., through tissue engineering, use of human-derived cell lines and stem cells etc.), (3) to allow the measurement of specific mechanisms relevant for a given health endpoint in such test methods (e.g., through gene and protein expression, changes in metabolites, receptor activation, changes in neural activity etc.), (4) to allow to measure toxicity mechanisms at higher throughput rates through the use of automated testing. In this chapter, we discuss the potential impact of new technologies on the development, optimization and use of empirical testing methods, grouped according to important toxicological endpoints. We highlight, from an ECVAM perspective, the areas of topical toxicity, skin absorption, reproductive and developmental toxicity, carcinogenicity/genotoxicity, sensitization, hematopoeisis and toxicokinetics and discuss strategic developments including ECVAM's database service on alternative methods. Neither the areas of toxicity discussed nor the highlighted new technologies represent comprehensive listings which would be an impossible endeavor in the context of a book chapter. However, we feel that these areas are of utmost importance and we predict that new technologies are likely to contribute significantly to test development in these fields. We summarize which new technologies are expected to contribute to the development of new alternative testing methods over the next few years and point out current and planned ECVAM projects for each of these areas.

Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial.

PubMed

Vinereanu, Dragos; Stevens, Susanna R; Alexander, John H; Al-Khatib, Sana M; Avezum, Alvaro; Bahit, Marıa Cecilia; Granger, Christopher B; Lopes, Renato D; Halvorsen, Sigrun; Hanna, Michael; Husted, Steen; Hylek, Elaine M; Mărgulescu, Andrei D; Wallentin, Lars; Atar, Dan

2015-12-07

To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation. Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex. In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women. ARISTOTLE ClinicalTrials.gov number, NCT00412984. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Using Algal Metrics and Biomass to Evaluate Multiple Ways of Defining Concentration-Based Nutrient Criteria in Streams and their Ecological Relevance

EPA Science Inventory

We examined the utility of nutrient criteria derived solely from total phosphorus (TP) concentrations in streams (regression models and percentile distributions) and evaluated their ecological relevance to diatom and algal biomass responses. We used a variety of statistics to cha...

[Ecological risk assessment of land use based on exploratory spatial data analysis (ESDA): a case study of Haitan Island, Fujian Province].

PubMed

Wu, Jian; Chen, Peng; Wen, Chao-Xiang; Fu, Shi-Feng; Chen, Qing-Hui

2014-07-01

As a novel environment management tool, ecological risk assessment has provided a new perspective for the quantitative evaluation of ecological effects of land-use change. In this study, Haitan Island in Fujian Province was taken as a case. Based on the Landsat TM obtained in 1990, SPOT5 RS images obtained in 2010, general layout planning map of Pingtan Comprehensive Experimental Zone in 2030, as well as the field investigation data, we established an ecological risk index to measure ecological endpoints. By using spatial autocorrelation and semivariance analysis of Exploratory Spatial Data Analysis (ESDA), the ecological risk of Haitan Island under different land-use situations was assessed, including the past (1990), present (2010) and future (2030), and the potential risk and its changing trend were analyzed. The results revealed that the ecological risk index showed obvious scale effect, with strong positive correlation within 3000 meters. High-high (HH) and low-low (LL) aggregations were predominant types in spatial distribution of ecological risk index. The ecological risk index showed significant isotropic characteristics, and its spatial distribution was consistent with Anselin Local Moran I (LISA) distribution during the same period. Dramatic spatial distribution change of each ecological risk area was found among 1990, 2010 and 2030, and the fluctuation trend and amplitude of different ecological risk areas were diverse. The low ecological risk area showed a rise-to-fall trend while the medium and high ecological risk areas showed a fall-to-rise trend. In the planning period, due to intensive anthropogenic disturbance, the high ecological risk area spread throughout the whole region. To reduce the ecological risk in land-use and maintain the regional ecological security, the following ecological risk control strategies could be adopted, i.e., optimizing the spatial pattern of land resources, protecting the key ecoregions and controlling the scale of construction land use.

Comparison of reference doses (RfDs) developed for the protection of wildlife species in contrast to humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valoppi, L.; Carlisle, J.; Polisini, J.

1995-12-31

A component of both human health and ecological risk assessments is the evaluation of toxicity values. A comparison between the methodology for the development of Reference Doses (RfDs) to be protective of humans, and that developed for vertebrate wildlife species is presented. For all species, a chronic No Observable Adverse Effect Level (NOAEL) is developed by applying uncertainty factors (UFs) to literature-based toxicity values. Uncertainty factors are used to compensate for the length of exposure, sensitivity of endpoints, and cross-species extrapolations between the test species and the species being assessed. Differences between human and wildlife species could include the toxicologicalmore » endpoint, the critical study, and the magnitude of the cross-species extrapolation factor. Case studies for select chemicals are presented which contrast RfDs developed for humans and those developed for avian and mammalian wildlife.« less

Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial.

PubMed

Brisco, Meredith A; Zile, Michael R; Hanberg, Jennifer S; Wilson, F Perry; Parikh, Chirag R; Coca, Steven G; Tang, W H Wilson; Testani, Jeffrey M

2016-10-01

Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies. We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial. WRF was defined as an increase in creatinine >0.3 mg/dL and improvement in renal function (IRF) as a decrease >0.3 mg/dL. When examining linear changes in creatinine from baseline to 72 hours (the coprimary endpoint of DOSE), increasing creatinine was associated with lower risk for the composite outcome (HR = 0.81 per 0.3 mg/dL increase, 95% CI 0.67-0.98, P = .026). Compared with patients with stable renal function (n = 219), WRF (n = 54) was not associated with the composite endpoint (HR = 1.17, 95% CI = 0.77-1.78, P = .47). However, compared with stable renal function, there was a strong relationship between IRF (n = 28) and the composite endpoint (HR = 2.52, 95% CI = 1.57-4.03, P < .001). The coprimary endpoint of the DOSE trial, a linear increase in creatinine, was paradoxically associated with improved outcomes. This was driven by absence of risk attributable to WRF and a strong risk associated with IRF. These results argue against using changes in serum creatinine as a surrogate endpoint in trials of decongestive strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

A guide to statistical analysis in microbial ecology: a community-focused, living review of multivariate data analyses.

PubMed

Buttigieg, Pier Luigi; Ramette, Alban

2014-12-01

The application of multivariate statistical analyses has become a consistent feature in microbial ecology. However, many microbial ecologists are still in the process of developing a deep understanding of these methods and appreciating their limitations. As a consequence, staying abreast of progress and debate in this arena poses an additional challenge to many microbial ecologists. To address these issues, we present the GUide to STatistical Analysis in Microbial Ecology (GUSTA ME): a dynamic, web-based resource providing accessible descriptions of numerous multivariate techniques relevant to microbial ecologists. A combination of interactive elements allows users to discover and navigate between methods relevant to their needs and examine how they have been used by others in the field. We have designed GUSTA ME to become a community-led and -curated service, which we hope will provide a common reference and forum to discuss and disseminate analytical techniques relevant to the microbial ecology community. © 2014 The Authors. FEMS Microbiology Ecology published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

Ecological Approaches to Understanding Human Crowding.

ERIC Educational Resources Information Center

Baron, Reuben M.

1979-01-01

Characteristics of the ecological approach to perception are presented. The affordance concept and its relevance is emphasized. Human crowding is discussed in affordance terms. There is a comparison given between present affordance analysis and ecological analysis. (Author/SA)

ToxRefDB: Classifying ToxCast™ Phase I Chemicals Utilizing Structured Toxicity Information

EPA Science Inventory

There is an essential need for highly detailed chemicals classifications within the ToxCast™ research program. In order to develop predictive models and biological signatures utilizing high-throughput screening (HTS) and in vitro genomic data, relevant endpoints and toxicities m...

What data should we collect? A framework for identifying indicators of ecosystem contributions to human well being

EPA Science Inventory

Ecological data enable a range of policy relevant analyses; the right ecological data enable ecosystem analyses to be linked to human well being making them more relevant and useful. The challenge we address is how to identify the right data. Our approach, founded on the “final e...

In Vitro Susceptibility Testing Methods for Caspofungin against Aspergillus and Fusarium Isolates

PubMed Central

Arikan, Sevtap; Lozano-Chiu, Mario; Paetznick, Victor; Rex, John H.

2001-01-01

We investigated the relevance of prominent reduction in turbidity macroscopically (MIC) and formation of aberrant hyphal tips microscopically (minimum effective concentration; MEC) in measuring the in vitro activity of caspofungin against Aspergillus and Fusarium. Caspofungin generated low MICs and MECs against Aspergillus, but not for Fusarium. While MICs increased inconsistently when the incubation time was prolonged, MEC appeared as a stable and potentially relevant endpoint in testing in vitro caspofungin activity. PMID:11120990

PREFACE: MARINE AND COASTAL APPLICATIONS IN LANDSCAPE ECOLOGY

EPA Science Inventory

Landscape ecology traditionally has been limited to the study of terrestrial systems; however, the questions and methods defining the science are equally relevant for marine and coastal systems. The reciprocal relationship between spatial pattern and ecological processes and the...

Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats.

PubMed

Sufka, Kenneth J; Staszko, Stephanie M; Johnson, Ainslee P; Davis, Morgan E; Davis, Rachel E; Smitherman, Todd A

2016-01-01

This research sought to further validate the rat nitroglycerin (NTG) migraine model by comparing the effects of single versus recurrent NTG episodes on behavioral endpoints that mirror ICHD-3 diagnostic criteria for migraine, and to determine if the altered behavioral endpoints are reduced after administration of sumatriptan. Separate cohorts of rats were administered NTG (10 mg/kg/2 ml) or saline (Experiment 1: single injection; Experiment 2: repeated injections; Experiment 3: repeated injections with sumatriptan [0.0, 0.3 and 1.0 mg/kg/ml] rescue. Behavioral endpoints were assessed 2 h after final NTG administration and included time in light/dark chambers for photophobia and activity, pain facial ratings, and cool (5 °C) and warm (46 °C) tail dip. The first two experiments demonstrated that repeated (n = 5) but not single NTG injections produced photophobia, decreased activity, and yielded less weight gain than saline injections. Experiment 3 showed that sumatriptan attenuated hypoactivity, reduced facial expressions of pain, and reversed weight alterations in a dose-dependent manner. These findings identify numerous clinical homologies of a recurrent NTG rat migraine model that may be useful for screening novel pharmacotherapies.

Combining censored and uncensored data in a U-statistic: design and sample size implications for cell therapy research.

PubMed

Moyé, Lemuel A; Lai, Dejian; Jing, Kaiyan; Baraniuk, Mary Sarah; Kwak, Minjung; Penn, Marc S; Wu, Colon O

2011-01-01

The assumptions that anchor large clinical trials are rooted in smaller, Phase II studies. In addition to specifying the target population, intervention delivery, and patient follow-up duration, physician-scientists who design these Phase II studies must select the appropriate response variables (endpoints). However, endpoint measures can be problematic. If the endpoint assesses the change in a continuous measure over time, then the occurrence of an intervening significant clinical event (SCE), such as death, can preclude the follow-up measurement. Finally, the ideal continuous endpoint measurement may be contraindicated in a fraction of the study patients, a change that requires a less precise substitution in this subset of participants.A score function that is based on the U-statistic can address these issues of 1) intercurrent SCE's and 2) response variable ascertainments that use different measurements of different precision. The scoring statistic is easy to apply, clinically relevant, and provides flexibility for the investigators' prospective design decisions. Sample size and power formulations for this statistic are provided as functions of clinical event rates and effect size estimates that are easy for investigators to identify and discuss. Examples are provided from current cardiovascular cell therapy research.

Using toxicokinetic-toxicodynamic modeling as an acute risk assessment refinement approach in vertebrate ecological risk assessment.

PubMed

Ducrot, Virginie; Ashauer, Roman; Bednarska, Agnieszka J; Hinarejos, Silvia; Thorbek, Pernille; Weyman, Gabriel

2016-01-01

Recent guidance identified toxicokinetic-toxicodynamic (TK-TD) modeling as a relevant approach for risk assessment refinement. Yet, its added value compared to other refinement options is not detailed, and how to conduct the modeling appropriately is not explained. This case study addresses these issues through 2 examples of individual-level risk assessment for 2 hypothetical plant protection products: 1) evaluating the risk for small granivorous birds and small omnivorous mammals of a single application, as a seed treatment in winter cereals, and 2) evaluating the risk for fish after a pulsed treatment in the edge-of-field zone. Using acute test data, we conducted the first tier risk assessment as defined in the European Food Safety Authority (EFSA) guidance. When first tier risk assessment highlighted a concern, refinement options were discussed. Cases where the use of models should be preferred over other existing refinement approaches were highlighted. We then practically conducted the risk assessment refinement by using 2 different models as examples. In example 1, a TK model accounting for toxicokinetics and relevant feeding patterns in the skylark and in the wood mouse was used to predict internal doses of the hypothetical active ingredient in individuals, based on relevant feeding patterns in an in-crop situation, and identify the residue levels leading to mortality. In example 2, a TK-TD model accounting for toxicokinetics, toxicodynamics, and relevant exposure patterns in the fathead minnow was used to predict the time-course of fish survival for relevant FOCUS SW exposure scenarios and identify which scenarios might lead to mortality. Models were calibrated using available standard data and implemented to simulate the time-course of internal dose of active ingredient or survival for different exposure scenarios. Simulation results were discussed and used to derive the risk assessment refinement endpoints used for decision. Finally, we compared the "classical" risk assessment approach with the model-based approach. These comparisons showed that TK and TK-TD models can bring more realism to the risk assessment through the possibility to study realistic exposure scenarios and to simulate relevant mechanisms of effects (including delayed toxicity and recovery). Noticeably, using TK-TD models is currently the most relevant way to directly connect realistic exposure patterns to effects. We conclude with recommendations on how to properly use TK and TK-TD model in acute risk assessment for vertebrates. © 2015 SETAC.

Advancing the surgical implantation of electronic tags in fish: a gap analysis and research agenda based on a review of trends in intracoelomic tagging effects studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooke, Steven J.; Woodley, Christa M.; Eppard, M. B.

2011-03-08

Early approaches to surgical implantation of electronic tags in fish were often through trial and error, however, in recent years there has been an interest in using scientific research to identify techniques and procedures that improve the outcome of surgical procedures and determine the effects of tagging on individuals. Here we summarize the trends in 108 peer-reviewed electronic tagging effect studies focused on intracoleomic implantation to determine opportunities for future research. To date, almost all of the studies have been conducted in freshwater, typically in laboratory environments, and have focused on biotelemetry devices. The majority of studies have focused onmore » salmonids, cyprinids, ictalurids and centrarchids, with a regional bias towards North America, Europe and Australia. Most studies have focused on determining whether there is a negative effect of tagging relative to control fish, with proportionally fewer that have contrasted different aspects of the surgical procedure (e.g., methods of sterilization, incision location, wound closure material) that could advance the discipline. Many of these studies included routine endpoints such as mortality, growth, healing and tag retention, with fewer addressing sublethal measures such as swimming ability, predator avoidance, physiological costs, or fitness. Continued research is needed to further elevate the practice of electronic tag implantation in fish in order to ensure that the data generated are relevant to untagged conspecifics (i.e., no long-term behavioural or physiological consequences) and the surgical procedure does not impair the health and welfare status of the tagged fish. To that end, we advocate for i) rigorous controlled manipulations based on statistical designs that have adequate power, account for inter-individual variation, and include controls and shams, ii) studies that transcend the laboratory and the field with more studies in marine waters, iii) incorporation of knowledge and techniques emerging from the medical and veterinary disciplines, iv) addressing all components of the surgical event, v) comparative studies that evaluate the same surgical techniques on multiple species and in different environments, vi) consideration of how biotic factors (e.g., sex, age, size) influence tagging outcomes, and vii) studies that cover a range of endpoints over ecologically-relevant time periods.« less

A strategy to facilitate cleanup at the Mare Island Naval Station

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins, J.; Albert, D.

1995-12-31

A strategy based on an early realistic estimation of ecological risk was devised to facilitate cleanup of installation restoration units at the Mare Island Naval Station. The strategy uses the results of 100 years of soil-plant studies, which centered on maximizing the bioavailability of nutrients for crop growth. The screening strategy classifies sites according to whether they present (1) little or no ecological risk and require no further action, (2) an immediate and significant risk, and (3) an ecological risk that requires further quantification. The strategy assumes that the main focus of screening level risk assessment is quantification of themore » potential for abiotic-to-biotic transfer (bioavailability) of contaminants, especially at lower trophic levels where exposure is likely to be at a maximum. Sediment screening criteria developed by the California Environmental Protection Agency is used as one regulatory endpoint for evaluating total chemical concentrations. A realistic estimation of risk is then determined by estimating the bioavailability of contaminants.« less

Using Quantitative Structure-Activity Relationship Modeling to Quantitatively Predict the Developmental Toxicity of Halogenated Azole compounds

EPA Science Inventory

Developmental toxicity is a relevant endpoint for the comprehensive assessment of human health risk from chemical exposure. However, animal developmental toxicity studies remain unavailable for many environmental contaminants due to the complexity and cost of these types of analy...

In Silico Prediction of Toxicokinetic Parameters for Environmentally Relevant Chemicals for Risk-Based Prioritization

EPA Science Inventory

Toxicokinetic (TK) models can address an important component of chemical risk assessments by helping bridge the gap between chemical exposure and measured toxicity endpoints. The metabolic clearance rate (CLint) and fraction of a chemical unbound by plasma proteins (Fub) are crit...

On developing bioindicators for human and ecological health.

PubMed

Burger, J; Gochfeld, M

2001-01-01

Risk assessors and risk managers generally either examine ecological health (using bioindicators) or human health (using biomarkers of exposure or effect). In this paper we suggest that it is possible and advantageous to develop bioindicators that can be used to assess exposure and effect for both human and non-human receptors. We describe the characteristics of suitable bioindicators for both human and ecological health, using mourning doves (Zenaida macroura), raccoons (Procyon lotor), and bluefish (Pomatomus saltatrix) as examples, and list the general characteristics of other species that would make them useful indicators for assessing both human and ecological health. Bioindicators can be used cross-sectionally to assess the status of ecosystems and risk as well as longitudinally for monitoring changes or evaluating remediation. For both human and ecological risk assessment, there are three sets of characteristics to consider when selecting bioindicators: biological relevance, methodological relevance, and societal relevance. An indicator which fails to fulfill these is not likely to be considered cost-effective and is likely to be abandoned. The indicator should be readily measured and must measure an important range of impacts. For long-term support of a bioindicator, the indicator should be easily understood, and be cost effective. We suggest that bioindicators that can also be used for both ecological and human health risk assessment are optimal.

Ecological risk assessment of TBT in Ise Bay.

PubMed

Yamamoto, Joji; Yonezawa, Yoshitaka; Nakata, Kisaburo; Horiguchi, Fumio

2009-02-01

An ecological risk assessment of tributyltin (TBT) in Ise Bay was conducted using the margin of exposure (MOE) method. The assessment endpoint was defined to protect the survival, growth and reproduction of marine organisms. Sources of TBT in this study were assumed to be commercial vessels in harbors and navigation routes. Concentrations of TBT in Ise Bay were estimated using a three-dimensional hydrodynamic model, an ecosystem model and a chemical fate model. Estimated MOEs for marine organisms for 1990 and 2008 were approximately 0.1-2.0 and over 100 respectively, indicating a declining temporal trend in the probability of adverse effects. The chemical fate model predicts a much longer persistence of TBT in sediments than in the water column. Therefore, it is necessary to monitor the harmful effects of TBT on benthic organisms.

Transmissible cancers in an evolutionary context.

PubMed

Ujvari, Beata; Papenfuss, Anthony T; Belov, Katherine

2016-07-01

Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro-environment and macro-environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro-environment and macro-environment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their micro-environment and macro-environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for the prevention and treatment of both contagious and non-communicable cancers. © 2016 The Authors. BioEssays published by WILEY Periodicals, Inc.

Effects of the antibiotic enrofloxacin on the ecology of tropical eutrophic freshwater microcosms.

PubMed

Rico, Andreu; Dimitrov, Mauricio R; Van Wijngaarden, René P A; Satapornvanit, Kriengkrai; Smidt, Hauke; Van den Brink, Paul J

2014-02-01

The main objective of the present study was to assess the ecological impacts of the fluoroquinolone antibiotic enrofloxacin on the structure and functioning of tropical freshwater ecosystems. Enrofloxacin was applied at a concentration of 1, 10, 100 and 1,000 μg/L for 7 consecutive days in 600-L outdoor microcosms in Thailand. The ecosystem-level effects of enrofloxacin were monitored on five structural (macroinvertebrates, zooplankton, phytoplankton, periphyton and bacteria) and two functional (organic matter decomposition and nitrogen cycling) endpoint groups for 4 weeks after the last antibiotic application. Enrofloxacin was found to dissipate relatively fast from the water column (half-dissipation time: 11.7h), and about 11% of the applied dose was transformed into its main by-product ciprofloxacin after 24h. Consistent treatment-related effects on the invertebrate and primary producer communities and on organic matter decomposition could not be demonstrated. Enrofloxacin significantly affected the structure of leaf-associated bacterial communities at the highest treatment level, and reduced the abundance of ammonia-oxidizing bacteria and ammonia-oxidizing archaea in the sediments, with calculated NOECs of 10 and <1 μg/L, respectively. The ammonia concentration in the microcosm water significantly increased in the highest treatment level, and nitrate production was decreased, indicating a potential impairment of the nitrification function at concentrations above 100 μg/L. The results of this study suggest that environmentally relevant concentrations of enrofloxacin are not likely to result in direct or indirect toxic effects on the invertebrate and primary producer communities, nor on important microbially mediated functions such as nitrification. Copyright © 2014 Elsevier B.V. All rights reserved.

Survey of ecotoxicologically-relevant reproductive endpoint coverage within the ECOTOX database across ToxCast ER agonists (SETAC)

EPA Science Inventory

Adipose tissue represents an important and understudied component of the endocrine system. Recent evidence suggests that endocrine-disrupting chemicals (EDCs) may be able to alter lipid development (e.g., adipogenesis) and/or the balance of lipid metabolism. The environmentally a...

Cumulative assessment of steroid receptor mediated activity of contaminants in water samples using in vitro bioassays. -EMGS

EPA Science Inventory

Cell-based in vitro assays show promise for water quality monitoring applications due to high sensitivity, the ability to quantitatively detect a biologically relevant effect endpoint such as receptor transactivation (i.e., effect-based monitoring), and the ability to assess comp...

Alternatives to in vivo tests to detect endocrine disrupting chemicals (EDCs) in fish and amphibians – interactions with estrogens, androgens, and thyroid hormones

EPA Science Inventory

Endocrine disruption is considered a highly relevant endpoint for environmental risk assessment of chemicals, plant protection products, biocides and pharmaceuticals. Therefore, screening for endocrine disruption – with focus on vertebrates (fish and amphibians) and estrogen, and...

In Silico Prediction of Toxicokinetic Parameters for Environmentally Relevant Chemicals with Application to Risk-Based Prioritization

EPA Science Inventory

Toxicokinetic (TK) models can help bridge the gap between chemical exposure and measured toxicity endpoints, thereby addressing an important component of chemical risk assessments. The fraction of a chemical unbound by plasma proteins (Fub) and metabolic clearance rate (CLint) ar...

Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

EPA Science Inventory

Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

Weighing the Evidence of Ecological Risk From Chemical Contamination in the Estuarine Environment Adjacent to the Portsmouth Naval Shipyard, Kittery, Maine, USA

DTIC Science & Technology

2001-05-30

for mussel growth and sea urchin toxicity were medium, we seasonal variations of AVS- SEM in sediments and the degree concluded medium weight of...and phaeopigments), toxicity to fertilization of sea iment (Table 3). Conversely, the measures used for the pelagic urchin (Arbacia punctulata...account for temporal and spatial variability. fidence level (C) for each assessment endpoint were assigned For toxicity to sea urchins , data quality

Using Flow-Ecology Relationships to Evaluate Ecosystem Service Trade-Offs and Complementarities in the Nation's Largest River Swamp.

PubMed

Kozak, Justin P; Bennett, Micah G; Hayden-Lesmeister, Anne; Fritz, Kelley A; Nickolotsky, Aaron

2015-06-01

Large river systems are inextricably linked with social systems; consequently, management decisions must be made within a given ecological, social, and political framework that often defies objective, technical resolution. Understanding flow-ecology relationships in rivers is necessary to assess potential impacts of management decisions, but translating complex flow-ecology relationships into stakeholder-relevant information remains a struggle. The concept of ecosystem services provides a bridge between flow-ecology relationships and stakeholder-relevant data. Flow-ecology relationships were used to explore complementary and trade-off relationships among 12 ecosystem services and related variables in the Atchafalaya River Basin, Louisiana. Results from Indicators of Hydrologic Alteration were reduced to four management-relevant hydrologic variables using principal components analysis. Multiple regression was used to determine flow-ecology relationships and Pearson correlation coefficients, along with regression results, were used to determine complementary and trade-off relationships among ecosystem services and related variables that were induced by flow. Seven ecosystem service variables had significant flow-ecology relationships for at least one hydrologic variable (R (2) = 0.19-0.64). River transportation and blue crab (Callinectes sapidus) landings exhibited a complementary relationship mediated by flow; whereas transportation and crawfish landings, crawfish landings and crappie (Pomoxis spp.) abundance, and blue crab landings and blue catfish (Ictalurus furcatus) abundance exhibited trade-off relationships. Other trade-off and complementary relationships among ecosystem services and related variables, however, were not related to flow. These results give insight into potential conflicts among stakeholders, can reduce the dimensions of management decisions, and provide initial hypotheses for experimental flow modifications.

Using Flow-Ecology Relationships to Evaluate Ecosystem Service Trade-Offs and Complementarities in the Nation's Largest River Swamp

NASA Astrophysics Data System (ADS)

Kozak, Justin P.; Bennett, Micah G.; Hayden-Lesmeister, Anne; Fritz, Kelley A.; Nickolotsky, Aaron

2015-06-01

Large river systems are inextricably linked with social systems; consequently, management decisions must be made within a given ecological, social, and political framework that often defies objective, technical resolution. Understanding flow-ecology relationships in rivers is necessary to assess potential impacts of management decisions, but translating complex flow-ecology relationships into stakeholder-relevant information remains a struggle. The concept of ecosystem services provides a bridge between flow-ecology relationships and stakeholder-relevant data. Flow-ecology relationships were used to explore complementary and trade-off relationships among 12 ecosystem services and related variables in the Atchafalaya River Basin, Louisiana. Results from Indicators of Hydrologic Alteration were reduced to four management-relevant hydrologic variables using principal components analysis. Multiple regression was used to determine flow-ecology relationships and Pearson correlation coefficients, along with regression results, were used to determine complementary and trade-off relationships among ecosystem services and related variables that were induced by flow. Seven ecosystem service variables had significant flow-ecology relationships for at least one hydrologic variable ( R 2 = 0.19-0.64). River transportation and blue crab ( Callinectes sapidus) landings exhibited a complementary relationship mediated by flow; whereas transportation and crawfish landings, crawfish landings and crappie ( Pomoxis spp.) abundance, and blue crab landings and blue catfish ( Ictalurus furcatus) abundance exhibited trade-off relationships. Other trade-off and complementary relationships among ecosystem services and related variables, however, were not related to flow. These results give insight into potential conflicts among stakeholders, can reduce the dimensions of management decisions, and provide initial hypotheses for experimental flow modifications.

The importance and pitfalls of correlational science in palliative care research.

PubMed

Klepstad, Pål; Kaasa, Stein

2012-12-01

Correlational science discovers associations between patient characteristics, symptoms and biomarkers. Correlational science using data from cross-sectional studies is the most frequently applied study design in palliative care research. The purpose of this review is to address the importance and potential pitfalls in correlational science. Associations observed in correlational science studies can be the basis for generating hypotheses that can be tested in experimental studies and are the basic data needed to develop classification systems that can predict patient outcomes. Major pitfalls in correlational science are that associations do not equate with causality and that statistical significance does not necessarily equal a correlation that is of clinical interest. Researchers should be aware of the end-points that are clinically relevant, that end-points should be defined before the start of the analyses, and that studies with several end-points should account for multiplicity. Correlational science in palliative care research can identify related clinical factors and biomarkers. Interpretation of identified associations should be done with careful consideration of the limitations underlying correlational analyses.

Disambiguating seesaw models using invariant mass variables at hadron colliders

NASA Astrophysics Data System (ADS)

Dev, P. S. Bhupal; Kim, Doojin; Mohapatra, Rabindra N.

2016-01-01

We propose ways to distinguish between different mechanisms behind the collider signals of TeV-scale seesaw models for neutrino masses using kinematic endpoints of invariant mass variables. We particularly focus on two classes of such models widely discussed in literature: (i) Standard Model extended by the addition of singlet neutrinos and (ii) Left-Right Symmetric Models. Relevant scenarios involving the same "smoking-gun" collider signature of dilepton plus dijet with no missing transverse energy differ from one another by their event topology, resulting in distinctive relationships among the kinematic endpoints to be used for discerning them at hadron colliders. These kinematic endpoints are readily translated to the mass parameters of the on-shell particles through simple analytic expressions which can be used for measuring the masses of the new particles. A Monte Carlo simulation with detector effects is conducted to test the viability of the proposed strategy in a realistic environment. Finally, we discuss the future prospects of testing these scenarios at the √{s}=14 and 100 TeV hadron colliders.

Prognostic factors versus markers of response to treatment versus surrogate endpoints: Three different concepts.

PubMed

Sormani, Maria Pia

2017-03-01

Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments.

Determinants for successful marketing authorisation of orphan medicinal products in the EU.

PubMed

Putzeist, Michelle; Heemstra, Harald E; Garcia, Jordi Llinares; Mantel-Teeuwisse, Aukje K; Gispen-De Wied, Christine C; Hoes, Arno W; Leufkens, Hubert G M

2012-04-01

In 2010, the European Regulation for Orphan Medicinal Products (OMPs) was in force for ten years. In this study we assessed possible determinants of applications for OMPs in the EU since 2000 that are associated with a successful marketing authorisation. Our analysis shows that clinical trial characteristics such as demonstrating convincing evidence of a beneficial effect on the primary endpoint, the selection of a clinically relevant endpoint, providing RCT data as pivotal study evidence and the submission of sound dose finding data are critical success factors. In addition, high medical need seems to counterweigh uncertainties about the scientific evidence in the benefit-risk assessment of OMPs. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dispersal constraints for stream invertebrates: setting realistic timescales for biodiversity restoration.

PubMed

Parkyn, Stephanie M; Smith, Brian J

2011-09-01

Biodiversity goals are becoming increasingly important in stream restoration. Typical models of stream restoration are based on the assumption that if habitat is restored then species will return and ecological processes will re-establish. However, a range of constraints at different scales can affect restoration success. Much of the research in stream restoration ecology has focused on habitat constraints, namely the in-stream and riparian conditions required to restore biota. Dispersal constraints are also integral to determining the timescales, trajectory and potential endpoints of a restored ecosystem. Dispersal is both a means of organism recolonization of restored sites and a vital ecological process that maintains viable populations. We review knowledge of dispersal pathways and explore the factors influencing stream invertebrate dispersal. From empirical and modeling studies of restoration in warm-temperate zones of New Zealand, we make predictions about the timescales of stream ecological restoration under differing levels of dispersal constraints. This process of constraints identification and timescale prediction is proposed as a practical step for resource managers to prioritize and appropriately monitor restoration sites and highlights that in some instances, natural recolonization and achievement of biodiversity goals may not occur.

Baseline ecological risk assessment of the Calcasieu Estuary, Louisiana: 1. Overview and problem formulation

USGS Publications Warehouse

MacDonald, Donald D.; Moore, Dwayne R.J.; Ingersoll, Christopher G.; Smorong, Dawn E.; Carr, R. Scott; Gouguet, Ron; Charters, David; Wilson, Duane; Harris, Tom; Rauscher, Jon; Roddy, Susan; Meyer, John

2011-01-01

A remedial investigation/feasibility study (RI/FS) of the Calcasieu Estuary cooperative site was initiated in 1998. This site, which is located in the southwestern portion of Louisiana in the vicinity of Lake Charles, includes the portion of the estuary from the saltwater barrier on the Calcasieu River to Moss Lake. As part of the RI/FS, a baseline ecological risk assessment (BERA) was conducted to assess the risks to aquatic organisms and aquatic-dependent wildlife exposed to environmental contaminants. The purpose of the BERA was to determine if adverse effects on ecological receptors are occurring in the estuary; to evaluate the nature, severity, and areal extent of any such effects; and to identify the substances that are causing or substantially contributing to effects on ecological receptors. This article describes the environmental setting and site history, identifies the chemicals of potential concern, presents the exposure scenarios and conceptual model for the site, and summarizes the assessment and measurement endpoints that were used in the investigation. Two additional articles in this series describe the results of an evaluation of effects-based sediment-quality guidelines as well as an assessment of risks to benthic invertebrates associated with exposure to contaminated sediment.

Advantages and limitations of quantitative PCR (Q-PCR)-based approaches in microbial ecology.

PubMed

Smith, Cindy J; Osborn, A Mark

2009-01-01

Quantitative PCR (Q-PCR or real-time PCR) approaches are now widely applied in microbial ecology to quantify the abundance and expression of taxonomic and functional gene markers within the environment. Q-PCR-based analyses combine 'traditional' end-point detection PCR with fluorescent detection technologies to record the accumulation of amplicons in 'real time' during each cycle of the PCR amplification. By detection of amplicons during the early exponential phase of the PCR, this enables the quantification of gene (or transcript) numbers when these are proportional to the starting template concentration. When Q-PCR is coupled with a preceding reverse transcription reaction, it can be used to quantify gene expression (RT-Q-PCR). This review firstly addresses the theoretical and practical implementation of Q-PCR and RT-Q-PCR protocols in microbial ecology, highlighting key experimental considerations. Secondly, we review the applications of (RT)-Q-PCR analyses in environmental microbiology and evaluate the contribution and advances gained from such approaches. Finally, we conclude by offering future perspectives on the application of (RT)-Q-PCR in furthering understanding in microbial ecology, in particular, when coupled with other molecular approaches and more traditional investigations of environmental systems.

Dispersal Constraints for Stream Invertebrates: Setting Realistic Timescales for Biodiversity Restoration

NASA Astrophysics Data System (ADS)

Parkyn, Stephanie M.; Smith, Brian J.

2011-09-01

Biodiversity goals are becoming increasingly important in stream restoration. Typical models of stream restoration are based on the assumption that if habitat is restored then species will return and ecological processes will re-establish. However, a range of constraints at different scales can affect restoration success. Much of the research in stream restoration ecology has focused on habitat constraints, namely the in-stream and riparian conditions required to restore biota. Dispersal constraints are also integral to determining the timescales, trajectory and potential endpoints of a restored ecosystem. Dispersal is both a means of organism recolonization of restored sites and a vital ecological process that maintains viable populations. We review knowledge of dispersal pathways and explore the factors influencing stream invertebrate dispersal. From empirical and modeling studies of restoration in warm-temperate zones of New Zealand, we make predictions about the timescales of stream ecological restoration under differing levels of dispersal constraints. This process of constraints identification and timescale prediction is proposed as a practical step for resource managers to prioritize and appropriately monitor restoration sites and highlights that in some instances, natural recolonization and achievement of biodiversity goals may not occur.

Warming increases chlorpyrifos effects on predator but not anti-predator behaviours.

PubMed

Dinh Van, Khuong; Janssens, Lizanne; Debecker, Sara; Stoks, Robby

2014-07-01

Recent insights indicate that negative effects of pesticides on aquatic biota occur at concentrations that current legislation considers environmentally protective. We here address two, potentially interacting, mechanisms that may contribute to the underestimation of the impact of sublethal pesticide effects in single species tests at room temperature: the impairment of predator and antipredator behaviours and the stronger impact of organophosphate pesticides at higher temperatures. To address these issues we assessed the effects of chlorpyrifos on the predator and antipredator behaviours of larvae of the damselfly Ischnura elegans, important intermediate predators in aquatic food webs, in a common-garden warming experiment with replicated low- and high-latitude populations along the latitudinal gradient of this species in Europe. Chlorpyrifos reduced the levels of predator behavioural endpoints, and this reduction was stronger at the higher temperature for head orientations and feeding strikes. Chlorpyrifos also impaired two key antipredator behavioural endpoints, activity reductions in response to predator cues were smaller in the presence of chlorpyrifos, and chlorpyrifos caused a lower escape swimming speed; these effects were independent of temperature. This suggests chlorpyrifos may impact food web interactions by changing predator-prey interactions both with higher (predators) and lower trophic levels (food). Given that only the interaction with the lower trophic level was more impaired at higher temperatures, the overall pesticide-induced changes in food web dynamics may be strongly temperature-dependent. These findings were consistent in damselflies from low- and high-latitude populations, illustrating that thermal adaptation will not mitigate the increased toxicity of pesticides at higher temperatures. Our study not only underscores the relevance of including temperature and prey-predator interactions in ecological risk assessment but also their potential interplay and thereby highlights the complexity of contaminant effects on predator-prey interactions being differentially temperature-dependent pending on the trophic level. Copyright © 2014 Elsevier B.V. All rights reserved.

Fear and loathing in the benthos: Responses of aquatic insect larvae to the pesticide imidacloprid in the presence of chemical signals of predation risk.

PubMed

Pestana, João L T; Loureiro, Susana; Baird, Donald J; Soares, Amadeu M V M

2009-06-28

The influence of interactions between pesticide exposure and perceived predation risk on the lethal and sub-lethal responses of two aquatic insects was investigated using the pesticide imidacloprid, and a combination of predator-release kairomones from trout and alarm substances from conspecifics. Laboratory experiments examined feeding and respiration rates of the caddisfly Sericostoma vittatum as well as the growth, emergence and respiration rates of the midge Chironomus riparius, exposed to sub-lethal concentrations of imidacloprid. The effects of the two stressors on burrowing behaviour of both species were also assessed. The results show significant effects of environmentally relevant concentrations of imidacloprid on all endpoints studied. Perceived predation risk also elicited sub-lethal effects in C. riparius and S. vittatum, the latter species being less responsive to predation cues. The effects of simultaneous exposure to both types of stressors were assessed using two different approaches: analysis of variance and conceptual models [concentration addition (CA) and independent action (IA)] normally used for the evaluation of contaminant mixture exposure. Both statistical approaches showed no significant interactions on responses in simultaneous exposures in the majority of parameters assessed with only a signification deviation from the reference CA and IA models being found for C. riparius respiration data contrary to the ANOVA results. Exposure to imidacloprid also compromised antipredator behavioural responses of both insect species, with potential negative consequences in terms of mortality from predation in the field. The results obtained demonstrate that natural and anthropogenic stressors can be treated within the same framework providing compatible data for modelling. For an improved interpretation of ecological effects it will be important to expand the mechanistic study of effects of combined exposure to pesticides and perceived predation risk by measuring different endpoints over a wider range of pesticide concentrations.

Environmental performances of Sardinian dairy sheep production systems at different input levels.

PubMed

Vagnoni, E; Franca, A; Breedveld, L; Porqueddu, C; Ferrara, R; Duce, P

2015-01-01

Although sheep milk production is a significant sector for the European Mediterranean countries, it shows serious competitiveness gaps. Minimizing the ecological impacts of dairy sheep farming systems could represent a key factor for farmers to bridging the gaps in competitiveness of such systems and also obtaining public incentives. However, scarce is the knowledge about the environmental performance of Mediterranean dairy sheep farms. The main objectives of this paper were (i) to compare the environmental impacts of sheep milk production from three dairy farms in Sardinia (Italy), characterized by different input levels, and (ii) to identify the hotspots for improving the environmental performances of each farm, by using a Life Cycle Assessment (LCA) approach. The LCA was conducted using two different assessment methods: Carbon Footprint-IPCC and ReCiPe end-point. The analysis, conducted "from cradle to gate", was based on the functional unit 1 kg of Fat and Protein Corrected Milk (FPCM). The observed trends of the environmental performances of the studied farming systems were similar for both evaluation methods. The GHG emissions revealed a little range of variation (from 2.0 to 2.3 kg CO2-eq per kg of FPCM) with differences between farming systems being not significant. The ReCiPe end-point analysis showed a larger range of values and environmental performances of the low-input farm were significantly different compared to the medium- and high-input farms. In general, enteric methane emissions, field operations, electricity and production of agricultural machineries were the most relevant processes in determining the overall environmental performances of farms. Future research will be dedicated to (i) explore and better define the environmental implications of the land use impact category in the Mediterranean sheep farming systems, and (ii) contribute to revising and improving the existing LCA dataset for Mediterranean farming systems. Copyright © 2014 Elsevier B.V. All rights reserved.

Validation of surrogate endpoints in advanced solid tumors: systematic review of statistical methods, results, and implications for policy makers.

PubMed

Ciani, Oriana; Davis, Sarah; Tappenden, Paul; Garside, Ruth; Stein, Ken; Cantrell, Anna; Saad, Everardo D; Buyse, Marc; Taylor, Rod S

2014-07-01

Licensing of, and coverage decisions on, new therapies should rely on evidence from patient-relevant endpoints such as overall survival (OS). Nevertheless, evidence from surrogate endpoints may also be useful, as it may not only expedite the regulatory approval of new therapies but also inform coverage decisions. It is, therefore, essential that candidate surrogate endpoints be properly validated. However, there is no consensus on statistical methods for such validation and on how the evidence thus derived should be applied by policy makers. We review current statistical approaches to surrogate-endpoint validation based on meta-analysis in various advanced-tumor settings. We assessed the suitability of two surrogates (progression-free survival [PFS] and time-to-progression [TTP]) using three current validation frameworks: Elston and Taylor's framework, the German Institute of Quality and Efficiency in Health Care's (IQWiG) framework and the Biomarker-Surrogacy Evaluation Schema (BSES3). A wide variety of statistical methods have been used to assess surrogacy. The strength of the association between the two surrogates and OS was generally low. The level of evidence (observation-level versus treatment-level) available varied considerably by cancer type, by evaluation tools and was not always consistent even within one specific cancer type. Not in all solid tumors the treatment-level association between PFS or TTP and OS has been investigated. According to IQWiG's framework, only PFS achieved acceptable evidence of surrogacy in metastatic colorectal and ovarian cancer treated with cytotoxic agents. Our study emphasizes the challenges of surrogate-endpoint validation and the importance of building consensus on the development of evaluation frameworks.

Modeling hard clinical end-point data in economic analyses.

PubMed

Kansal, Anuraag R; Zheng, Ying; Palencia, Roberto; Ruffolo, Antonio; Hass, Bastian; Sorensen, Sonja V

2013-11-01

The availability of hard clinical end-point data, such as that on cardiovascular (CV) events among patients with type 2 diabetes mellitus, is increasing, and as a result there is growing interest in using hard end-point data of this type in economic analyses. This study investigated published approaches for modeling hard end-points from clinical trials and evaluated their applicability in health economic models with different disease features. A review of cost-effectiveness models of interventions in clinically significant therapeutic areas (CV diseases, cancer, and chronic lower respiratory diseases) was conducted in PubMed and Embase using a defined search strategy. Only studies integrating hard end-point data from randomized clinical trials were considered. For each study included, clinical input characteristics and modeling approach were summarized and evaluated. A total of 33 articles (23 CV, eight cancer, two respiratory) were accepted for detailed analysis. Decision trees, Markov models, discrete event simulations, and hybrids were used. Event rates were incorporated either as constant rates, time-dependent risks, or risk equations based on patient characteristics. Risks dependent on time and/or patient characteristics were used where major event rates were >1%/year in models with fewer health states (<7). Models of infrequent events or with numerous health states generally preferred constant event rates. The detailed modeling information and terminology varied, sometimes requiring interpretation. Key considerations for cost-effectiveness models incorporating hard end-point data include the frequency and characteristics of the relevant clinical events and how the trial data is reported. When event risk is low, simplification of both the model structure and event rate modeling is recommended. When event risk is common, such as in high risk populations, more detailed modeling approaches, including individual simulations or explicitly time-dependent event rates, are more appropriate to accurately reflect the trial data.

Effects of pulp mill effluent on benthic assemblages in mesocosms along the Saint John River, Canada.

PubMed

Culp, Joseph M; Cash, Kevin J; Glozier, Nancy E; Brua, Robert B

2003-12-01

We used mesocosms to examine the impact of different concentrations of pulp mill effluent (PME) on structural and functional endpoints of a benthic assemblage in the Saint John River (NB, Canada) during 1999 and 2000. Previous studies on this effluent's effects produced conflicting results, with field surveys suggesting a pattern of mild nutrient enrichment, while laboratory toxicity tests linked effluent exposure to moderate contaminant effects. Experimental treatments included three concentrations of sulfite pulp mill effluent (0, 5, 10% v/v PME). Endpoints for the assessment included algal biomass and taxonomic composition, benthic invertebrate abundance and composition, and insect emergence. Low concentrations of PME increased periphyton biomass and caused changes in community structure within the diatom-dominated community. Pulp mill effluent addition had little effect on several structural endpoints measured for benthic invertebrates, including abundance and taxonomic richness, but significantly changed community composition. For both periphyton and benthic invertebrates, community composition endpoints were more sensitive indicators of PME exposure. Insect emergence was a highly relevant functional endpoint. When benthic and emerged insects were combined, total abundance increased with PME addition. Results from two trophic levels, which provided multiple lines of evidence, indicated that the main impact of these PME concentrations is nutrient enrichment rather than effluent toxicity. Our findings also suggest that benthic invertebrate and periphyton assemblages, algal biomass production, and insect emergence are sensitive response measures. Future studies may confirm this observation. The consideration of both functional and structural endpoints at different trophic levels can greatly improve our understanding the effects of discharges to rivers. Such an understanding could not have been obtained using standard assessment techniques and illustrates the value of mesocosms and the benthic community assemblage approach in environmental assessment.

Proof of concept demonstration of optimal composite MRI endpoints for clinical trials.

PubMed

Edland, Steven D; Ard, M Colin; Sridhar, Jaiashre; Cobia, Derin; Martersteck, Adam; Mesulam, M Marsel; Rogalski, Emily J

2016-09-01

Atrophy measures derived from structural MRI are promising outcome measures for early phase clinical trials, especially for rare diseases such as primary progressive aphasia (PPA), where the small available subject pool limits our ability to perform meaningfully powered trials with traditional cognitive and functional outcome measures. We investigated a composite atrophy index in 26 PPA participants with longitudinal MRIs separated by two years. Rogalski et al . [ Neurology 2014;83:1184-1191] previously demonstrated that atrophy of the left perisylvian temporal cortex (PSTC) is a highly sensitive measure of disease progression in this population and a promising endpoint for clinical trials. Using methods described by Ard et al . [ Pharmaceutical Statistics 2015;14:418-426], we constructed a composite atrophy index composed of a weighted sum of volumetric measures of 10 regions of interest within the left perisylvian cortex using weights that maximize signal-to-noise and minimize sample size required of trials using the resulting score. Sample size required to detect a fixed percentage slowing in atrophy in a two-year clinical trial with equal allocation of subjects across arms and 90% power was calculated for the PSTC and optimal composite surrogate biomarker endpoints. The optimal composite endpoint required 38% fewer subjects to detect the same percent slowing in atrophy than required by the left PSTC endpoint. Optimal composites can increase the power of clinical trials and increase the probability that smaller trials are informative, an observation especially relevant for PPA, but also for related neurodegenerative disorders including Alzheimer's disease.

Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints

PubMed Central

Thompson, John R; Spata, Enti; Abrams, Keith R

2015-01-01

We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta-analytical methods are implemented using illustrative examples in relapsing–remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions. PMID:26271918

Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints.

PubMed

Bujkiewicz, Sylwia; Thompson, John R; Spata, Enti; Abrams, Keith R

2017-10-01

We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta-analytical methods are implemented using illustrative examples in relapsing-remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions.

The Use of a Binary Composite Endpoint and Sample Size Requirement: Influence of Endpoints Overlap.

PubMed

Marsal, Josep-Ramon; Ferreira-González, Ignacio; Bertran, Sandra; Ribera, Aida; Permanyer-Miralda, Gaietà; García-Dorado, David; Gómez, Guadalupe

2017-05-01

Although composite endpoints (CE) are common in clinical trials, the impact of the relationship between the components of a binary CE on the sample size requirement (SSR) has not been addressed. We performed a computational study considering 2 treatments and a CE with 2 components: the relevant endpoint (RE) and the additional endpoint (AE). We assessed the strength of the components' interrelation by the degree of relative overlap between them, which was stratified into 5 groups. Within each stratum, SSR was computed for multiple scenarios by varying the events proportion and the effect of the therapy. A lower SSR using CE was defined as the best scenario for using the CE. In 25 of 66 scenarios the degree of relative overlap determined the benefit of using CE instead of the RE. Adding an AE with greater effect than the RE leads to lower SSR using the CE regardless of the AE proportion and the relative overlap. The influence of overlapping decreases when the effect on RE increases. Adding an AE with lower effect than the RE constitutes the most uncertain situation. In summary, the interrelationship between CE components, assessed by the relative overlap, can help to define the SSR in specific situations and it should be considered for SSR computation. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The great descriptor melting pot: mixing descriptors for the common good of QSAR models.

PubMed

Tseng, Yufeng J; Hopfinger, Anton J; Esposito, Emilio Xavier

2012-01-01

The usefulness and utility of QSAR modeling depends heavily on the ability to estimate the values of molecular descriptors relevant to the endpoints of interest followed by an optimized selection of descriptors to form the best QSAR models from a representative set of the endpoints of interest. The performance of a QSAR model is directly related to its molecular descriptors. QSAR modeling, specifically model construction and optimization, has benefited from its ability to borrow from other unrelated fields, yet the molecular descriptors that form QSAR models have remained basically unchanged in both form and preferred usage. There are many types of endpoints that require multiple classes of descriptors (descriptors that encode 1D through multi-dimensional, 4D and above, content) needed to most fully capture the molecular features and interactions that contribute to the endpoint. The advantages of QSAR models constructed from multiple, and different, descriptor classes have been demonstrated in the exploration of markedly different, and principally biological systems and endpoints. Multiple examples of such QSAR applications using different descriptor sets are described and that examined. The take-home-message is that a major part of the future of QSAR analysis, and its application to modeling biological potency, ADME-Tox properties, general use in virtual screening applications, as well as its expanding use into new fields for building QSPR models, lies in developing strategies that combine and use 1D through nD molecular descriptors.

Immunotoxicity and genotoxicity testing for in-flight experiments under microgravity

NASA Astrophysics Data System (ADS)

Hansen, Peter-Diedrich; Hansen, Peter-Diedrich; Unruh, Eckehardt

Life Sciences as Related to Space (F) Influence of Spaceflight Environment on Biological Systems (F44) Immunotoxicity and genotoxicity testing for In-flight experiments under microgravity Sensing approaches for ecosystem and human health Author: Peter D. Hansen Technische Universit¨t Berlin, Faculty VI - Planen, Bauen, Umwelt, a Institute for Ecological Research and Technology, Department for Ecotoxicology, Berlin, Germany Peter-diedrich.hansen@tu-berlin.de Eckehardt Unruh Technische Universit¨t Berlin, Faculty VI - Planen, Bauen, Umwelt, Institute a for Ecological Research and Technology, Department for Ecotoxicology, Berlin, Germany An immune response by mussel hemocytes is the selective reaction to particles which are identified as foreign by its immune system shown by phagocytosis. Phagocytotic activity is based on the chemotaxis and adhesion, ingestion and phagosome formation. The attachment at the surface of the hemocytes and consequently the uptake of the particles or bacteria can be directly quantified in the format of a fluorescent assay. Another relevant endpoint of phagocytosis is oxidative burst measured by luminescence. Phagocytosis-related production of ROS will be stimulated with opsonised zymosan. The hemocytes will be stored frozen at -80oC and reconstituted in-flight for the experiment. The assay system of the TRIPLELUX-B Experiment has been performed with a well-defined quantification and evaluation of the immune function phagocytosis. The indicator cells are the hemocytes of blue mussels (Mytilus edulis). The signals of the immuno cellular responses are translated into luminescence as a rapid optical reporter system. The results expected will determine whether the observed responses are caused by microgravity and/or radiation (change in permeability, endpoints in genotoxicity: DNA unwinding). The samples for genotoxicity will be processed after returning to earth. The immune system of invertebrates has not been studied so far in space. The choice of phagocytes from invertebrates is justified to study the universal validity of innate immune responses. The TRIPLELUX-B Experiment contributes to risk assessment concerning immunotoxicity under space flight conditions. The components of the phagocytosis test system for the BIOLAB are now established and the technical realization of the TRIPLELUX- B Experiment is in final progess. The components of the fully automated AEC (Advanced Experimental Containment) will be demonstrated in the poster. There will be two AECs for reference measurements at 1xg and 0xg. The AEC of the TRIPLELUX-B experiment will contribute to a real time operational monitoring for immunotoxicity testing on earth. The AEC will allow "real time monitoring" providing automated observations of immunotoxicity in coastal and inland waters.

Evaluation of neural reflex activation as a mode of action for the acute respiratory effects of ozone.

PubMed

Prueitt, Robyn L; Goodman, Julie E

2016-09-01

Exposure to elevated levels of ozone has been associated with a variety of respiratory-related health endpoints in both epidemiology and controlled human exposure studies, including lung function decrements and airway inflammation. A mode of action (MoA) for these effects has not been established, but it has been proposed that they may occur through ozone-induced activation of neural reflexes. We critically reviewed experimental studies of ozone exposure and neural reflex activation and applied the International Programme on Chemical Safety (IPCS) mode-of-action/human relevance framework to evaluate the biological plausibility and human relevance of this proposed MoA. Based on the currently available experimental data, we found that the proposed MoA of neural reflex activation is biologically plausible for the endpoint of ozone-induced lung function decrements at high ozone exposures, but further studies are needed to fill important data gaps regarding the relevance of this MoA at lower exposures. A role for the proposed MoA in ozone-induced airway inflammation is less plausible, as the evidence is conflicting and is also of unclear relevance given the lack of studies conducted at lower exposures. The evidence suggests a different MoA for ozone-induced inflammation that may still be linked to the key events in the proposed MoA, such that neural reflex activation may have some degree of involvement in modulating ozone-induced neutrophil influx, even if it is not a direct role.

Application of Adverse Outcome Pathways (AOPs) in Human ...

EPA Pesticide Factsheets

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

Acute and additive toxicity of ten photosystem-II herbicides to seagrass

NASA Astrophysics Data System (ADS)

Wilkinson, Adam D.; Collier, Catherine J.; Flores, Florita; Negri, Andrew P.

2015-11-01

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (ΔF/Fm‧) by 50% at concentrations ranging from 3.5 μg l-1 (ametryn) to 132 μg l-1 (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ΔF/Fm‧.

Application of adverse outcome pathways (AOPs) in human ...

EPA Pesticide Factsheets

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

Acute and additive toxicity of ten photosystem-II herbicides to seagrass

PubMed Central

Wilkinson, Adam D.; Collier, Catherine J.; Flores, Florita; Negri, Andrew P.

2015-01-01

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/Fm′) by 50% at concentrations ranging from 3.5 μg l−1 (ametryn) to 132 μg l−1 (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/Fm′. PMID:26616444

Acute and additive toxicity of ten photosystem-II herbicides to seagrass.

PubMed

Wilkinson, Adam D; Collier, Catherine J; Flores, Florita; Negri, Andrew P

2015-11-30

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/F(m)') by 50% at concentrations ranging from 3.5 μg l(-1) (ametryn) to 132 μg l(-1) (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/F(m)'.

Assessing cancer drugs for reimbursement: methodology, relationship between effect size and medical need.

PubMed

de Sahb-Berkovitch, Rima; Woronoff-Lemsi, Marie-Christine; Molimard, Mathieu

2010-01-01

Reimbursement is assessed by the Transparency Commission from the Health Authority (HAS) using a medical benefit (SMR) score that gives access to reimbursement, an "improvement of medical service rendered" (ASMR) that determines the added therapeutic value, and the target population. Assessing cancer drugs for reimbursement raises the same issues as other therapeutic classes, with some key differences. Overall survival (OS) is considered by the Transparency Commission as the endpoint for assessing clinical benefit, and yet it is not an applicable primary endpoint in all types of cancer. Later lines of treatment, particularly during the development process, may make it difficult to interpret OS as the primary endpoint. Therefore, progression-free survival (PFS) for metastatic situations and disease-free survival (DFS) in adjuvant situations are wholly relevant endpoints for decisions on the reimbursement of a new cancer drug. Effect size is assessed using actuarial survival curves of the product versus the comparator, and it is difficult to summarise them into one single parameter. Results are generally interpreted based on median survival, which is fragmented because it only measures one point of the curve. The hazard ratio measures the effect of treatment throughout the duration of survival and is therefore more comprehensive in quantifying clinical benefit. Determining an effect size threshold for granting reimbursement is difficult given the diversity of cancer settings and the level of medical need, which influences assessment of the clinical relevance of the observed difference. Rapid progress in comparators (700 molecules in development) and the identification of predictive factors of efficacy (biomarkers, histology, etc.) during development may lead to different ASMR scores per population, or to the restriction of the target population to a subgroup of the marketing authorisation (MA) population in which the expected effect size is greater. To address these issues, the roundtable recommends the possibility of early scientific opinions by the office of the Transparency Commission in order to discuss comparators and the relevance of responder subgroups. It also recommends the possibility of granting a temporary ASMR, on condition of subsequent confirmation by production of data, when reimbursement appears justified in a subpopulation of the MA for which only subgroup analysis is available. © 2010 Société Française de Pharmacologie et de Thérapeutique.

On the road to somewhere: Brain potentials reflect language effects on motion event perception.

PubMed

Flecken, Monique; Athanasopoulos, Panos; Kuipers, Jan Rouke; Thierry, Guillaume

2015-08-01

Recent studies have identified neural correlates of language effects on perception in static domains of experience such as colour and objects. The generalization of such effects to dynamic domains like motion events remains elusive. Here, we focus on grammatical differences between languages relevant for the description of motion events and their impact on visual scene perception. Two groups of native speakers of German or English were presented with animated videos featuring a dot travelling along a trajectory towards a geometrical shape (endpoint). English is a language with grammatical aspect in which attention is drawn to trajectory and endpoint of motion events equally. German, in contrast, is a non-aspect language which highlights endpoints. We tested the comparative perceptual saliency of trajectory and endpoint of motion events by presenting motion event animations (primes) followed by a picture symbolising the event (target): In 75% of trials, the animation was followed by a mismatching picture (both trajectory and endpoint were different); in 10% of trials, only the trajectory depicted in the picture matched the prime; in 10% of trials, only the endpoint matched the prime; and in 5% of trials both trajectory and endpoint were matching, which was the condition requiring a response from the participant. In Experiment 1 we recorded event-related brain potentials elicited by the picture in native speakers of German and native speakers of English. German participants exhibited a larger P3 wave in the endpoint match than the trajectory match condition, whereas English speakers showed no P3 amplitude difference between conditions. In Experiment 2 participants performed a behavioural motion matching task using the same stimuli as those used in Experiment 1. German and English participants did not differ in response times showing that motion event verbalisation cannot readily account for the difference in P3 amplitude found in the first experiment. We argue that, even in a non-verbal context, the grammatical properties of the native language and associated sentence-level patterns of event encoding influence motion event perception, such that attention is automatically drawn towards aspects highlighted by the grammar. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Scene Configuration and Object Reliability Affect the Use of Allocentric Information for Memory-Guided Reaching

PubMed Central

Klinghammer, Mathias; Blohm, Gunnar; Fiehler, Katja

2017-01-01

Previous research has shown that egocentric and allocentric information is used for coding target locations for memory-guided reaching movements. Especially, task-relevance determines the use of objects as allocentric cues. Here, we investigated the influence of scene configuration and object reliability as a function of task-relevance on allocentric coding for memory-guided reaching. For that purpose, we presented participants images of a naturalistic breakfast scene with five objects on a table and six objects in the background. Six of these objects served as potential reach-targets (= task-relevant objects). Participants explored the scene and after a short delay, a test scene appeared with one of the task-relevant objects missing, indicating the location of the reach target. After the test scene vanished, participants performed a memory-guided reaching movement toward the target location. Besides removing one object from the test scene, we also shifted the remaining task-relevant and/or task-irrelevant objects left- or rightwards either coherently in the same direction or incoherently in opposite directions. By varying object coherence, we manipulated the reliability of task-relevant and task-irrelevant objects in the scene. In order to examine the influence of scene configuration (distributed vs. grouped arrangement of task-relevant objects) on allocentric coding, we compared the present data with our previously published data set (Klinghammer et al., 2015). We found that reaching errors systematically deviated in the direction of object shifts, but only when the objects were task-relevant and their reliability was high. However, this effect was substantially reduced when task-relevant objects were distributed across the scene leading to a larger target-cue distance compared to a grouped configuration. No deviations of reach endpoints were observed in conditions with shifts of only task-irrelevant objects or with low object reliability irrespective of task-relevancy. Moreover, when solely task-relevant objects were shifted incoherently, the variability of reaching endpoints increased compared to coherent shifts of task-relevant objects. Our results suggest that the use of allocentric information for coding targets for memory-guided reaching depends on the scene configuration, in particular the average distance of the reach target to task-relevant objects, and the reliability of task-relevant allocentric information. PMID:28450826

Scene Configuration and Object Reliability Affect the Use of Allocentric Information for Memory-Guided Reaching.

PubMed

Klinghammer, Mathias; Blohm, Gunnar; Fiehler, Katja

2017-01-01

Previous research has shown that egocentric and allocentric information is used for coding target locations for memory-guided reaching movements. Especially, task-relevance determines the use of objects as allocentric cues. Here, we investigated the influence of scene configuration and object reliability as a function of task-relevance on allocentric coding for memory-guided reaching. For that purpose, we presented participants images of a naturalistic breakfast scene with five objects on a table and six objects in the background. Six of these objects served as potential reach-targets (= task-relevant objects). Participants explored the scene and after a short delay, a test scene appeared with one of the task-relevant objects missing, indicating the location of the reach target. After the test scene vanished, participants performed a memory-guided reaching movement toward the target location. Besides removing one object from the test scene, we also shifted the remaining task-relevant and/or task-irrelevant objects left- or rightwards either coherently in the same direction or incoherently in opposite directions. By varying object coherence, we manipulated the reliability of task-relevant and task-irrelevant objects in the scene. In order to examine the influence of scene configuration (distributed vs. grouped arrangement of task-relevant objects) on allocentric coding, we compared the present data with our previously published data set (Klinghammer et al., 2015). We found that reaching errors systematically deviated in the direction of object shifts, but only when the objects were task-relevant and their reliability was high. However, this effect was substantially reduced when task-relevant objects were distributed across the scene leading to a larger target-cue distance compared to a grouped configuration. No deviations of reach endpoints were observed in conditions with shifts of only task-irrelevant objects or with low object reliability irrespective of task-relevancy. Moreover, when solely task-relevant objects were shifted incoherently, the variability of reaching endpoints increased compared to coherent shifts of task-relevant objects. Our results suggest that the use of allocentric information for coding targets for memory-guided reaching depends on the scene configuration, in particular the average distance of the reach target to task-relevant objects, and the reliability of task-relevant allocentric information.

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

NASA Astrophysics Data System (ADS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

2004-01-01

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.

Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

PubMed

Healy, D A; Khan, W A; Wong, C S; Moloney, M Clarke; Grace, P A; Coffey, J C; Dunne, C; Walsh, S R; Sadat, U; Gaunt, M E; Chen, S; Tehrani, S; Hausenloy, D J; Yellon, D M; Kramer, R S; Zimmerman, R F; Lomivorotov, V V; Shmyrev, V A; Ponomarev, D N; Rahman, I A; Mascaro, J G; Bonser, R S; Jeon, Y; Hong, D M; Wagner, R; Thielmann, M; Heusch, G; Zacharowski, K; Meybohm, P; Bein, B; Tang, T Y

2014-09-01

A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Differences in end-point force trajectories elicited by electrical stimulation of individual human calf muscles

PubMed Central

Giordano, S B; Segal, R L; Abelew, T A

2009-01-01

The purpose of this study was to investigate the end-point force trajectories of the fibularis longus (FIB), lateral gastrocnemius (LG) and medial gastrocnemius (MG) muscles. Most information about individual muscle function has come from studies which use models based on electromyographic (EMG) recordings. In this study (N=20 subjects) we used electrical stimulation (20Hz) to elicit activity in individual muscles, recorded the end-point forces at the foot and verified the selectivity of stimulation by using magnetic resonance imaging. Unexpectedly, no significant differences were found between LG and MG force directions. Stimulation of LG and MG resulted in downward and medial or lateral forces depending on the subject. We found FIB end-point forces to be significantly different than those of LG and MG. In all subjects, stimulation of FIB resulted in downward and lateral forces. Based on our results, we suggest that there are multiple factors determining when and whether LG or MG will produce a medial or lateral force and FIB consistently plays a significant role in eversion/abduction and plantarflexion. We suggest that the inter-subject variability we found is not simply an artifact of experimental or technical error but is functionally relevant and should be addressed in future studies and models. PMID:20095454

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

NASA Technical Reports Server (NTRS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

2004-01-01

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

The Use of Surrogate and Patient-Relevant Endpoints in Outcomes-Based Market Access Agreements : Current Debate.

PubMed

Toumi, Mondher; Jarosławski, Szymon; Sawada, Toyohiro; Kornfeld, Åsa

2017-02-01

The high cost of novel treatments is the major driver of negative or restricted reimbursement decisions by healthcare payers in many countries. Costly drugs can be subject to Market Access Agreements (MAAs), which are financial (Commercial Agreements [CAs]) or outcomes-based (Payment for Performance Agreements [P4Ps] or Coverage with Evidence Development agreements [CEDs]). Outcomes in outcomes-based MAAs are assessed through changes in surrogate endpoints (SEPs) or patient-relevant endpoints (PEPs). In May 2015, we reviewed published and grey literature on MAAs between manufacturers and large, institutionalised payers from all geographical areas, and classified the schemes into CAs, P4Ps and CEDs, as well as by therapeutic area and country. Outcomes-based MAAs were further categorized by the endpoint used. Overall, we identified 143 MAAs, 56 (39.2 %) of which were pure CAs, 53 (37.1 %) were CEDs, and 34 (23.8 %) were P4Ps. Among the CEDs, 49 were PEP CEDs and four were SEP CEDs; of the 34 P4Ps, 29 were SEP P4Ps for 30 drugs, and five were PEP P4Ps for at least six drugs; and among 87 outcomes-based MAAs (CEDs + P4Ps), PEP CEDs were the most common (56.3 %), followed by SEP P4Ps (34.1 %). The high proportion of SEPs used in P4Ps contrasts with the high proportion of PEPs used in CEDs. CEDs employ PEPs and it appears that they are used to reduce uncertainty about a drug's clinical outcomes and/or real-life use, and thus allow payers to align a product's value with price. We argue that P4Ps do not reduce uncertainty about real-life effectiveness and can only constitute an outcome guarantee for payers if they are based on PEPs or validated SEPs.

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records.

PubMed

Pujades-Rodriguez, Mar; Guttmann, Oliver P; Gonzalez-Izquierdo, Arturo; Duyx, Bram; O'Mahony, Constantinos; Elliott, Perry; Hemingway, Harry

2018-01-01

To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997-2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67-43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69-10.85]), heart failure (4.31, [3.30-5.62]), and atrial fibrillation (3.80 [3.04-4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27-2.84]) and coronary revascularisation (2.32 [1.46-3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases.

Toxicological effects of fungicide mixtures on the amphipod Austrochiltonia subtenuis.

PubMed

Vu, Hung T; Keough, Michael J; Long, Sara M; Pettigrove, Vincent J

2017-10-01

Approaches to assess the toxicity of mixtures often use predictive models with acute mortality as an endpoint at relatively high concentrations. However, these approaches do not reflect realistic situations where organisms could be exposed to chemical mixtures over long periods at low concentrations at which no significant mortalities occur. The present study investigated chronic effects of 2 common fungicides, Filan® (active ingredient [a.i]) boscalid) and Systhane™ (a.i. myclobutanil), on the amphipod Austrochiltonia subtenuis at environmentally relevant concentrations under laboratory conditions. Sexually mature amphipods were exposed singly and in combination to Filan (1, 10, and 40 μg a.i./L) and Systhane (3 μg a.i./L) over 28 d. Survival, growth, a wide range of reproduction endpoints, and glutathione-S-transferase (GST) activity were measured at the end of the experiment. Both fungicides had significant independent effects on male growth, sex ratio, and juvenile size. Filan mainly affected female growth and the number of embryos per gravid female, whereas Systhane mainly affected the time for females to become gravid. The combined effects of these fungicides on numbers of gravid females and juveniles were antagonistic, causing a 61% reduction in the number of gravid females and a 77% reduction in the number of juveniles produced at the highest concentrations (40 μg a.i./L of boscalid and 3 μg a.i./L of myclobutanil) compared with the controls. There were no significant effects on survival or GST activity. The present study demonstrated that the effects of mixtures were endpoint dependent and that using a variety of endpoints should be considered for a comprehensive understanding of mixture effects. Also, chronic studies are more informative than acute studies for environmentally relevant fungicide concentrations. Environ Toxicol Chem 2017;36:2651-2659. © 2017 SETAC. © 2017 SETAC.

Building Ecology & School Design. Technical Bulletin.

ERIC Educational Resources Information Center

Maryland State Dept. of Education, Baltimore.

To better understand construction's impact, an overview of building ecology as a concept and as a decision-making model for school systems is provided. "Building ecology" is defined as the interrelationships among people, the built environment, and the natural environment. It has special relevance for school design because most of the…

The chemical ecology of cyanobacteria

PubMed Central

Leão, Pedro N.; Engene, Niclas; Antunes, Agostinho; Gerwick, William H.; Vasconcelos, Vitor

2014-01-01

This review covers the literature on the chemically mediated ecology of cyanobacteria, including ultraviolet radiation protection, feeding-deterrence, allelopathy, resource competition, and signalling. To highlight the chemical and biological diversity of this group of organisms, evolutionary and chemotaxonomical studies are presented. Several technologically relevant aspects of cyanobacterial chemical ecology are also discussed. PMID:22237837

Survey of ecotoxicologically-relevant reproductive endpoint coverage within the ECOTOX database across ToxCast ER agonists (ASCCT)

EPA Science Inventory

The U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) has been charged with screening thousands of chemicals for their potential to affect the endocrine systems of humans and wildlife. In vitro high throughput screening (HTS) assays have been proposed as a way to prioritize...

Applying adverse outcome pathways and species sensitivity-weighted distribution to predicted-no-effect concentration derivation and quantitative ecological risk assessment for bisphenol A and 4-nonylphenol in aquatic environments: A case study on Tianjin City, China.

PubMed

Wang, Ying; Na, Guangshui; Zong, Humin; Ma, Xindong; Yang, Xianhai; Mu, Jingli; Wang, Lijun; Lin, Zhongsheng; Zhang, Zhifeng; Wang, Juying; Zhao, Jinsong

2018-02-01

Adverse outcome pathways (AOPs) are a novel concept that effectively considers the toxic modes of action and guides the ecological risk assessment of chemicals. To better use toxicity data including biochemical or molecular responses and mechanistic data, we further developed a species sensitivity-weighted distribution (SSWD) method for bisphenol A and 4-nonylphenol. Their aquatic predicted-no-effect concentrations (PNECs) were derived using the log-normal statistical extrapolation method. We calculated aquatic PNECs of bisphenol A and 4-nonylphenol with values of 4.01 and 0.721 µg/L, respectively. The ecological risk of each chemical in different aquatic environments near Tianjin, China, a coastal municipality along the Bohai Sea, was characterized by hazard quotient and probabilistic risk quotient assessment techniques. Hazard quotients of 7.02 and 5.99 at 2 municipal sewage sites using all of the endpoints were observed for 4-nonylphenol, which indicated high ecological risks posed by 4-nonylphenol to aquatic organisms, especially endocrine-disrupting effects. Moreover, a high ecological risk of 4-nonylphenol was indicated based on the probabilistic risk quotient method. The present results show that combining the SSWD method and the AOP concept could better protect aquatic organisms from adverse effects such as endocrine disruption and could decrease uncertainty in ecological risk assessment. Environ Toxicol Chem 2018;37:551-562. © 2017 SETAC. © 2017 SETAC.

Characterization of transgenic mice--a comparison of protocols for welfare evaluation and phenotype characterization of mice with a suggestion on a future certificate of instruction.

PubMed

Jegstrup, I; Thon, R; Hansen, A K; Hoitinga, M Ritskes

2003-01-01

A thorough welfare evaluation performed as part of a general phenotype characterization for both transgenic and traditional mouse strains could not only contribute to the improvement of the welfare of laboratory animals, but could also be of benefit to scientists, laboratory veterinarians and the inspecting authorities. A literature review has been performed to identify and critically evaluate already existing protocols for phenotype and welfare characterization. There are several relevant schemes available, among others the SHIRPA method, the modified score sheet of Morton and Griffiths, the FRIMORFO phenotype characterization scheme and the behavioural phenotype schemes as described by Crawley. These protocols have been evaluated according to four goals: Their ability (1) to reveal any special needs or problems with a transgenic strain, (2) to cover the informational needs of the purchaser/user of the strain, (3) to refine the welfare of the transgenic animal model by identifying relevant humane endpoints, (4) to prevent the duplication of animal models that have already been developed. The protocols described are useful for characterizing the phenotype and judging welfare disturbances, however the total amount of information and the degree of detail varies considerably from one scheme to another. We present a proposal regarding the practical application of the various schemes that will secure proper treatment and the identification of humane endpoints. It is advocated that with every purchase of a particular strain, an instruction document should accompany the strain. This document needs to give detailed descriptions of the typical characteristics of the strain, as well as necessary actions concerning relevant treatment and humane endpoints. At the moment no such documents are required. The introduction of these types of documents will contribute to improvements in animal welfare as well as experimental results in laboratory animal experimentation.

EVALUATION GUIDELINES FOR ECOLOGICAL INDICATORS

EPA Science Inventory

This document presents fifteen technical guidelines to evaluate the suitability of an ecological indicator for a particular monitoring program. The guidelines are organized within four evaluation phrases: conceptual relevance, feasibility of implementation, response variability...

Genotoxicity of gemfibrozil in the gilthead seabream (Sparus aurata).

PubMed

Barreto, A; Luis, L G; Soares, A M V M; Paíga, P; Santos, L H M L M; Delerue-Matos, C; Hylland, K; Loureiro, S; Oliveira, M

2017-09-01

Widespread use of pharmaceuticals and suboptimal wastewater treatment have led to increased levels of these substances in aquatic ecosystems. Lipid-lowering drugs such as gemfibrozil, which are among the most abundant human pharmaceuticals in the environment, may have deleterious effects on aquatic organisms. We examined the genotoxicity of gemfibrozil in a fish species, the gilthead seabream (Sparus aurata), which is commercially important in southern Europe. Following 96-h waterborne exposure, molecular (erythrocyte DNA strand breaks) and cytogenetic (micronuclei and other nuclear abnormalities in cells) endpoints were measured. Gemfibrozil was positive in both endpoints, at environmentally relevant concentrations, a result that raises concerns about the potential genotoxic effects of the drug in recipient waters. Copyright © 2017 Elsevier B.V. All rights reserved.

An evolutionary ecology of individual differences

PubMed Central

Dall, Sasha R. X.; Bell, Alison M.; Bolnick, Daniel I.; Ratnieks, Francis L. W.

2014-01-01

Individuals often differ in what they do. This has been recognised since antiquity. Nevertheless, the ecological and evolutionary significance of such variation is attracting widespread interest, which is burgeoning to an extent that is fragmenting the literature. As a first attempt at synthesis, we focus on individual differences in behaviour within populations that exceed the day-to-day variation in individual behaviour (i.e. behavioural specialisation). Indeed, the factors promoting ecologically relevant behavioural specialisation within natural populations are likely to have far-reaching ecological and evolutionary consequences. We discuss such individual differences from three distinct perspectives: individual niche specialisations, the division of labour within insect societies and animal personality variation. In the process, while recognising that each area has its own unique motivations, we identify a number of opportunities for productive ‘crossfertilisation’ among the (largely independent) bodies of work. We conclude that a complete understanding of evolutionarily and ecologically relevant individual differences must specify how ecological interactions impact the basic biological process (e.g. Darwinian selection, development and information processing) that underpin the organismal features determining behavioural specialisations. Moreover, there is likely to be covariation amongst behavioural specialisations. Thus, we sketch the key elements of a general framework for studying the evolutionary ecology of individual differences. PMID:22897772

Role of Design in the Consumer Culture Development: Ecological Context

ERIC Educational Resources Information Center

Pankina, Marina V.; Khrustalyova, Christina ?.; Egarmin, Anton ?.; Shekhova, Natalia V.

2016-01-01

The relevance of the researched problem stems from ecological issues that are a reflection of the contemporary culture crisis covering the whole range of people's interactions with each other, with society and with nature. In many respects, an ecological crisis is an ideological crisis and global environmental problems are impossible to solve…

Spatial dependence of predictions from image segmentation: A variogram-based method to determine appropriate scales for producing land-management information

USDA-ARS?s Scientific Manuscript database

A significant challenge in ecological studies has been defining scales of observation that correspond to the relevant ecological scales for organisms or processes of interest. Remote sensing has become commonplace in ecological studies and management, but the default resolution of imagery often used...

Spatial dependence of predictions from image segmentation: a methods to determine appropriate scales for producing land-management information

USDA-ARS?s Scientific Manuscript database

A challenge in ecological studies is defining scales of observation that correspond to relevant ecological scales for organisms or processes. Image segmentation has been proposed as an alternative to pixel-based methods for scaling remotely-sensed data into ecologically-meaningful units. However, to...

Ecological periodic tables for benthic macrofaunal usage of estuarine habitats : Insights from a case study in Tillamook bay, Oregon, USA

EPA Science Inventory

This study validates the ecological relevance of estuarine habitat types to the benthic macrofaunal community and, together with previous similar studies, suggests they can serve as elements in ecological periodic tables of benthic macrofaunal usage in the bioregion. We compared...

Functional ecomorphology: Feedbacks between form and function in fluvial landscape ecosystems

NASA Astrophysics Data System (ADS)

Fisher, Stuart G.; Heffernan, James B.; Sponseller, Ryan A.; Welter, Jill R.

2007-09-01

The relationship between form and function has been a central organizing principle in biology throughout its history as a formal science. This concept has been relevant from molecules to organisms but loses meaning at population and community levels where study targets are abstract collectives and assemblages. Ecosystems include organisms and abiotic factors but ecosystem ecology too has developed until recently without a strong spatially explicit reference. Landscape ecology provides an opportunity to once again anneal form and function and to consider reciprocal causation between them. This ecomorphologic view can be applied at a variety of ecologically relevant scales and consists of an investigation of how geomorphology provides a structural template that shapes, and is shaped by ecological processes. Running water ecosystems illustrate several principles governing the interaction of landscape form and ecological function subsumed by the concept of "Functional Ecomorphology". Particularly lucrative are ecosystem-level interactions between geologic form and biogeochemical processes integrated by hydrologic flowpaths. While the utility of a flowpath-based approach is most apparent in streams, spatially explicit biogeochemical processing pervades all landscapes and may be of general ecological application.

Model independent particle mass measurements in missing energy events at hadron colliders

NASA Astrophysics Data System (ADS)

Park, Myeonghun

2011-12-01

This dissertation describes several new kinematic methods to measure the masses of new particles in events with missing transverse energy at hadron colliders. Each method relies on the measurement of some feature (a peak or an endpoint) in the distribution of a suitable kinematic variable. The first method makes use of the "Gator" variable s min , whose peak provides a global and fully inclusive measure of the production scale of the new particles. In the early stage of the LHC, this variable can be used both as an estimator and a discriminator for new physics over the standard model backgrounds. The next method studies the invariant mass distributions of the visible decay products from a cascade decay chain and the shapes and endpoints of those distributions. Given a sufficient number of endpoint measurements, one could in principle attempt to invert and solve for the mass spectrum. However, the non-linear character of the relevant coupled quadratic equations often leads to multiple solutions. In addition, there is a combinatorial ambiguity related to the ordering of the decay products from the cascade decay chain. We propose a new set of invariant mass variables which are less sensitive to these problems. We demonstrate how the new particle mass spectrum can be extracted from the measurement of their kinematic endpoints. The remaining methods described in the dissertation are based on "transverse" invariant mass variables like the "Cambridge" transverse mass MT2, the "Sheffield" contrasverse mass MCT and their corresponding one-dimensional projections MT2⊥, M T2||, MCT⊥ , and MCT|| with respect to the upstream transverse momentum U⃗T . The main advantage of all those methods is that they can be applied to very short (single-stage) decay topologies, as well as to a subsystem of the observed event. The methods can also be generalized to the case of non-identical missing particles, as demonstrated in Chapter 7. A complete set of analytical results for the calculation of the relevant variables in each event, as well as the dependence of their endpoints on the underlying mass spectrum is given for each case. In some circumstances, the whole shape of the differential distribution can be theoretically predicted as well. The methods are illustrated with examples from supersymmetry and from top quark production in the standard model.

Energy metabolism and biotransformation as endpoints to pre-screen hepatotoxicity using a liver spheroid model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Jinsheng; Purcell, Wendy M.

2006-10-15

The current study investigated liver spheroid culture as an in vitro model to evaluate the endpoints relevant to the status of energy metabolism and biotransformation after exposure to test toxicants. Mature rat liver spheroids were exposed to diclofenac, galactosamine, isoniazid, paracetamol, m-dinitrobenzene (m-DNB) and 3-nitroaniline (3-NA) for 24 h. Pyruvate uptake, galactose biotransformation, lactate release and glucose secretion were evaluated after exposure. The results showed that pyruvate uptake and lactate release by mature liver spheroids in culture were maintained at a relatively stable level. These endpoints, together with glucose secretion and galactose biotransformation, were related to and could reflect themore » status of energy metabolism and biotransformation in hepatocytes. After exposure, all of the test agents significantly reduced glucose secretion, which was shown to be the most sensitive endpoint of those evaluated. Diclofenac, isoniazid, paracetamol and galactosamine reduced lactate release (P < 0.01), but m-DNB increased lactate release (P < 0.01). Diclofenac, isoniazid and paracetamol also reduced pyruvate uptake (P < 0.01), while galactosamine had little discernible effect. Diclofenac, galactosamine, paracetamol and m-DNB also reduced galactose biotransformation (P < 0.01), by contrast, isoniazid did not. The metabolite of m-DNB, 3-NA, which served as a negative control, did not cause significant changes in lactate release, pyruvate uptake or galactose biotransformation. It is concluded that pyruvate uptake, galactose biotransformation, lactate release and glucose secretion can be used as endpoints for evaluating the status of energy metabolism and biotransformation after exposure to test agents using the liver spheroid model to pre-screen hepatotoxicity.« less

Earthworm Comet Assay for Assessing the Risk of Weathered Petroleum Hydrocarbon Contaminated Soils: Need to Look Further than Target Contaminants.

PubMed

Ramadass, Kavitha; Palanisami, Thavamani; Smith, Euan; Mayilswami, Srinithi; Megharaj, Mallavarapu; Naidu, Ravi

2016-11-01

Earthworm toxicity assays contribute to ecological risk assessment and consequently standard toxicological endpoints, such as mortality and reproduction, are regularly estimated. These endpoints are not enough to better understand the mechanism of toxic pollutants. We employed an additional endpoint in the earthworm Eisenia andrei to estimate the pollutant-induced stress. In this study, comet assay was used as an additional endpoint to evaluate the genotoxicity of weathered hydrocarbon contaminated soils containing 520 to 1450 mg hydrocarbons kg -1 soil. Results showed that significantly higher DNA damage levels (two to sixfold higher) in earthworms exposed to hydrocarbon impacted soils. Interestingly, hydrocarbons levels in the tested soils were well below site-specific screening guideline values. In order to explore the reasons for observed toxicity, the contaminated soils were leached with rainwater and subjected to earthworm tests, including the comet assay, which showed no DNA damage. Soluble hydrocarbon fractions were not found originally in the soils and hence no hydrocarbons leached out during soil leaching. The soil leachate's Electrical Conductivity (EC) decreased from an average of 1665 ± 147 to 204 ± 20 µS cm -1 . Decreased EC is due to the loss of sodium, magnesium, calcium, and sulphate. The leachate experiment demonstrated that elevated salinity might cause the toxicity and not the weathered hydrocarbons. Soil leaching removed the toxicity, which is substantiated by the comet assay and soil leachate analysis data. The implication is that earthworm comet assay can be included in future eco (geno) toxicology studies to assess accurately the risk of contaminated soils.

Advancing the integration of history and ecology for conservation.

PubMed

Szabó, Péter; Hédl, Radim

2011-08-01

The important role of humans in the development of current ecosystems was recognized decades ago; however, the integration of history and ecology in order to inform conservation has been difficult. We identified four issues that hinder historical ecological research and considered possible solutions. First, differences in concepts and methods between the fields of ecology and history are thought to be large. However, most differences stem from miscommunication between ecologists and historians and are less substantial than is usually assumed. Cooperation can be achieved by focusing on the features ecology and history have in common and through understanding and acceptance of differing points of view. Second, historical ecological research is often hampered by differences in spatial and temporal scales between ecology and history. We argue that historical ecological research can only be conducted at extents for which sources in both disciplines have comparable resolutions. Researchers must begin by clearly defining the relevant scales for the given purpose. Third, periods for which quantitative historical sources are not easily accessible (before AD 1800) have been neglected in historical ecological research. Because data from periods before 1800 are as relevant to the current state of ecosystems as more recent data, we suggest that historical ecologists actively seek out data from before 1800 and apply analytic methods commonly used in ecology to these data. Fourth, humans are not usually considered an intrinsic ecological factor in current ecological research. In our view, human societies should be acknowledged as integral parts of ecosystems and societal processes should be recognized as driving forces of ecosystem change. © 2011 Society for Conservation Biology.

Female reproductive impacts of dietary methylmercury in yellow perch (Perca flavescens) and zebrafish (Danio rerio).

PubMed

DeBofsky, Abigail R; Klingler, Rebekah H; Mora-Zamorano, Francisco X; Walz, Marcus; Shepherd, Brian; Larson, Jeremy K; Anderson, David; Yang, Luobin; Goetz, Frederick; Basu, Niladri; Head, Jessica; Tonellato, Peter; Armstrong, Brandon M; Murphy, Cheryl; Carvan, Michael J

2018-03-01

The purpose of this study was to evaluate the effects of environmentally relevant dietary MeHg exposures on adult female yellow perch (Perca flavescens) and female zebrafish (Danio rerio) ovarian development and reproduction. Yellow perch were used in the study for their socioeconomic and ecological importance within the Great Lakes basin, and the use of zebrafish allowed for a detailed analysis of the molecular effects of MeHg following a whole life-cycle exposure. Chronic whole life dietary exposure of F 1 zebrafish to MeHg mimics realistic wildlife exposure scenarios, and the twenty-week adult yellow perch exposure (where whole life-cycle exposures are difficult) captures early seasonal ovarian development. For both species, target dietary accumulation values were achieved prior to analyses. In zebrafish, several genes involved in reproductive processes were shown to be dysregulated by RNA-sequencing and quantitative real-time polymerase chain reaction (QPCR), but no significant phenotypic changes were observed regarding ovarian staging, fecundity, or embryo mortality. Yellow perch were exposed to dietary MeHg for 12, 16, or 20 weeks. In this species, a set of eight genes were assessed by QPCR in the pituitary, liver, and ovary, and no exposure-related changes were observed. The lack of genomic resources in yellow perch hinders the characterization of subtle molecular impacts. The ovarian somatic index, circulating estradiol and testosterone, and ovarian staging were not significantly altered by MeHg exposure in yellow perch. These results suggest that environmentally relevant MeHg exposures do not drastically reduce the reproductively important endpoints in these fish, but to capture realistic exposure scenarios, whole life-cycle yellow perch exposures are needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reflections on bird and mammal risk assessment for plant protection products in the European Union: Past, present, and future.

PubMed

Brooks, Amy C; Fryer, Mike; Lawrence, Alan; Pascual, Juan; Sharp, Rachel

2017-03-01

The use of plant protection products on agricultural crops can result in exposure of birds and mammals to toxic chemicals. In the European Union, the risks from such exposures are assessed under the current (2009) guidance document from the European Food Safety Authority (EFSA), designed to increase the realism of the theoretical risk assessments in comparison to its predecessor (SANCO/4145/2000). Since its adoption over 7 yr ago, many plant protection products have been evaluated successfully using the 2009 EFSA guidance document. However, there are still significant areas of improvement recommended for future revisions of this guidance. The present Focus article discusses experiences to date with the current scheme, including levels of conservatism in input parameters and interpretation by regulatory authorities together with proposals for how the guidance document could be improved when it is revised in the not too distant future. Several areas for which further guidance is recommended have been identified, such as the derivation of ecologically relevant bird and mammal reproductive endpoints and the use of modeling approaches to contextualize risk assessments. Areas where existing databases could be improved were also highlighted, including the collation of relevant focal species across Europe and expansion of the residue database for food items. To produce a realistic and useable guidance document in the future, it is strongly recommended that there is open and constructive communication between industry, regulatory authorities, and the EFSA. Such collaboration would also encourage harmonization between member states, thus reducing workloads for both industry and regulatory authorities. Environ Toxicol Chem 2017;36:565-575. © 2017 SETAC. © 2017 SETAC.

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures.

PubMed

Kunz, James L; Ingersoll, Chris G; Smalling, Kelly L; Elskus, Adria A; Kuivila, Kathryn M

2017-09-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubia and L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. azteca reproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;36:2308-2315. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2017 SETAC.

Novel Uses of In Vitro Data to Develop Quantitative Biological Activity Relationship Models for in Vivo Carcinogenicity Prediction.

PubMed

Pradeep, Prachi; Povinelli, Richard J; Merrill, Stephen J; Bozdag, Serdar; Sem, Daniel S

2015-04-01

The availability of large in vitro datasets enables better insight into the mode of action of chemicals and better identification of potential mechanism(s) of toxicity. Several studies have shown that not all in vitro assays can contribute as equal predictors of in vivo carcinogenicity for development of hybrid Quantitative Structure Activity Relationship (QSAR) models. We propose two novel approaches for the use of mechanistically relevant in vitro assay data in the identification of relevant biological descriptors and development of Quantitative Biological Activity Relationship (QBAR) models for carcinogenicity prediction. We demonstrate that in vitro assay data can be used to develop QBAR models for in vivo carcinogenicity prediction via two case studies corroborated with firm scientific rationale. The case studies demonstrate the similarities between QBAR and QSAR modeling in: (i) the selection of relevant descriptors to be used in the machine learning algorithm, and (ii) the development of a computational model that maps chemical or biological descriptors to a toxic endpoint. The results of both the case studies show: (i) improved accuracy and sensitivity which is especially desirable under regulatory requirements, and (ii) overall adherence with the OECD/REACH guidelines. Such mechanism based models can be used along with QSAR models for prediction of mechanistically complex toxic endpoints. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human adverse reproductive outcomes and electromagnetic field exposures: review of epidemiologic studies.

PubMed Central

Shaw, G M; Croen, L A

1993-01-01

Concerns have been raised regarding a relation between residential and occupational electromagnetic (EM) field exposures and adverse reproductive effects. This paper reviews the epidemiologic evidence for this possible relation, including some pertinent methodologic issues, notes relevant findings from the experimental literature, and discusses areas for future research. Evidence is lacking for a strong association between a woman's use of a video display terminal (VDT) during pregnancy and spontaneous abortion. The evidence for a strong association between a women's use of a VDT and other adverse reproductive endpoints is also lacking, with some suggestive findings for congenital malformations and too few data to reach a conclusion about other endpoints. With respect to low-level EM field exposures other than VDTs, the paucity of data prevents one from determining whether there are reproductive health risks associated with such exposures. Therefore, this is an area that needs further investigation. Given that altered growth may be an underlying biologic effect of EM field exposures, endpoints that might be pursued in future studies include congenital malformations not associated with chromosomal anomalies, intrauterine growth retardation, and chromosomally normal spontaneous abortions. PMID:8206019

Power/Sample Size Calculations for Assessing Correlates of Risk in Clinical Efficacy Trials

PubMed Central

Gilbert, Peter B.; Janes, Holly E.; Huang, Yunda

2016-01-01

In a randomized controlled clinical trial that assesses treatment efficacy, a common objective is to assess the association of a measured biomarker response endpoint with the primary study endpoint in the active treatment group, using a case-cohort, case-control, or two-phase sampling design. Methods for power and sample size calculations for such biomarker association analyses typically do not account for the level of treatment efficacy, precluding interpretation of the biomarker association results in terms of biomarker effect modification of treatment efficacy, with detriment that the power calculations may tacitly and inadvertently assume that the treatment harms some study participants. We develop power and sample size methods accounting for this issue, and the methods also account for inter-individual variability of the biomarker that is not biologically relevant (e.g., due to technical measurement error). We focus on a binary study endpoint and on a biomarker subject to measurement error that is normally distributed or categorical with two or three levels. We illustrate the methods with preventive HIV vaccine efficacy trials, and include an R package implementing the methods. PMID:27037797

Disambiguating seesaw models using invariant mass variables at hadron colliders

DOE PAGES

Dev, P. S. Bhupal; Kim, Doojin; Mohapatra, Rabindra N.

2016-01-19

Here, we propose ways to distinguish between different mechanisms behind the collider signals of TeV-scale seesaw models for neutrino masses using kinematic endpoints of invariant mass variables. We particularly focus on two classes of such models widely discussed in literature: (i) Standard Model extended by the addition of singlet neutrinos and (ii) Left-Right Symmetric Models. Relevant scenarios involving the same "smoking-gun" collider signature of dilepton plus dijet with no missing transverse energy differ from one another by their event topology, resulting in distinctive relationships among the kinematic endpoints to be used for discerning them at hadron colliders. Furthermore, these kinematic endpoints are readily translated to the mass parameters of the on-shell particles through simple analytic expressions which can be used for measuring the masses of the new particles. We also conducted a Monte Carlo simulation with detector effects in order to test the viability of the proposed strategy in a realistic environment. Finally, we discuss the future prospects of testing these scenarios at themore » $$\\sqrt{s}$$ = 14 and 100TeV hadron colliders.« less

Environmental security as related to scale mismatches of disturbance patterns in a panarchy of social-ecological landscapes

Treesearch

Giovanni Zurlini; Irene Petrosillo; Nicola Zaccarelli; Kurt Riitters

2008-01-01

Environmental security, as the opposite of environmental fragility (vulnerability), is multilayered, multi-scale and complex, existing in both the objective realm of biophysics and society, and the subjective realm of individual human perception. For ecological risk assessments (ERAs), the relevant objects of environmental security are social-ecological landscapes (...

Publications in anesthesia journals: quality and clinical relevance.

PubMed

Lauritsen, Jakob; Moller, Ann M

2004-11-01

Clinicians performing evidence-based anesthesia rely on anesthesia journals for clinically relevant information. The objective of this study was to analyze the proportion of clinically relevant articles in five high impact anesthesia journals. We evaluated all articles published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anesthesia, Anesthesia, and Acta Anaesthesiologica Scandinavica from January to June, 2000. Articles were assessed and classified according to type, outcome, and design; 1379 articles consisting of 5468 pages were evaluated and categorized. The most common types of article were animal and laboratory research (31.2%) and randomized clinical trial (20.4%). A clinically relevant article was defined as an article that used a statistically valid method and had a clinically relevant end-point. Altogether 18.6% of the pages had as their subject matter clinically relevant trials. We compared the Journal Impact Factor (a measure of the number of citations per article in a journal) and the proportion of clinically relevant pages and found that they were inversely proportional to each other.

The pros and cons of ecological risk assessment based on data from different levels of biological organization

PubMed Central

Rohr, Jason R.; Salice, Christopher J.; Nisbet, Roger M.

2016-01-01

Ecological risk assessment (ERA) is the process used to evaluate the safety of manufactured chemicals to the environment. Here we review the pros and cons of ERA across levels of biological organization, including suborganismal (e.g. biomarkers), individual, population, community, ecosystem, and landscapes levels. Our review revealed that level of biological organization is often related negatively with ease at assessing cause-effect relationships, ease of high-throughput screening of large numbers of chemicals (it is especially easier for suborganismal endpoints), and uncertainty of the ERA because low levels of biological organization tend to have a large distance between their measurement (what is quantified) and assessment endpoints (what is to be protected). In contrast, level of biological organization is often related positively with sensitivity to important negative and positive feedbacks and context dependencies within biological systems, and ease at capturing recovery from adverse contaminant effects. Some endpoints did not show obvious trends across levels of biological organization, such as the use of vertebrate animals in chemical testing and ease at screening large numbers of species, and other factors lacked sufficient data across levels of biological organization, such as repeatability, variability, cost per study, and cost per species of effects assessment, the latter of which might be a more defensible way to compare costs of ERAs than cost per study. To compensate for weaknesses of ERA at any particular level of biological organization, we also review mathematical modeling approaches commonly used to extrapolate effects across levels of organization. Finally, we provide recommendations for next generation ERA, submitting that if there is an ideal level of biological organization to conduct ERA, it will only emerge if ERA is approached simultaneously from the bottom of biological organization up as well as from the top down, all while employing mathematical modeling approaches where possible to enhance ERA. Because top-down ERA is unconventional, we also offer some suggestions for how it might be implemented efficaciously. We hope this review helps researchers in the field of ERA fill key information gaps and helps risk assessors identify the best levels of biological organization to conduct ERAs with differing goals. PMID:27340745

Frequent and seasonally variable sublethal anthrax infections are accompanied by short-lived immunity in an endemic system

PubMed Central

Cizauskas, Carrie A.; Bellan, Steven E.; Turner, Wendy C.; Vance, Russell E.; Getz, Wayne M.

2014-01-01

Summary Few studies have examined host-pathogen interactions in wildlife from an immunological perspective, particularly in the context of seasonal and longitudinal dynamics. In addition, though most ecological immunology studies employ serological antibody assays, endpoint titer determination is usually based on subjective criteria and needs to be made more objective. Despite the fact that anthrax is an ancient and emerging zoonotic infectious disease found worldwide, its natural ecology is not well understood. In particular, little is known about the adaptive immune responses of wild herbivore hosts against Bacillus anthracis. Working in the natural anthrax system of Etosha National Park, Namibia, we collected 154 serum samples from plains zebra (Equus quagga), 21 from springbok (Antidorcas marsupialis), and 45 from African elephants (Loxodonta africana) over 2-3 years, resampling individuals when possible for seasonal and longitudinal comparisons. We used enzyme-linked immunosorbent assays to measure anti-anthrax antibody titers and developed three increasingly conservative models to determine endpoint titers with more rigorous, objective mensuration. Between 52-87% of zebra, 0-15% of springbok, and 3-52% of elephants had measurable anti-anthrax antibody titers, depending on the model used. While the ability of elephants and springbok to mount anti-anthrax adaptive immune responses is still equivocal, our results indicate that zebra in ENP often survive sublethal anthrax infections, encounter most B. anthracis in the wet season, and can partially booster their immunity to B. anthracis. Thus, rather than being solely a lethal disease, anthrax often occurs as a sublethal infection in some susceptible hosts. Though we found that adaptive immunity to anthrax wanes rapidly, subsequent and frequent sublethal B. anthracis infections cause maturation of anti-anthrax immunity. By triggering host immune responses, these common sublethal infections may act as immunomodulators and affect population dynamics through indirect immunological and co-infection effects. In addition, with our three endpoint titer models, we introduce more mensuration rigor into serological antibody assays, even under the often-restrictive conditions that come with adapting laboratory immunology methods to wild systems. With these methods we identified significantly more zebras responding immunologically to anthrax than have previous studies using less comprehensive titer analyses. PMID:24499424

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose- response curves and recovery of function

NASA Astrophysics Data System (ADS)

Rabin, B.; Joseph, J.; Shukitt-Hale, B.

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation- induced disruption of dopaminergic function disrupts a variety of behaviors that are dependent upon the integrity of the dopaminergic system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, spatial learning and memory (Morris water maze), and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current presentation will review the data relevant to the degree to which these characteristics are in fact common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. Supported by N.A.S.A. Grant NAG9-1190.

Exploring possible mechanisms of action for the nanotoxicity and protein binding of decorated nanotubes: interpretation of physicochemical properties from optimal QSAR models.

PubMed

Esposito, Emilio Xavier; Hopfinger, Anton J; Shao, Chi-Yu; Su, Bo-Han; Chen, Sing-Zuo; Tseng, Yufeng Jane

2015-10-01

Carbon nanotubes have become widely used in a variety of applications including biosensors and drug carriers. Therefore, the issue of carbon nanotube toxicity is increasingly an area of focus and concern. While previous studies have focused on the gross mechanisms of action relating to nanomaterials interacting with biological entities, this study proposes detailed mechanisms of action, relating to nanotoxicity, for a series of decorated (functionalized) carbon nanotube complexes based on previously reported QSAR models. Possible mechanisms of nanotoxicity for six endpoints (bovine serum albumin, carbonic anhydrase, chymotrypsin, hemoglobin along with cell viability and nitrogen oxide production) have been extracted from the corresponding optimized QSAR models. The molecular features relevant to each of the endpoint respective mechanism of action for the decorated nanotubes are also discussed. Based on the molecular information contained within the optimal QSAR models for each nanotoxicity endpoint, either the decorator attached to the nanotube is directly responsible for the expression of a particular activity, irrespective of the decorator's 3D-geometry and independent of the nanotube, or those decorators having structures that place the functional groups of the decorators as far as possible from the nanotube surface most strongly influence the biological activity. These molecular descriptors are further used to hypothesize specific interactions involved in the expression of each of the six biological endpoints. Copyright © 2015 Elsevier Inc. All rights reserved.

Linking Aquatic Ecosystems to Human Well-Being

EPA Science Inventory

While ecological indicators should have relevance to people, a clear methodology to develop and evaluate this characteristic of ecological indicators is not well developed. Economists developed the concept of “Final Ecosystem Goods and Services”. Because these featur...

A regional-scale ecological risk framework for environmental flow evaluations

NASA Astrophysics Data System (ADS)

O'Brien, Gordon C.; Dickens, Chris; Hines, Eleanor; Wepener, Victor; Stassen, Retha; Quayle, Leo; Fouchy, Kelly; MacKenzie, James; Graham, P. Mark; Landis, Wayne G.

2018-02-01

Environmental flow (E-flow) frameworks advocate holistic, regional-scale, probabilistic E-flow assessments that consider flow and non-flow drivers of change in a socio-ecological context as best practice. Regional-scale ecological risk assessments of multiple stressors to social and ecological endpoints, which address ecosystem dynamism, have been undertaken internationally at different spatial scales using the relative-risk model since the mid-1990s. With the recent incorporation of Bayesian belief networks into the relative-risk model, a robust regional-scale ecological risk assessment approach is available that can contribute to achieving the best practice recommendations of E-flow frameworks. PROBFLO is a holistic E-flow assessment method that incorporates the relative-risk model and Bayesian belief networks (BN-RRM) into a transparent probabilistic modelling tool that addresses uncertainty explicitly. PROBFLO has been developed to evaluate the socio-ecological consequences of historical, current and future water resource use scenarios and generate E-flow requirements on regional spatial scales. The approach has been implemented in two regional-scale case studies in Africa where its flexibility and functionality has been demonstrated. In both case studies the evidence-based outcomes facilitated informed environmental management decision making, with trade-off considerations in the context of social and ecological aspirations. This paper presents the PROBFLO approach as applied to the Senqu River catchment in Lesotho and further developments and application in the Mara River catchment in Kenya and Tanzania. The 10 BN-RRM procedural steps incorporated in PROBFLO are demonstrated with examples from both case studies. PROBFLO can contribute to the adaptive management of water resources and contribute to the allocation of resources for sustainable use of resources and address protection requirements.

Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium†

PubMed Central

Leon, Martin B.; Piazza, Nicolo; Nikolsky, Eugenia; Blackstone, Eugene H.; Cutlip, Donald E.; Kappetein, Arie Pieter; Krucoff, Mitchell W.; Mack, Michael; Mehran, Roxana; Miller, Craig; Morel, Marie-angèle; Petersen, John; Popma, Jeffrey J.; Takkenberg, Johanna J.M.; Vahanian, Alec; van Es, Gerrit-Anne; Vranckx, Pascal; Webb, John G.; Windecker, Stephan; Serruys, Patrick W.

2011-01-01

Objectives To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health. Background Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials. Methods and results The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the US Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended. Conclusion Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes. PMID:21216739

Environmental risk assessment of pharmaceutical drug substances--conceptual considerations.

PubMed

Länge, Reinhard; Dietrich, Daniel

2002-05-10

Drugs, i.e. active ingredients of human medicinal products, may be introduced into the environment after use in patients by sewage effluent pathways and consequently are detected at low concentrations in sewage effluents and in surface waters. Legal requirements in a number of geographical regions (Europe, US, and intended in Canada) demand environmental risk assessments (ERA) for new drug substances. Existing regulatory concepts of ERA are based initially on a set of short-term ecotoxicological studies in three to four different species, environmental behavior and the application of assessment factors to correct for the ERA inherent uncertainty. Based on theoretical considerations and the experience with a very limited, but well investigated, number of examples while considering that drugs are highly biologically active compounds, the appropriateness of this risk assessment procedure for all drug substances might be questioned. Indeed, e.g. long-term effects may occur at much lower concentrations and follow different toxicodynamic mechanism than extrapolated from short-term studies., In such cases, the application of assessment factors for deriving chronic no-observed effect concentration (NOECs) appears to be problematic. Although long-term tests with a variety of organisms would provide a complete database for the evaluation of the environmental risks, this is unachievable for all drugs due to time, money and animal welfare constraints. In order to avoid unnecessary testing, a concept is presented, which makes use of pharmacological and toxicological, as well as pharmaco- and toxicokinetic information derived from mammals during drug substance development. Useful data for adoption in a case-by-case testing strategy can be obtained by evaluating (a) the pharmacological activity, which indicates specific targets in mammalian species and may allow for an analysis, whether a similar target is available in aquatic species; (b) the mammalian toxicity, which may indicate, which targets are most susceptible to adverse effects; (c) the difference between acute and chronic effects in mammals, since the magnitude of this difference may indicate, whether long-term effects are expected at significantly lower levels than acute effects; (d) the (pharmacologically and toxicologically) effective plasma levels in mammalian test organisms, which may be compared with the relevant exposure scenario for the environment. Additionally, activity classes of compounds may be established based on experience with specific substances, in order to develop an appropriate test strategy. The above preliminary considerations should support decisions on the selection of candidate substances for chronic effects studies and for the appropriate selection of test species and endpoints to monitor. Generally, ecologically relevant endpoints such as impairment of growth, development and reproduction should be used to assess the ecotoxicologic effects.

C-terminal provasopressin (copeptin) is a strong prognostic marker in patients with heart failure after an acute myocardial infarction: results from the OPTIMAAL study.

PubMed

Voors, Adriaan A; von Haehling, Stephan; Anker, Stefan D; Hillege, Hans L; Struck, Joachim; Hartmann, Oliver; Bergmann, Andreas; Squire, Iain; van Veldhuisen, Dirk J; Dickstein, Kenneth

2009-05-01

The aim of the present study was to compare the prognostic value of a novel and promising marker, copeptin, with B-type natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP), on death or a composite cardiovascular endpoint in patients who developed heart failure after an acute myocardial infarction (AMI). From a subset of 224 patients of the OPTIMAAL study, blood samples were drawn at a mean of 3 days after AMI when all patients had signs and/or symptoms of heart failure or a left ventricular ejection fraction <0.35. Endpoints of interest were mortality (primary endpoint of OPTIMAAL) and a composite cardiovascular endpoint, including death, MI, stroke, and/or resuscitated cardiac arrest. Mean age was 67 +/- 10 years, and mean follow-up was 33 +/- 7 months. Using univariable Cox proportional hazards survival analysis, higher levels of copeptin, BNP, and NT-proBNP were all significantly related to both mortality and the composite cardiovascular endpoint (all P < 0.01). In a multivariable Cox proportional hazards model, including all three biomarkers and other relevant covariates, a doubling of copeptin was related to a 1.83 (1.26-2.64) times increased risk of mortality (P < 0.0001) and a 1.35 (1.05-1.72) times increased risk of the composite cardiovascular endpoint (P = 0.018). Receiver operating characteristic curves indicated that copeptin [area under curve (AUC) 0.81] was a stronger predictor of mortality compared with both BNP (AUC 0.66; P = 0.0063 vs. copeptin) and NT-proBNP (AUC 0.67; P = 0.0016 vs. copeptin). Finally, changes of copeptin levels after 1 month significantly added prognostic information to the baseline value. Copeptin is a strong and novel marker for mortality and morbidity in patients with heart failure after AMI. In this population, the predictive value of copeptin was even stronger than BNP and NT-proBNP.

Approving cancer treatments based on endpoints other than overall survival: an analysis of historical data using the PACE Continuous Innovation Indicators™ (CII).

PubMed

Brooks, Neon; Campone, Mario; Paddock, Silvia; Shortenhaus, Scott; Grainger, David; Zummo, Jacqueline; Thomas, Samuel; Li, Rose

2017-01-01

There is an active debate about the role that endpoints other than overall survival (OS) should play in the drug approval process. Yet the term 'surrogate endpoint' implies that OS is the only critical metric for regulatory approval of cancer treatments. We systematically analyzed the relationship between U.S. Food and Drug Administration (FDA) approval and publication of OS evidence to understand better the risks and benefits of delaying approval until OS evidence is available. Using the PACE Continuous Innovation Indicators (CII) platform, we analyzed the effects of cancer type, treatment goal, and year of approval on the lag time between FDA approval and publication of first significant OS finding for 53 treatments approved between 1952 and 2016 for 10 cancer types (n = 71 approved indications). Greater than 59% of treatments were approved before significant OS data for the approved indication were published. Of the drugs in the sample, 31% had lags between approval and first published OS evidence of 4 years or longer. The average number of years between approval and first OS evidence varied by cancer type and did not reliably predict the eventual amount of OS evidence accumulated. Striking the right balance between early access and minimizing risk is a central challenge for regulators worldwide. We illustrate that endpoints other than OS have long helped to provide timely access to new medicines, including many current standards of care. We found that many critical drugs are approved many years before OS data are published, and that OS may not be the most appropriate endpoint in some treatment contexts. Our examination of approved treatments without significant OS data suggests contexts where OS may not be the most relevant endpoint and highlights the importance of using a wide variety of fit-for-purpose evidence types in the approval process.

Risk prediction in stable cardiovascular disease using a high-sensitivity cardiac troponin T single biomarker strategy compared to the ESC-SCORE.

PubMed

Biener, Moritz; Giannitsis, Evangelos; Kuhner, Manuel; Zelniker, Thomas; Mueller-Hennessen, Matthias; Vafaie, Mehrshad; Stoyanov, Kiril M; Neumann, Franz-Josef; Katus, Hugo A; Hochholzer, Willibald; Valina, Christian Marc

2018-01-01

To evaluate the prognostic performance of high-sensitivity cardiac troponin T (hs-cTnT) compared with the ESC-SCORE. We included low-risk outpatients with stable cardiovascular (CV) disease categorised into need for non-secondary and secondary prevention. The prognostication of hs-cTnT at index visit was compared with the European Society of Cardiology-Systematic COronary Risk Evaluation (ESC-SCORE) with respect to all-cause mortality (ACM) and two composite endpoints (ACM, acute myocardial infarction (AMI) and stroke and ACM, AMI, stroke and rehospitalisation for acute coronary syndrome (ACS) and decompensated heart failure (DHF)). Within a median follow-up of 796 days, a total of 16 deaths, 32 composite endpoints of ACM, AMI and stroke and 83 composite endpoints of ACM, AMI, stroke, rehospitalisation for ACS and DHF were observed among 693 stable low-risk outpatients. Using C-statistics, measurement of hs-cTnT alone outperformed the ESC-SCORE for the prediction of ACM in the entire study population (Δarea under the curve (AUC) 0.221, p=0.0039) and both prevention groups (non-secondary: ΔAUC 0.164, p=0.0208; secondary: ΔAUC 0.264, p=0.0134). For the prediction of all other secondary endpoints, hs-cTnT was at least as effective as the ESC-SCORE, both in secondary and non-secondary prevention. Using continuous and categorical net reclassification improvement and integrated discrimination improvement, hs-cTnT significantly improved reclassification regarding all endpoints in the entire population and in the secondary prevention cohort. In non-secondary prevention, hs-cTnT improved reclassification only for ACM. The results were confirmed in an independent external cohort on 2046 patients. Hs-cTnT is superior to the multivariable ESC-SCORE for the prediction of ACM and a composite endpoint in stable outpatients with and without relevant CV disease. NCT01954303; Pre-results.

Alternative Endpoints and Approaches Selected for the Remediation of Contaminated Groundwater at Complex Sites

NASA Astrophysics Data System (ADS)

Deeb, R. A.; Hawley, E.

2011-12-01

This presentation will focus on findings, statistics, and case studies from a recently-completed report for the Department of Defense's Environmental Security Technology Certification Program (ESTCP) (Project ER-0832) on alternative endpoints and alternative remedial strategies for groundwater remediation under a variety of Federal and state cleanup programs, including technical impracticability (TI) and other Applicable or Relevant and Appropriate Requirement (ARAR) waivers, state and local designations such as groundwater management zones, Alternate Concentration Limits (ACLs), use of monitored natural attenuation (MNA) over long timeframes, and more. The primary objective of the project was to provide environmental managers and regulators with tools, metrics, and information needed to evaluate alternative endpoints for groundwater remediation at complex sites. A statistical analysis of Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) sites receiving TI waivers will be presented as well as case studies of other types of alternative endpoints and alternative remedial strategies to illustrate the variety of approaches used at complex sites and the technical analyses used to predict and document cost, timeframe, and potential remedial effectiveness. Case studies provide examples of the flexible, site-specific, application of alternative endpoints and alternative remedial strategies that have been used in the past to manage and remediate groundwater contamination at complex sites. For example, at least 13 states consider some designation for groundwater containment in their corrective action policies, such as groundwater management zones, containment zones, and groundwater classification exemption areas. These designations typically indicate that groundwater contamination is present above permissible levels. Soil and groundwater within these zones are managed to protect human health and the environment. Lesson learned for the analyses conducted and the case studies evaluated allow for a more careful consideration of alternative, beneficial, and cost-effective cleanup objectives and metrics that can be achieved over the short-term (while eventually meeting long-term cleanup objectives or demonstrating the applicability of alternative endpoints), thus improving the site cleanup process at complex sites where appropriate.

Music therapy for people with schizophrenia and schizophrenia-like disorders.

PubMed

Mössler, Karin; Chen, Xijing; Heldal, Tor Olav; Gold, Christian

2011-12-07

Music therapy is a therapeutic method that uses musical interaction as a means of communication and expression. The aim of the therapy is to help people with serious mental disorders to develop relationships and to address issues they may not be able to using words alone. To review the effects of music therapy, or music therapy added to standard care, compared with 'placebo' therapy, standard care or no treatment for people with serious mental disorders such as schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (December 2010) and supplemented this by contacting relevant study authors, handsearching of music therapy journals and manual searches of reference lists. All randomised controlled trials (RCTs) that compared music therapy with standard care, placebo therapy, or no treatment. Studies were reliably selected, quality assessed and data extracted. We excluded data where more than 30% of participants in any group were lost to follow-up. We synthesised non-skewed continuous endpoint data from valid scales using a standardised mean difference (SMD). If statistical heterogeneity was found, we examined treatment 'dosage' and treatment approach as possible sources of heterogeneity. We included eight studies (total 483 participants). These examined effects of music therapy over the short- to medium-term (one to four months), with treatment 'dosage' varying from seven to 78 sessions. Music therapy added to standard care was superior to standard care for global state (medium-term, 1 RCT, n = 72, RR 0.10 95% CI 0.03 to 0.31, NNT 2 95% CI 1.2 to 2.2). Continuous data identified good effects on negative symptoms (4 RCTs, n = 240, SMD average endpoint Scale for the Assessment of Negative Symptoms (SANS) -0.74 95% CI -1.00 to -0.47); general mental state (1 RCT, n = 69, SMD average endpoint Positive and Negative Symptoms Scale (PANSS) -0.36 95% CI -0.85 to 0.12; 2 RCTs, n=100, SMD average endpoint Brief Psychiatric Rating Scale (BPRS) -0.73 95% CI -1.16 to -0.31); depression (2 RCTs, n = 90, SMD average endpoint Self-Rating Depression Scale (SDS) -0.63 95% CI -1.06 to -0.21; 1 RCT, n = 30, SMD average endpoint Hamilton Depression Scale (Ham-D) -0.52 95% CI -1.25 to -0.21 ); and anxiety (1 RCT, n = 60, SMD average endpoint SAS -0.61 95% CI -1.13 to -0.09). Positive effects were also found for social functioning (1 RCT, n = 70, SMD average endpoint Social Disability Schedule for Inpatients (SDSI) score -0.78 95% CI -1.27 to -0.28). Furthermore, some aspects of cognitive functioning and behaviour seem to develop positively through music therapy. Effects, however, were inconsistent across studies and depended on the number of music therapy sessions as well as the quality of the music therapy provided. Music therapy as an addition to standard care helps people with schizophrenia to improve their global state, mental state (including negative symptoms) and social functioning if a sufficient number of music therapy sessions are provided by qualified music therapists. Further research should especially address the long-term effects of music therapy, dose-response relationships, as well as the relevance of outcomes measures in relation to music therapy.

More than a Museum: Natural History is Relevant in 21st Century Environmental Science

NASA Astrophysics Data System (ADS)

Hernandez, R. R.; Murphy-Mariscal, M. L.; Barrows, C. W.

2015-12-01

In the Anthropocene, the relevancy of natural history in environmental science is challenged and marginalized today more than ever. We tested the hypothesis that natural history is relevant to the fields of environmental science and ecology by assessing the values, needs, and decisions related to natural history of graduate students and environmental science professionals across 31 universities and various employers, respectively, in California. Graduate students surveyed (93.3%) agreed that natural history was relevant to science, approximately 70% believed it "essential" for conducting field-based research; however, 54.2% felt inadequately trained to teach a natural history course and would benefit from additional training in natural history (> 80%). Of the 185 professionals surveyed, all felt that natural history was relevant to science and "essential" or "desirable" in their vocation (93%). Our results indicate a disconnect between the value and relevancy of natural history in 21st century ecological science and opportunities for gaining those skills and knowledge through education and training.

Life Events and Depressive Symptoms in African American Adolescents: Do Ecological Domains and Timing of Life Events Matter?

ERIC Educational Resources Information Center

Sanchez, Yadira M.; Lambert, Sharon F.; Ialongo, Nicholas S.

2012-01-01

Considerable research has documented associations between adverse life events and internalizing symptoms in adolescents, but much of this research has focused on the number of events experienced, with less attention to the ecological context or timing of events. This study examined life events in three ecological domains relevant to adolescents…

Active biomonitoring in freshwater environments: early warning signals from biomarkers in assessing biological effects of diffuse sources of pollutants

NASA Astrophysics Data System (ADS)

Wepener, V.; van Vuren, J. H. J.; Chatiza, F. P.; Mbizi, Z.; Slabbert, L.; Masola, B.

Effluents are a main source of direct and continuous input of pollutants in aquatic ecosystems. Relating observed effects to specific pollutants or even classes of pollutants remains a very difficult task due to the usually unknown, complex and often highly variable composition of effluents. It is recognized that toxicants interfere with organism integrity at the biochemical level and give rise to effects at the individual level and is manifested in reduced ecologically relevant characteristics such as growth, reproduction and survival, and ultimately at the ecosystem level. By integrating multiple endpoints at different ecologically relevant levels of organization within one test organism, it should be possible to gain understanding in how different levels of organization within this organism respond to toxic exposure and how responses at these different levels are interrelated. This paper presents results from a field study in the Rietvlei Wetland system, Gauteng, South Africa using the freshwater mollusk ( Melanoides tuberculata) and freshwater fish ( Oreochromis mossambicus) as bioindicator organisms. Active biomonitoring (ABM) exposures were conducted where organisms were exposed for 28 days in an effluent dominated river during high flow conditions in April 2003. The river receives effluent from a wastewater treatment plant and an industrial complex, so that up to 75% of the total flow of the river is effluent-based. Effects of field exposure were determined using cellular biomarkers e.g. DNA damage, HSP 70, metallothionein, acetylcholine esterase, lactate dehydrogenase and ethoxyresorufin-o-deethylase activity. The results clearly indicate that although the traditional mortality-based whole effluent toxicity testing did not indicate any toxicity, the in situ exposed organisms were stressed. A multivariate statistical approach was particularly useful for integrating the biomarker responses and highlighting sites at which more detailed analysis of chemical contamination would be useful. Based on the individual biomarker results’ contributing towards the distinct groupings it is possible to conclude that Site 1 is subjected to organic pollutants, whereas Sites 2 and 3 undergo a combination of metallic and organic pollutant stress. However, it is essential that a rapid and sensitive biomarker that is representative of the responses of a suite of biomarkers be tested before ABM can be implemented as a routine biomonitoring practice in water resource management.

Essential Annotation Schema for Ecology (EASE)-A framework supporting the efficient data annotation and faceted navigation in ecology.

PubMed

Pfaff, Claas-Thido; Eichenberg, David; Liebergesell, Mario; König-Ries, Birgitta; Wirth, Christian

2017-01-01

Ecology has become a data intensive science over the last decades which often relies on the reuse of data in cross-experimental analyses. However, finding data which qualifies for the reuse in a specific context can be challenging. It requires good quality metadata and annotations as well as efficient search strategies. To date, full text search (often on the metadata only) is the most widely used search strategy although it is known to be inaccurate. Faceted navigation is providing a filter mechanism which is based on fine granular metadata, categorizing search objects along numeric and categorical parameters relevant for their discovery. Selecting from these parameters during a full text search creates a system of filters which allows to refine and improve the results towards more relevance. We developed a framework for the efficient annotation and faceted navigation in ecology. It consists of an XML schema for storing the annotation of search objects and is accompanied by a vocabulary focused on ecology to support the annotation process. The framework consolidates ideas which originate from widely accepted metadata standards, textbooks, scientific literature, and vocabularies as well as from expert knowledge contributed by researchers from ecology and adjacent disciplines.

An RDF version of the VO Registry Version 1.00

NASA Astrophysics Data System (ADS)

Gray, Norman; Gray, Norman

2007-09-01

We describe the initial implementation of an RDF version of the IVOA Resource Registry, serving the registry data via a SPARQL query endpoint, including the creation of the ontology analogues of an important subset of the relevant XML Schemas, and the mechanics of the conversion process. The result is an experimental service, and this is an interim document.

Predicting adult fish acute lethality with the zebrafish embryo: relevance of test duration, endpoints, compound properties, and exposure concentration analysis.

PubMed

Knöbel, Melanie; Busser, Frans J M; Rico-Rico, Angeles; Kramer, Nynke I; Hermens, Joop L M; Hafner, Christoph; Tanneberger, Katrin; Schirmer, Kristin; Scholz, Stefan

2012-09-04

The zebrafish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, which is required by various regulations for environmental risk assessment of chemicals. We investigated the reliability of the embryo test by probing organic industrial chemicals with a wide range of physicochemical properties, toxicities, and modes of toxic action. Moreover, the relevance of using measured versus nominal (intended) exposure concentrations, inclusion of sublethal endpoints, and different exposure durations for the comparability with reported fish acute toxicity was explored. Our results confirm a very strong correlation of zebrafish embryo to fish acute toxicity. When toxicity values were calculated based on measured exposure concentrations, the slope of the type II regression line was 1 and nearly passed through the origin (1 to 1 correlation). Measured concentrations also explained several apparent outliers. Neither prolonged exposure (up to 120 h) nor consideration of sublethal effects led to a reduced number of outliers. Yet, two types of compounds were less lethal to embryos than to adult fish: a neurotoxic compound acting via sodium channels (permethrin) and a compound requiring metabolic activation (allyl alcohol).

Land Management in the Anthropocene: Is History Still Relevant?

NASA Astrophysics Data System (ADS)

Safford, Hugh D.; Betancourt, Julio L.; Hayward, Gregory D.; Wiens, John A.; Regan, Claudia M.

2008-09-01

Incorporating Historical Ecology and Climate Change Into Land Management; Lansdowne, Virginia, 22-25 April 2008; Ecological restoration, conservation, and land management are often based on comparisons with reference sites or time periods, which are assumed to represent ``natural'' or ``properly functioning'' conditions. Such reference conditions can provide a vision of the conservation or management goal and a means to measure progress toward that vision. Although historical ecology has been used successfully to guide resource management in many parts of the world, the continuing relevance of history is now being questioned. Some scientists doubt that lessons from the past can inform management in what may be a dramatically different future, given profound climate change, accelerated land use, and an onslaught of plant and animal invasions.

Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia

PubMed Central

Macciò, Antonio; Madeddu, Clelia; Serpe, Roberto; Massa, Elena; Dessì, Mariele; Panzone, Filomena; Contu, Paolo

2010-01-01

Purpose. A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia—lean body mass (LBM), resting energy expenditure (REE), and fatigue—and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. Patients and Methods. Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months. Results. Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. Conclusion. The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents. PMID:20156909

Exploring possible mechanisms of action for the nanotoxicity and protein binding of decorated nanotubes: interpretation of physicochemical properties from optimal QSAR models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esposito, Emilio Xavier, E-mail: emilio@exeResearch.com; The Chem21 Group, Inc., 1780 Wilson Drive, Lake Forest, IL 60045; Hopfinger, Anton J., E-mail: hopfingr@gmail.com

2015-10-01

Carbon nanotubes have become widely used in a variety of applications including biosensors and drug carriers. Therefore, the issue of carbon nanotube toxicity is increasingly an area of focus and concern. While previous studies have focused on the gross mechanisms of action relating to nanomaterials interacting with biological entities, this study proposes detailed mechanisms of action, relating to nanotoxicity, for a series of decorated (functionalized) carbon nanotube complexes based on previously reported QSAR models. Possible mechanisms of nanotoxicity for six endpoints (bovine serum albumin, carbonic anhydrase, chymotrypsin, hemoglobin along with cell viability and nitrogen oxide production) have been extracted frommore » the corresponding optimized QSAR models. The molecular features relevant to each of the endpoint respective mechanism of action for the decorated nanotubes are also discussed. Based on the molecular information contained within the optimal QSAR models for each nanotoxicity endpoint, either the decorator attached to the nanotube is directly responsible for the expression of a particular activity, irrespective of the decorator's 3D-geometry and independent of the nanotube, or those decorators having structures that place the functional groups of the decorators as far as possible from the nanotube surface most strongly influence the biological activity. These molecular descriptors are further used to hypothesize specific interactions involved in the expression of each of the six biological endpoints. - Highlights: • Proposed toxicity mechanism of action for decorated nanotubes complexes • Discussion of the key molecular features for each endpoint's mechanism of action • Unique mechanisms of action for each of the six biological systems • Hypothesized mechanisms of action based on QSAR/QNAR predictive models.« less

Midcourse correction to a clinical trial when the event rate is underestimated: the Look AHEAD (Action for Health in Diabetes) Study.

PubMed

Brancati, Frederick L; Evans, Mary; Furberg, Curt D; Geller, Nancy; Haffner, Steven; Kahn, Steven E; Kaufmann, Peter G; Lewis, Cora E; Nathan, David M; Pitt, Bertram; Safford, Monika M

2012-02-01

The Look AHEAD (Action for Health in Diabetes) Study is a long-term clinical trial that aims to determine the cardiovascular disease (CVD) benefits of an intensive lifestyle intervention (ILI) in obese adults with type 2 diabetes. The study was designed to have 90% statistical power to detect an 18% reduction in the CVD event rate in the ILI Group compared to the Diabetes Support and Education (DSE) Group over 10.5 years of follow-up. The original power calculations were based on an expected CVD rate of 3.125% per year in the DSE group; however, a much lower-than-expected rate in the first 2 years of follow-up prompted the Data and Safety Monitoring Board (DSMB) to recommend that the Steering Committee undertake a formal blinded evaluation of these design considerations. The Steering Committee created an Endpoint Working Group (EPWG) that consisted of individuals masked to study data to examine relevant issues. The EPWG considered two primary options: (1) expanding the definition of the primary endpoint and (2) extending follow-up of participants. Ultimately, the EPWG recommended that the Look AHEAD Steering Committee approve both strategies. The DSMB accepted these modifications, rather than recommending that the trial continue with inadequate statistical power. Trialists sometimes need to modify endpoints after launch. This decision should be well justified and should be made by individuals who are fully masked to interim results that could introduce bias. This article describes this process in the Look AHEAD study and places it in the context of recent articles on endpoint modification and recent trials that reported endpoint modification.

Ecological Dimensions of Information Literacy

ERIC Educational Resources Information Center

Steinerova, Jela

2010-01-01

Introduction: We examine relationships between information literacy and information ecology with regard to conceptual innovation in information science. We aim to expand our understanding of human information behaviour and relevance assessment in the electronic environment. Method: Conceptual analysis and conceptual mapping is used and…

Amphibian molecular ecology and how it has informed conservation.

PubMed

McCartney-Melstad, Evan; Shaffer, H Bradley

2015-10-01

Molecular ecology has become one of the key tools in the modern conservationist's kit. Here we review three areas where molecular ecology has been applied to amphibian conservation: genes on landscapes, within-population processes, and genes that matter. We summarize relevant analytical methods, recent important studies from the amphibian literature, and conservation implications for each section. Finally, we include five in-depth examples of how molecular ecology has been successfully applied to specific amphibian systems. © 2015 John Wiley & Sons Ltd.

Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?

PubMed Central

Robey, R.Brooks; Weisz, Judith; Kuemmerle, Nancy; Salzberg, Anna C.; Berg, Arthur; Brown, Dustin G.; Kubik, Laura; Palorini, Roberta; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Colacci, Annamaria; Mondello, Chiara; Raju, Jayadev; Woodrick, Jordan; Scovassi, A.Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Hamid, Roslida A.; Williams, Graeme P.; Lowe, Leroy; Meyer, Joel; Martin, Francis L.; Bisson, William H.; Chiaradonna, Ferdinando; Ryan, Elizabeth P.

2015-01-01

Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested. PMID:26106140

Application of the Stable Isotope Label Approach in Clinical Development-Supporting Dissolution Specifications for a Commercial Tablet Product with Tafenoquine, a Long Half-life Compound.

PubMed

Goyal, Navin; Mohamed, Khadeeja; Rolfe, Katie; Sahota, Satty; Ernest, Terry; Duparc, Stephan; Taylor, Maxine; Casillas, Linda; Koh, Gavin C K W

2018-06-04

Bioavailability/bioequivalence studies supporting clinical drug development or commercial supply of drug formulations are often time, cost, and resource intensive. The drug's pharmacokinetic (PK) variability, systemic half-life, and safety issues may pose additional challenges. The stable isotope label (SIL) approach provides a useful tool to significantly reduce the study size in clinical PK studies. Tafenoquine (TQ) is an 8-aminoquinoline under development for preventing Plasmodium vivax malaria relapse. This SIL study assessed the impact of differences in the in vitro dissolution profiles on in vivo exposure of TQ tablets. Fourteen healthy volunteers received a single dose of 300 mg TQ Intermediate Aged or 300 mg TQ Control formulations in this single-center, two-arm, randomized, open-label, parallel-group study. Endpoints included the geometric means ratio of the area under the concentration-time curve (AUC (0-t) and AUC (0-∞) ; primary endpoint) and maximum plasma concentration (C max ) for Intermediate Aged versus Control TQ; correlation of PK parameters for venous versus peripheral (via microsample) blood samples; and safety and tolerability endpoints. Geometric mean ratios for PK parameters (AUC and C max ) and their 90% confidence intervals fell well within standard bioequivalence limits (0.80-1.25). Only one mild adverse event (skin abrasion) was reported. In summary, this SIL methodology-based study demonstrates that the observed differences in the in vitro dissolution profiles between the Control and Intermediate Aged TQ tablets have no clinically relevant effect on systemic TQ exposure. The SIL approach was successfully implemented to enable the setting of a clinically relevant dissolution specification. This study (GSK study number 201780) is registered at clinicaltrials.gov with identifier NCT02751294.

Effects of the pharmaceuticals gemfibrozil and diclofenac on biomarker expression in the zebra mussel (Dreissena polymorpha) and their comparison with standardised toxicity tests.

PubMed

Quinn, Brian; Schmidt, Wiebke; O'Rourke, Kathleen; Hernan, Robert

2011-07-01

Pharmaceuticals, including the lipid regulator gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac have been identified in waste water treatment plant effluents and receiving waters throughout the western world. The acute and chronic toxicity of these compounds was assessed for three freshwater species (Daphnia magna, Pseudokirchneriella subcapitata, Lemna minor) using standardised toxicity tests with toxicity found in the non-environmentally relevant mid mg L(-1) concentration range. For the acute endpoints (IC(50) and EC(50)) gemfibrozil showed higher toxicity ranging from 29 to 59 mg L(-1) (diclofenac 47-67 mg L(-1)), while diclofenac was more toxic for the chronic D. magna 21 d endpoints ranging from 10 to 56 mg L(-1) (gemfibrozil 32-100 mg L(-1)). These results were compared with the expression of several biomarkers in the zebra mussel (Dreissena polymorpha) 24 and 96 h after exposure by injection to concentrations of 21 and 21,000 μg L(-1) corresponding to nominal concentrations of 1 and 1000 μg L(-1). Exposure to gemfibrozil and diclofenac at both concentrations significantly increased the level of lipid peroxidation, a biomarker of damage. At the elevated nominal concentration of 1000 μg L(-1) the biomarkers of defence glutathione transferase and metallothionein were significantly elevated for gemfibrozil and diclofenac respectively, as was DNA damage after 96 h exposure to gemfibrozil. No evidence of endocrine disruption was observed using the alkali-labile phosphate technique. Results from this suite of biomarkers indicate these compounds can cause significant stress at environmentally relevant concentrations acting primarily through oxidation pathways with significant destabilization of the lysosomal membrane and that biomarker expression is a more sensitive endpoint than standardised toxicity tests. Copyright © 2011 Elsevier Ltd. All rights reserved.

Methodological basis for the optimization of a marine sea-urchin embryo test (SET) for the ecological assessment of coastal water quality.

PubMed

Saco-Alvarez, Liliana; Durán, Iria; Ignacio Lorenzo, J; Beiras, Ricardo

2010-05-01

The sea-urchin embryo test (SET) has been frequently used as a rapid, sensitive, and cost-effective biological tool for marine monitoring worldwide, but the selection of a sensitive, objective, and automatically readable endpoint, a stricter quality control to guarantee optimum handling and biological material, and the identification of confounding factors that interfere with the response have hampered its widespread routine use. Size increase in a minimum of n=30 individuals per replicate, either normal larvae or earlier developmental stages, was preferred to observer-dependent, discontinuous responses as test endpoint. Control size increase after 48 h incubation at 20 degrees C must meet an acceptability criterion of 218 microm. In order to avoid false positives minimums of 32 per thousand salinity, 7 pH and 2mg/L oxygen, and a maximum of 40 microg/L NH(3) (NOEC) are required in the incubation media. For in situ testing size increase rates must be corrected on a degree-day basis using 12 degrees C as the developmental threshold. Copyright 2010 Elsevier Inc. All rights reserved.

Assessing clinically meaningful treatment effects in controlled trials: chronic migraine as an example.

PubMed

Dodick, David W; Turkel, Catherine C; DeGryse, Ronald E; Diener, Hans-Christoph; Lipton, Richard B; Aurora, Sheena K; Nolan, Marissa E; Silberstein, Stephen D

2015-02-01

In addition to headache, persons with chronic migraine (CM) experience multiple symptoms, both ictal and interictal, that may contribute to their suffering. Translating clinical trial results into practice requires assessment of the results' clinical meaningfulness. When examining treatment benefit in this disabled patient population, multiple headache-symptom measures should be considered to fully reflect clinical relevance. Currently, only onabotulinumtoxinA is approved specifically for headache prophylaxis in adults with CM. Topiramate is the only other therapeutic agent with double-blind, placebo-controlled evidence in this population. Herein we evaluate the clinical meaningfulness of onabotulinumtoxinA and topiramate as headache prophylaxis in CM by comparing primary endpoints from the placebo-controlled, double-blind phase of the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program and the topiramate clinical trial (frequency of headache days [primary endpoint in PREEMPT; secondary in topiramate trial] and migraine/migrainous days [primary in topiramate trial, or "migraine/probable-migraine days"; secondary in PREEMPT]). Additionally, outcome measures such as responder rates, health-related quality of life, discontinuation rates, safety, and tolerability profiles are important clinical considerations. The clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate. These data support these treatments as meaningful headache prophylaxis in adults with CM. CM is a chronic pain condition. We sought to determine the clinical relevance of recent trials in this disabled population. Clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate, and support use of these treatments as meaningful headache prophylaxis in CM. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE.

PubMed

Lassen, M R; Fisher, W; Mouret, P; Agnelli, G; George, D; Kakkar, A; Mismetti, P; Turpie, A G G

2012-05-01

Semuloparin is a novel ultra-low-molecular-weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients. Three Phase III studies compared semuloparin and enoxaparin after major orthopedic surgery: elective knee replacement (SAVE-KNEE), elective hip replacement (SAVE-HIP1) and hip fracture surgery (SAVE-HIP2). All studies were multinational, randomized and double-blind. Semuloparin and enoxaparin were administered for 7-10 days after surgery. Mandatory bilateral venography was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non-fatal pulmonary embolism or all-cause death. Safety outcomes included major bleeding, clinically relevant non-major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM). In total, 1150, 2326 and 1003 patients were randomized in SAVE-KNEE, SAVE-HIP1 and SAVE-HIP2, respectively. In all studies, the incidences of the primary efficacy endpoint were numerically lower in the semuloparin group vs. the enoxaparin group, but the difference was statistically significant only in SAVE-HIP1. In SAVE-HIP1, clinically relevant bleeding and major bleeding were significantly lower in the semuloparin vs. the enoxaparin group. In SAVE-KNEE and SAVE-HIP2, clinically relevant bleeding tended to be higher in the semuloparin group, but rates of major bleeding were similar in the two groups. Other safety parameters were generally similar between treatment groups. Semuloparin was superior to enoxaparin for VTE prevention after hip replacement surgery, but failed to demonstrate superiority after knee replacement surgery and hip fracture surgery. Semuloparin and enoxaparin exhibited generally similar safety profiles. © 2012 International Society on Thrombosis and Haemostasis.

Brief communication: the ecosystem perspective in ecotoxicology as a way forward for the ecological risk assessment of chemicals.

PubMed

De Laender, Frederik; Janssen, Colin R

2013-07-01

One of the objectives of the European Union (EU) ecological risk assessment of chemicals (ERA) is to derive maximum environmental concentrations that are not expected to cause adverse ecological effects. To this end, related EU directives list protection goals as well as guidelines that should be used to reach these goals. It is generally accepted that the individual-level endpoints on which these guidelines are based do not correspond to the listed population- and ecosystem-level protection goals. In this article, we identify 5 research topics that are key to bridging this gap: 1) the refinement of population-level effects and recovery rates by explicitly taking into account competition and 2) predation, 3) the assessment of chemical effects on biodiversity, 4) the assessment of chemical stress on ecosystem functions and services, and 5) the quantification of the effects of chemical mixtures. In addition, we illustrate why an ecosystem perspective is needed to address these topics and to inform the risk assessment process. We propose the use of existing ecotoxicological community, food web, and ecosystem models to tackle these issues and discuss why new models are needed to predict chemical effects on biodiversity. Copyright © 2013 SETAC.

Disease Dynamics in Ants: A Critical Review of the Ecological Relevance of Using Generalist Fungi to Study Infections in Insect Societies.

PubMed

Loreto, R G; Hughes, D P

2016-01-01

It is assumed that social life can lead to the rapid spread of infectious diseases and outbreaks. In ants, disease outbreaks are rare and the expression of collective behaviors is invoked to explain the absence of epidemics in natural populations. Here, we address the ecological approach employed by many studies that have notably focused (89% of the studies) on two genera of generalist fungal parasites (Beauveria and Metarhizium). We ask whether these are the most representative models to study the evolutionary ecology of ant-fungal parasite interactions. To assess this, we critically examine the literature on ants and their interactions with fungal parasites from the past 114years (1900-2014). We discuss how current evolutionary ecology approaches emerged from studies focused on the biological control of pest ants. We also analyzed the ecological relevance of the laboratory protocols used in evolutionary ecology studies employing generalist parasites, as well as the rare natural occurrence of these parasites on ants. After a detailed consideration of all the publications, we suggest that using generalist pathogens such as Beauveria and Metarhizium is not an optimal approach if the goal is to study the evolutionary ecology of disease in ants. We conclude by advocating for approaches that incorporate greater realism. Copyright © 2016 Elsevier Inc. All rights reserved.

Review of Dredging Elutriate Application Factors: Relevance to Acute-to-Chronic Protection, Contaminant, and Endpoint Specificity

DTIC Science & Technology

2015-07-01

Postma et al. 2002). Unionized ammonia (NH3) is more toxic relative to the ammonium ion ( NH4 +) (USEPA 1989, 1999a, 2009). The fraction of total...ammonia (i.e., sum concentration of NH4 + and NH3) that is unionized ammonia (UIA) is contingent on the pH, temperature, and salinity of the test water

Novel scalable 3D cell based model for in vitro neurotoxicity testing: Combining human differentiated neurospheres with gene expression and functional endpoints.

PubMed

Terrasso, Ana Paula; Pinto, Catarina; Serra, Margarida; Filipe, Augusto; Almeida, Susana; Ferreira, Ana Lúcia; Pedroso, Pedro; Brito, Catarina; Alves, Paula Marques

2015-07-10

There is an urgent need for new in vitro strategies to identify neurotoxic agents with speed, reliability and respect for animal welfare. Cell models should include distinct brain cell types and represent brain microenvironment to attain higher relevance. The main goal of this study was to develop and validate a human 3D neural model containing both neurons and glial cells, applicable for toxicity testing in high-throughput platforms. To achieve this, a scalable bioprocess for neural differentiation of human NTera2/cl.D1 cells in stirred culture systems was developed. Endpoints based on neuronal- and astrocytic-specific gene expression and functionality in 3D were implemented in multi-well format and used for toxicity assessment. The prototypical neurotoxicant acrylamide affected primarily neurons, impairing synaptic function; our results suggest that gene expression of the presynaptic marker synaptophysin can be used as sensitive endpoint. Chloramphenicol, described as neurotoxicant affected both cell types, with cytoskeleton markers' expression significantly reduced, particularly in astrocytes. In conclusion, a scalable and reproducible process for production of differentiated neurospheres enriched in mature neurons and functional astrocytes was obtained. This 3D approach allowed efficient production of large numbers of human differentiated neurospheres, which in combination with gene expression and functional endpoints are a powerful cell model to evaluate human neuronal and astrocytic toxicity. Copyright © 2014 Elsevier B.V. All rights reserved.

Assessing correlations between the spatial distribution of the dose to the rectal wall and late rectal toxicity after prostate radiotherapy: an analysis of data from the MRC RT01 trial (ISRCTN 47772397)

NASA Astrophysics Data System (ADS)

Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Sydes, Matthew R.; Dearnaley, David P.; Partridge, Mike

2009-11-01

Many studies have been performed to assess correlations between measures derived from dose-volume histograms and late rectal toxicities for radiotherapy of prostate cancer. The purpose of this study was to quantify correlations between measures describing the shape and location of the dose distribution and different outcomes. The dose to the rectal wall was projected on a two-dimensional map. In order to characterize the dose distribution, its centre of mass, longitudinal and lateral extent, and eccentricity were calculated at different dose levels. Furthermore, the dose-surface histogram (DSH) was determined. Correlations between these measures and seven clinically relevant rectal-toxicity endpoints were quantified by maximally selected standardized Wilcoxon rank statistics. The analysis was performed using data from the RT01 prostate radiotherapy trial. For some endpoints, the shape of the dose distribution is more strongly correlated with the outcome than simple DSHs. Rectal bleeding was most strongly correlated with the lateral extent of the dose distribution. For loose stools, the strongest correlations were found for longitudinal extent; proctitis was most strongly correlated with DSH. For the other endpoints no statistically significant correlations could be found. The strengths of the correlations between the shape of the dose distribution and outcome differed considerably between the different endpoints. Due to these significant correlations, it is desirable to use shape-based tools in order to assess the quality of a dose distribution.

Tools in the assessment of sarcopenia

PubMed Central

Cooper, C; Fielding, R; Visser, M; van Loon, LJ; Rolland, Y; Orwoll, E; Reid, K; Boonen, S; Dere, W; Epstein, S; Mitlak, B; Tsouderos, Y; Sayer, AA; Rizzoli, R; Reginster, JY; Kanis, JA

2013-01-01

Summary This review provides a framework for development of an operational definition of sarcopenia and of the potential endpoints that might be adopted in clinical trials among older adults. Introduction While the clinical relevance of sarcopenia is widely recognized, there is currently no universally accepted definition of the disorder. The development of interventions to alter the natural history of sarcopenia also requires consensus on the most appropriate endpoints for determining outcomes of clinical importance which might be utilised in intervention studies. Methods and results We review current approaches to the definition of sarcopenia, and the methods used for the assessment of various aspects of physical function in older people. The potential endpoints of muscle mass, muscle strength, muscle power and muscle fatigue, as well as the relationships between them, are explored with reference to the availability and practicality of the available methods for measuring these endpoints in clinical trials. Conclusions Based on current evidence, none of the four potential outcomes in question is sufficiently comprehensive to recommend as a uniform single outcome in randomised clinical trials. We propose that sarcopenia may be optimally defined (for the purposes of clinical trial inclusion criteria, as well as epidemiological studies) using a combination of measures of muscle mass and physical performance. The choice of outcome measures for clinical trials in sarcopenia is more difficult; co-primary outcomes, tailored to the specific intervention in question, may be the best way forward in this difficult but clinically important area. PMID:23842964

Land management in the Anthropocene: is history still relevant?: Incorporating historical ecology and climate change into land management; Lansdowne, Virginia, 22–25 April 2008

USGS Publications Warehouse

Safford, Hugh D.; Betancourt, Julio L.; Hayward, Gregory D.; Wiens, John A.; Regan, Claudia M.

2008-01-01

Ecological restoration, conservation, and land management are often based on comparisons with reference sites or time periods, which are assumed to represent “natural” or “properly functioning” conditions. Such reference conditions can provide a vision of the conservation or management goal and a means to measure progress toward that vision. Although historical ecology has been used successfully to guide resource management in many parts of the world, the continuing relevance of history is now being questioned. Some scientists doubt that lessons from the past can inform management in what may be a dramatically different future, given profound climate change, accelerated land use, and an onslaught of plant and animal invasions.

Exploring vegetation in the fourth dimension.

PubMed

Mitchell, Fraser J G

2011-01-01

Much ecological research focuses on changes in vegetation on spatial scales from stands to landscapes; however, capturing data on vegetation change over relevant timescales remains a challenge. Pollen analysis offers unrivalled access to data with global coverage over long timescales. Robust techniques have now been developed that enable pollen data to be converted into vegetation data in terms of individual taxa, plant communities or biomes, with the possibility of deriving from those data a range of plant attributes and ecological indicators. In this review, I discuss how coupling pollen with macrofossil, charcoal and genetic data opens up the extensive pollen databases to investigation of the drivers of vegetation change over time and also provides extensive data sets for testing hypotheses with wide ecological relevance. © 2010 Elsevier Ltd. All rights reserved.

Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna.

PubMed

Haeba, Maher H; Hilscherová, Klára; Mazurová, Edita; Bláha, Ludek

2008-05-01

Pollution-induced endocrine disruption in vertebrates and invertebrates is a worldwide environmental problem, but relatively little is known about effects of endocrine disrupting compounds (EDCs) in planktonic crustaceans (including Daphnia magna). Aims of the present study were to investigate acute 48 h toxicity and sub-chronic (4-6 days) and chronic (21 days) effects of selected EDCs in D. magna. We have investigated both traditional endpoints as well as other parameters such as sex determination, maturation, molting or embryogenesis in order to evaluate the sensitivity and possible use of these endpoints in ecological risk assessment. We have studied effects of four model EDCs (vinclozolin, flutamide, ketoconazole and dicofol) on D. magna using (i) an acute 48 h immobilization assay, (ii) a sub-chronic, 4-6 day assay evaluating development and the sex ratio of neonates, and (iii) a chronic, 21 day assay studying number of neonates, sex of neonates, molting frequency, day of maturation and the growth of maternal organisms. Acute EC50 values in the 48 h immobilization test were as follows (mg/L): dicofol 0.2, ketoconazole 1.5, flutamide 2.7, vinclozolin >3. Short-term, 4-6 day assays with sublethal concentrations showed that the sex ratio in Daphnia was modulated by vinclozolin (decreased number of neonate males at 1 mg/L) and dicofol (increase in males at 0.1 mg/L). Flutamide (up to 1 mg/L) had no effect on the sex of neonates, but inhibited embryonic development at certain stages during chronic assay, resulting in abortions. Ketoconazole had no significant effects on the studied processes up to 1 mg/L. Sex ratio modulations by some chemicals (vinclozolin and dicofol) corresponded to the known action of these compounds in vertebrates (i.e. anti-androgenicity and anti-oestrogenicity, respectively). Our study revealed that some chemicals known to affect steroid-regulated processes in vertebrates can also affect sublethal endpoints (e.g. embryonic sex determination and/or reproduction) in invertebrates such as D. magna. A series of model vertebrate endocrine disrupters affected various sub-chronic and chronic parameters in D. magna including several endpoints that have not been previously studied in detail (such as sex determination in neonates, embryogenesis, molting and maturation). Evaluations of traditional reproduction parameters (obtained from the 21 day chronic assay). as well as the results from a rapid, 4-6 day, sub-chronic assay provide complementary information on non-lethal effects of suspected organic endocrine disrupters. It seems that there are analogies between vertebrates and invertebrates in toxicity mechanisms and in vivo effects of endocrine disruptors. However, general physiological status of organisms may also indirectly affect endpoints that are traditionally considered 'hormone regulated' (especially at higher effective concentrations as observed in this study) and these factors should be carefully considered. Further research of D. magna physiology and comparative studies with various EDCs will help to understand mechanisms of action as well as ecological risks of EDCs in the environment.

Ecology, Pollution, Environment.

ERIC Educational Resources Information Center

Turk, Amos; And Others

Elements of environmental science and how the science is related to the more traditionally established disciplines are explored in this supplementary text. Two aspects of environmental science are considered--subject matter and decision making. Relevant background material in the physical sciences is presented under the following topics: ecology,…

Weighing the evidence of ecological risk from chemical contamination in the estuarine environment adjacent to the Portsmouth Naval Shipyard, Kittery, Maine, USA.

PubMed

Johnston, Robert K; Munns, Wayne R; Tyler, Patti Lynne; Marajh-Whittemore, Patty; Finkelstein, Kenneth; Munney, Kenneth; Short, Fred T; Melville, Ann; Hahn, Simeon P

2002-01-01

In characterizing ecological risks, considerable consensus building and professional judgments are required to develop conclusions about risk. This is because how to evaluate all the factors that determine ecological risk is not well defined and is subject to interpretation. Here we report on the application of a procedure to weigh the evidence of ecological risk and develop conclusions about risk that will incorporate the strengths and weaknesses of the assessment. The procedure was applied to characterize ecological risk of chemical contamination in nearshore areas adjacent to the Portsmouth Naval Shipyard, located at the mouth of the Great Bay Estuary, New Hampshire and Maine, USA. Measures of exposure and effect were used to interpret the magnitude of risk to the assessment endpoints of pelagic species, epibenthic species, the benthic community, eelgrass plants, the salt marsh community, and avian receptors. The evidence of chemical exposure from water, sediment, and tissue and the evidence of biological effects to representative pelagic, epibenthic, benthic, eelgrass, salt marsh, and avian species were weighed to characterize ecological risk. Individual measures were weighted by the quality and reliability of their data and risk was estimated from the preponderance, magnitude, extent, and strength of causal relationships between the data on exposure and effects. Relating evidence of risk to hypothesized pathways of exposure made it possible to estimate the magnitude of risk from sediment and water and express the confidence associated with the findings. Systematically weighing the evidence of risk rendered conclusions about risk in a manner that was clearly defined, objective, consistent, and did not rely solely on professional judgment.

Essential Annotation Schema for Ecology (EASE)—A framework supporting the efficient data annotation and faceted navigation in ecology

PubMed Central

Eichenberg, David; Liebergesell, Mario; König-Ries, Birgitta; Wirth, Christian

2017-01-01

Ecology has become a data intensive science over the last decades which often relies on the reuse of data in cross-experimental analyses. However, finding data which qualifies for the reuse in a specific context can be challenging. It requires good quality metadata and annotations as well as efficient search strategies. To date, full text search (often on the metadata only) is the most widely used search strategy although it is known to be inaccurate. Faceted navigation is providing a filter mechanism which is based on fine granular metadata, categorizing search objects along numeric and categorical parameters relevant for their discovery. Selecting from these parameters during a full text search creates a system of filters which allows to refine and improve the results towards more relevance. We developed a framework for the efficient annotation and faceted navigation in ecology. It consists of an XML schema for storing the annotation of search objects and is accompanied by a vocabulary focused on ecology to support the annotation process. The framework consolidates ideas which originate from widely accepted metadata standards, textbooks, scientific literature, and vocabularies as well as from expert knowledge contributed by researchers from ecology and adjacent disciplines. PMID:29023519

Randomized multicentre trial comparing external and internal pancreatic stenting during pancreaticoduodenectomy.

PubMed

Jang, J-Y; Chang, Y R; Kim, S-W; Choi, S H; Park, S J; Lee, S E; Lim, C-S; Kang, M J; Lee, H; Heo, J S

2016-05-01

There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF. Patients undergoing elective PD or pylorus-preserving PD with duct-to-mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long-term complications and quality of life 2 years after PD. A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (-2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (-10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent-related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non-pancreatic disease and high body mass index (23·3 kg/m 2 or above) predicted clinically relevant POPF. External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

PubMed

Wallach, Joshua D; Ciani, Oriana; Pease, Alison M; Gonsalves, Gregg S; Krumholz, Harlan M; Taylor, Rod S; Ross, Joseph S

2018-03-21

The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95% CI -0.15-0.16). Many postapproval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection. Although treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on non-continuous surrogate markers of disease are often larger than those observed among postapproval trials using surrogate markers as trial endpoints, there is no evidence of difference between pivotal and postapproval trials using continuous surrogate markers.

Endocrine disrupting chemicals in fish: developing exposure indicators and predictive models of effects based on mechanism of action.

PubMed

Ankley, Gerald T; Bencic, David C; Breen, Michael S; Collette, Timothy W; Conolly, Rory B; Denslow, Nancy D; Edwards, Stephen W; Ekman, Drew R; Garcia-Reyero, Natalia; Jensen, Kathleen M; Lazorchak, James M; Martinović, Dalma; Miller, David H; Perkins, Edward J; Orlando, Edward F; Villeneuve, Daniel L; Wang, Rong-Lin; Watanabe, Karen H

2009-05-05

Knowledge of possible toxic mechanisms (or modes) of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, thereby reducing uncertainties related to extrapolation across species, endpoints and chemical structure. However, MOA-based testing seldom has been used for assessing the ecological risk of chemicals. This is in part because past regulatory mandates have focused more on adverse effects of chemicals (reductions in survival, growth or reproduction) than the pathways through which these effects are elicited. A recent departure from this involves endocrine-disrupting chemicals (EDCs), where there is a need to understand both MOA and adverse outcomes. To achieve this understanding, advances in predictive approaches are required whereby mechanistic changes caused by chemicals at the molecular level can be translated into apical responses meaningful to ecological risk assessment. In this paper we provide an overview and illustrative results from a large, integrated project that assesses the effects of EDCs on two small fish models, the fathead minnow (Pimephales promelas) and zebrafish (Danio rerio). For this work a systems-based approach is being used to delineate toxicity pathways for 12 model EDCs with different known or hypothesized toxic MOA. The studies employ a combination of state-of-the-art genomic (transcriptomic, proteomic, metabolomic), bioinformatic and modeling approaches, in conjunction with whole animal testing, to develop response linkages across biological levels of organization. This understanding forms the basis for predictive approaches for species, endpoint and chemical extrapolation. Although our project is focused specifically on EDCs in fish, we believe that the basic conceptual approach has utility for systematically assessing exposure and effects of chemicals with other MOA across a variety of biological systems.

Community Psychology, Planning, and Learning: A U.S. Perspective on Sustainable Development.

ERIC Educational Resources Information Center

Perkins, Douglas D.

An ecological framework for predicting citizen participation in grassroots community organizations and predicting community disorder problems (such as crime and fear) was developed and tested. The framework, which is called an ecological framework for sustainable community learning and development, delineates the relevant economic, political,…

Ecological Unequal Exchange: International Trade and Uneven Utilization of Environmental Space in the World System

ERIC Educational Resources Information Center

Rice, James

2007-01-01

We evaluate the argument that international trade influences disproportionate cross-national utilization of global renewable natural resources. Such uneven dynamics are relevant to the consideration of inequitable appropriation of environmental space in particular and processes of ecological unequal exchange more generally. Using OLS regression…

Integrated Science Assessment (ISA) for Oxides of Nitrogen and Sulfur - Ecological Criteria (Final Report, Dec 2008)

EPA Science Inventory

EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Oxides of Nitrogen and Sulfur - Ecological Criteria. This document represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the ...

Surprises and insights from long-term aquatic datasets and experiments

Treesearch

Walter K. Dodds; Christopher T. Robinson; Evelyn E. Gaiser; Gretchen J.A. Hansen; Heather Powell; Joseph M. Smith; Nathaniel B. Morse; Sherri L. Johnson; Stanley V. Gregory; Tisza Bell; Timothy K. Kratz; William H. McDowell

2012-01-01

Long-term research on freshwater ecosystems provides insights that can be difficult to obtain from other approaches. Widespread monitoring of ecologically relevant water-quality parameters spanning decades can facilitate important tests of ecological principles. Unique long-term data sets and analytical tools are increasingly available, allowing for powerful and...

Crossing Boundaries in Undergraduate Biology Education

ERIC Educational Resources Information Center

Vanderklein, Dirk; Munakata, Mika; McManus, Jason

2016-01-01

In an effort to make mathematics relevant to biology students, the authors developed two modules that sought to integrate mathematics and ecology instruction to differing degrees. The modules were developed by a team of biology and mathematics educators and were implemented in an ecology course using three different instructional methods for three…

Earthly Matters: Learning Occurs When You Hear the Grass Singing.

ERIC Educational Resources Information Center

Birt, Deborah; Krug, Don H.; Sheridan, Mary

1997-01-01

Discusses the actions and approaches advanced during the 1996 Summer Colloquium, "Art and Ecology: Interdisciplinary Approaches to the Curriculum." Illustrates how action-oriented inquiry makes learning relevant to all people through exploring the poetry of place. The colloquium identified community ecological issues that could be examined through…

Can natural variability trigger effects on fish and fish habitat as defined in environment Canada's metal mining environmental effects monitoring program?

PubMed

Mackey, Robin; Rees, Cassandra; Wells, Kelly; Pham, Samantha; England, Kent

2013-01-01

The Metal Mining Effluent Regulations (MMER) took effect in 2002 and require most metal mining operations in Canada to complete environmental effects monitoring (EEM) programs. An "effect" under the MMER EEM program is considered any positive or negative statistically significant difference in fish population, fish usability, or benthic invertebrate community EEM-defined endpoints. Two consecutive studies with the same statistically significant differences trigger more intensive monitoring, including the characterization of extent and magnitude and investigation of cause. Standard EEM study designs do not require multiple reference areas or preexposure sampling, thus results and conclusions about mine effects are highly contingent on the selection of a near perfect reference area and are at risk of falsely labeling natural variation as mine related "effects." A case study was completed to characterize the natural variability in EEM-defined endpoints during preexposure or baseline conditions. This involved completing a typical EEM study in future reference and exposure lakes surrounding a proposed uranium (U) mine in northern Saskatchewan, Canada. Moon Lake was sampled as the future exposure area as it is currently proposed to receive effluent from the U mine. Two reference areas were used: Slush Lake for both the fish population and benthic invertebrate community surveys and Lake C as a second reference area for the benthic invertebrate community survey. Moon Lake, Slush Lake, and Lake C are located in the same drainage basin in close proximity to one another. All 3 lakes contained similar water quality, fish communities, aquatic habitat, and a sediment composition largely comprised of fine-textured particles. The fish population survey consisted of a nonlethal northern pike (Esox lucius) and a lethal yellow perch (Perca flavescens) survey. A comparison of the 5 benthic invertebrate community effect endpoints, 4 nonlethal northern pike population effect endpoints, and 10 lethal yellow perch effect endpoints resulted in the observation of several statistically significant differences at the future exposure area relative to the reference area and/or areas. When the data from 2 reference areas assessed for the benthic invertebrate community survey were pooled, no significant differences in effect endpoints were observed. These results demonstrate weaknesses in the definition of an "effect" used by the MMER EEM program and in the use of a single reference area. Determination of the ecological significance of statistical differences identified as part of EEM programs conducted during the operational period should consider preexisting (background) natural variability between reference and exposure areas. Copyright © 2012 SETAC.

U.S. Geological Survey Science Support Strategy for Biscayne National Park and Surrounding Areas in Southeastern Florida

USGS Publications Warehouse

Wolfert-Lohmann, Melinda A.; Langevin, Christian D.; Jones, Sonya A.; Reich, Chris D.; Wingard, Georgina L.; Kuffner, Ilsa B.; Cunningham, Kevin J.

2008-01-01

The U.S. Geological Survey conducts a wide range of research in and around the Biscayne National Park region of southern Florida. This research encompasses the biologic, ecologic, meteorologic, geologic, and hydrologic components of the system, including water-quality analyses, ground-water modeling, hydrogeologic-data collection, ecologic-habitat evaluations, wetlands characterizations, biogeochemistry of ecosystems, and paleo-ecologic analyses. Relevant information is provided herein for researchers and managers interested in the Biscayne Bay area and about current U.S. Geological Survey efforts that address important resource protection and management issues. Specifically, managers and scientists are provided with information on current and recently completed U.S. Geological Survey projects and a sample listing of potential U.S. Geological Survey research projects addressing relevant issues that face the study area.

Biodiversity, ecosystem functions and services in environmental risk assessment: introduction to the special issue.

PubMed

Schäfer, Ralf B

2012-01-15

This Special Issue focuses on the questions if and how biodiversity, ecosystem functions and resulting services could be incorporated into the Ecological Risk Assessment (ERA). Therefore, three articles provide a framework for the integration of ecosystem services into ERA of soils, sediments and pesticides. Further articles demonstrate ways how stakeholders can be integrated into an ecosystem service-based ERA for soils and describe how the current monitoring could be adapted to new assessment endpoints that are directly linked to ecosystem services. Case studies show that the current ERA may not be protective for biodiversity, ecosystem functions and resulting services and that both pesticides and salinity currently adversely affect ecosystem functions in the field. Moreover, ecological models can be used for prediction of new protection goals and could finally support their implementation into the ERA. Overall, the Special Issue stresses the urgent need to enhance current procedures of ERA if biodiversity, ecosystem functions and resulting services are to be protected. Copyright © 2011 Elsevier B.V. All rights reserved.

Detecting kinematic boundary surfaces in phase space: particle mass measurements in SUSY-like events

DOE PAGES

Debnath, Dipsikha; Gainer, James S.; Kilic, Can; ...

2017-06-19

We critically examine the classic endpoint method for particle mass determination, focusing on difficult corners of parameter space, where some of the measurements are not independent, while others are adversely affected by the experimental resolution. In such scenarios, mass differences can be measured relatively well, but the overall mass scale remains poorly constrained. Using the example of the standard SUSY decay chain q ~→χ ~ 0 2→ℓ ~→χ ~ 0 1 , we demonstrate that sensitivity to the remaining mass scale parameter can be recovered by measuring the two-dimensional kinematical boundary in the relevant three-dimensional phase space of invariant massesmore » squared. We develop an algorithm for detecting this boundary, which uses the geometric properties of the Voronoi tessellation of the data, and in particular, the relative standard deviation (RSD) of the volumes of the neighbors for each Voronoi cell in the tessellation. We propose a new observable, Σ¯ , which is the average RSD per unit area, calculated over the hypothesized boundary. We show that the location of the Σ¯ maximum correlates very well with the true values of the new particle masses. Our approach represents the natural extension of the one-dimensional kinematic endpoint method to the relevant three dimensions of invariant mass phase space.« less

Detecting kinematic boundary surfaces in phase space: particle mass measurements in SUSY-like events

DOE Office of Scientific and Technical Information (OSTI.GOV)

Debnath, Dipsikha; Gainer, James S.; Kilic, Can

We critically examine the classic endpoint method for particle mass determination, focusing on difficult corners of parameter space, where some of the measurements are not independent, while others are adversely affected by the experimental resolution. In such scenarios, mass differences can be measured relatively well, but the overall mass scale remains poorly constrained. Using the example of the standard SUSY decay chain q ~→χ ~ 0 2→ℓ ~→χ ~ 0 1 , we demonstrate that sensitivity to the remaining mass scale parameter can be recovered by measuring the two-dimensional kinematical boundary in the relevant three-dimensional phase space of invariant massesmore » squared. We develop an algorithm for detecting this boundary, which uses the geometric properties of the Voronoi tessellation of the data, and in particular, the relative standard deviation (RSD) of the volumes of the neighbors for each Voronoi cell in the tessellation. We propose a new observable, Σ¯ , which is the average RSD per unit area, calculated over the hypothesized boundary. We show that the location of the Σ¯ maximum correlates very well with the true values of the new particle masses. Our approach represents the natural extension of the one-dimensional kinematic endpoint method to the relevant three dimensions of invariant mass phase space.« less

Detecting kinematic boundary surfaces in phase space: particle mass measurements in SUSY-like events

NASA Astrophysics Data System (ADS)

Debnath, Dipsikha; Gainer, James S.; Kilic, Can; Kim, Doojin; Matchev, Konstantin T.; Yang, Yuan-Pao

2017-06-01

We critically examine the classic endpoint method for particle mass determination, focusing on difficult corners of parameter space, where some of the measurements are not independent, while others are adversely affected by the experimental resolution. In such scenarios, mass differences can be measured relatively well, but the overall mass scale remains poorly constrained. Using the example of the standard SUSY decay chain \\tilde{q}\\to {\\tilde{χ}}_2^0\\to \\tilde{ℓ}\\to {\\tilde{χ}}_1^0 , we demonstrate that sensitivity to the remaining mass scale parameter can be recovered by measuring the two-dimensional kinematical boundary in the relevant three-dimensional phase space of invariant masses squared. We develop an algorithm for detecting this boundary, which uses the geometric properties of the Voronoi tessellation of the data, and in particular, the relative standard deviation (RSD) of the volumes of the neighbors for each Voronoi cell in the tessellation. We propose a new observable, \\overline{Σ} , which is the average RSD per unit area, calculated over the hypothesized boundary. We show that the location of the \\overline{Σ} maximum correlates very well with the true values of the new particle masses. Our approach represents the natural extension of the one-dimensional kinematic endpoint method to the relevant three dimensions of invariant mass phase space.

The ISS Sensitizing Agents Data Bank (BDS).

PubMed

Brunetto, Barbara; Binetti, Roberto; Ceccarelli, Federica; Costamagna, Francesca Marina; D'Angiolini, Antonella; Fabri, Alessandra; Ferri, Maurizio; Marcello, Ida; Riva, Giovanni; Roazzi, Paolo; Trucchi, Daniela; Tinghino, Raffaella

2008-01-01

The Istituto Superiore Sanità has developed a data bank on sensitizing substances (Banca Dati Sensibilizzanti, BDS), available on website (www.iss.it/bdse/), sharing complete, controlled and updated information coming from different sources, such as scientific publications, international agencies and governmental or non governmental organizations. It is worthwhile that the main objective of the BDS is not the classification of sensitizing or potentially sensitizing agents within specific risk classes, but it is essentially to provide concise and non confidential information related to this endpoint. At present, the BDS includes: all the substances officially classified by European Union, (Annex I to Directive 67/548/EEC), some substances listed in I (Directive 67/548/EEC) for endpoints different than "sensitization" but indicated as sensitizers by other relevant institutions, all the substances indicated as sensitizers by relevant agencies or institutions (ACGIH, DFG), some substances indicted as sensitizers by industry and other non-governmental organizations (ETAD and HERA), all the substances regarded as "potentially sensitizing dyes" by the Commission of the European Community for the award of the eco-label to textile products, some substances for which, even in the absence of any categorization by Union, ACGIH or DFG, it is not possible to exclude a sensitizing potential on the basis of reliable documents.

Extending nonlinear analysis to short ecological time series.

PubMed

Hsieh, Chih-hao; Anderson, Christian; Sugihara, George

2008-01-01

Nonlinearity is important and ubiquitous in ecology. Though detectable in principle, nonlinear behavior is often difficult to characterize, analyze, and incorporate mechanistically into models of ecosystem function. One obvious reason is that quantitative nonlinear analysis tools are data intensive (require long time series), and time series in ecology are generally short. Here we demonstrate a useful method that circumvents data limitation and reduces sampling error by combining ecologically similar multispecies time series into one long time series. With this technique, individual ecological time series containing as few as 20 data points can be mined for such important information as (1) significantly improved forecast ability, (2) the presence and location of nonlinearity, and (3) the effective dimensionality (the number of relevant variables) of an ecological system.

Biomonitoring and risk assessment on earth and during exploratory missions using AquaHab ®

NASA Astrophysics Data System (ADS)

Slenzka, K.; Dünne, M.; Jastorff, B.

2008-12-01

Bioregenerative closed ecological life support systems (CELSS) will be necessary in the exploration context revitalizing atmosphere, waste water and producing food for the human CELSS mates. During these long-term space travels and stays far away from Earth in an hostile environment as well as far for example from any hospital and surgery potential, it will be necessary to know much more about chemical and drug contamination in the special sense and by human's themselves in detail. Additionally, there is a strong need on Earth for more relevant standardized test systems including aquatic ones for the prospective risk assessment of chemicals and drugs in general on a laboratory scale. Current standardized test systems are mono species tests, and thus do not represent system aspects and have reduced environmental relevance. The experience gained during the last years in our research group lead to the development of a self-sustaining closed aquatic habitat/facility, called AquaHab ® which can serve regarding space exploration and Earth application. The AquaHab ® module can be the home of several fish species, snails, plants, amphipods and bacteria. The possibility to use different effect endpoints with certain beneficial characteristics is the basis for the application of AquaHab ® in different fields. Influence of drugs and chemicals can be tested on several trophic levels and ecosystem levels; guaranteeing a high relevance for aquatic systems in the real environment. Analyses of effect parameters of different complexity (e.g. general biological and water chemical parameters, activity of biotransforming enzymes) result in broad spectra of sensitivity. Combined with residual analyses (including all metabolites), this leads to an extended prospective risk assessment of a chemical on Earth and in a closed Life Support System. The possibility to measure also sensitive "online" parameters (e.g. behavior, respiration/photosynthetic activity) enables a quick and sensitive effect analysis of water contaminants in respective environments. AquaHab ® is currently under development to an early warning biomonitoring system using genetically modified fish and green algae. The implementation of biosensors/biochip in addition is also discussed.

Building Interdisciplinary Research Capacity: a Key Challenge for Ecological Approaches in Public Health.

PubMed

Galway, Lindsay P; Parkes, Margot W; Allen, Diana; Takaro, Tim K

2016-01-01

The shortcomings of public health research informed by reductionist and fragmented biomedical approaches and the emergence of wicked problems are fueling a renewed interest in ecological approaches in public health. Despite the central role of interdisciplinarity in the context of ecological approaches in public health research, inadequate attention has been given to the specific challenge of doing interdisciplinary research in practice. As a result, important knowledge gaps exist with regards to the practice of interdisciplinary research. We argue that explicit attention towards the challenge of doing interdisciplinary research is critical in order to effectively apply ecological approaches to public health issues. This paper draws on our experiences developing and conducting an interdisciplinary research project exploring the links among climate change, water, and health to highlight five specific insights which we see as relevant to building capacity for interdisciplinary research specifically, and which have particular relevance to addressing the integrative challenges demanded by ecological approaches to address public health issues. These lessons include: (i) the need for frameworks that facilitate integration; (ii) emphasize learning-by-doing; (iii) the benefits of examining issues at multiple scales; (iv) make the implicit, explicit; and (v) the need for reflective practice. By synthesizing and sharing experiences gained by engaging in interdisciplinary inquiries using an ecological approach, this paper responds to a growing need to build interdisciplinary research capacity as a means for advancing the ecological public health agenda more broadly.

Building Interdisciplinary Research Capacity: a Key Challenge for Ecological Approaches in Public Health

PubMed Central

Galway, Lindsay P.; Parkes, Margot W.; Allen, Diana; Takaro, Tim K.

2016-01-01

The shortcomings of public health research informed by reductionist and fragmented biomedical approaches and the emergence of wicked problems are fueling a renewed interest in ecological approaches in public health. Despite the central role of interdisciplinarity in the context of ecological approaches in public health research, inadequate attention has been given to the specific challenge of doing interdisciplinary research in practice. As a result, important knowledge gaps exist with regards to the practice of interdisciplinary research. We argue that explicit attention towards the challenge of doing interdisciplinary research is critical in order to effectively apply ecological approaches to public health issues. This paper draws on our experiences developing and conducting an interdisciplinary research project exploring the links among climate change, water, and health to highlight five specific insights which we see as relevant to building capacity for interdisciplinary research specifically, and which have particular relevance to addressing the integrative challenges demanded by ecological approaches to address public health issues. These lessons include: (i) the need for frameworks that facilitate integration; (ii) emphasize learning-by-doing; (iii) the benefits of examining issues at multiple scales; (iv) make the implicit, explicit; and (v) the need for reflective practice. By synthesizing and sharing experiences gained by engaging in interdisciplinary inquiries using an ecological approach, this paper responds to a growing need to build interdisciplinary research capacity as a means for advancing the ecological public health agenda more broadly. PMID:29546171

Progression-free survival as a primary endpoint in clinical trials of metastatic colorectal cancer

PubMed Central

Gill, S.; Berry, S.; Biagi, J.; Butts, C.; Buyse, M.; Chen, E.; Jonker, D.; Mărginean, C.; Samson, B.; Stewart, J.; Thirlwell, M.; Wong, R.; Maroun, J.A.

2011-01-01

In recent years, significant advances have been made in the management of metastatic colorectal cancer. Traditionally, an improvement in overall survival has been considered the “gold standard”—the most convincing measure of efficacy. However, overall survival requires larger patient numbers and longer follow-up and may often be confounded by other factors, including subsequent therapies and crossover. Given the number of active therapies for potential investigation, demand for rapid evaluation and early availability of new therapies is growing. Progression-free survival is regarded as an important measure of treatment benefit and, compared with overall survival, can be evaluated earlier, with fewer patients and no confounding by subsequent lines of therapy. The present paper reviews the advantages, limitations, and relevance of progression-free survival as a primary endpoint in randomized trials of metastatic colorectal cancer. PMID:21969810

Classification of Chemicals Based On Structured Toxicity ...

EPA Pesticide Factsheets

Thirty years and millions of dollars worth of pesticide registration toxicity studies, historically stored as hardcopy and scanned documents, have been digitized into highly standardized and structured toxicity data within the Toxicity Reference Database (ToxRefDB). Toxicity-based classifications of chemicals were performed as a model application of ToxRefDB. These endpoints will ultimately provide the anchoring toxicity information for the development of predictive models and biological signatures utilizing in vitro assay data. Utilizing query and structured data mining approaches, toxicity profiles were uniformly generated for greater than 300 chemicals. Based on observation rate, species concordance and regulatory relevance, individual and aggregated effects have been selected to classify the chemicals providing a set of predictable endpoints. ToxRefDB exhibits the utility of transforming unstructured toxicity data into structured data and, furthermore, into computable outputs, and serves as a model for applying such data to address modern toxicological problems.

Toward refined environmental scenarios for ecological risk assessment of down-the-drain chemicals in freshwater environments.

PubMed

Franco, Antonio; Price, Oliver R; Marshall, Stuart; Jolliet, Olivier; Van den Brink, Paul J; Rico, Andreu; Focks, Andreas; De Laender, Frederik; Ashauer, Roman

2017-03-01

Current regulatory practice for chemical risk assessment suffers from the lack of realism in conventional frameworks. Despite significant advances in exposure and ecological effect modeling, the implementation of novel approaches as high-tier options for prospective regulatory risk assessment remains limited, particularly among general chemicals such as down-the-drain ingredients. While reviewing the current state of the art in environmental exposure and ecological effect modeling, we propose a scenario-based framework that enables a better integration of exposure and effect assessments in a tiered approach. Global- to catchment-scale spatially explicit exposure models can be used to identify areas of higher exposure and to generate ecologically relevant exposure information for input into effect models. Numerous examples of mechanistic ecological effect models demonstrate that it is technically feasible to extrapolate from individual-level effects to effects at higher levels of biological organization and from laboratory to environmental conditions. However, the data required to parameterize effect models that can embrace the complexity of ecosystems are large and require a targeted approach. Experimental efforts should, therefore, focus on vulnerable species and/or traits and ecological conditions of relevance. We outline key research needs to address the challenges that currently hinder the practical application of advanced model-based approaches to risk assessment of down-the-drain chemicals. Integr Environ Assess Manag 2017;13:233-248. © 2016 SETAC. © 2016 SETAC.

Use of an activity monitor to detect response to treatment in dogs with osteoarthritis

PubMed Central

Brown, Dorothy Cimino; Boston, Raymond C.; Farrar, John T.

2010-01-01

Objective To determine whether an activity monitor (AM) could be used to detect changes in activity in dogs with osteoarthritis treated with carprofen or a placebo. Design Randomized controlled trial. Animals 70 dogs with no clinically important abnormalities other than osteoarthritis for which they were not currently being treated. Procedures Dogs wore an AM continuously for 21 days. On days 8 through 21, the dogs were treated with carprofen (n = 35) or a placebo (35). Total activity counts for days 1 through 7 (baseline) were compared with total activity counts for days 15 through 21 (endpoint). The change in total activity count from baseline to endpoint was assessed within each treatment group as well as between groups. Linear regression analysis was performed to test for an association between treatment and percentage change in activity counts while controlling for other variables. Results For placebo-treated dogs, median baseline total activity count was not significantly different from median endpoint total activity count (1,378,408 vs 1,310,112, respectively). For dogs receiving carprofen, there was a significant increase in median activity count from baseline to endpoint (1,276,427 vs 1,374,133). When age and baseline activity counts were controlled for, dogs in the carpofen-treated group had a 20% increase in activity counts, compared with placebo-treated dogs (95% confidence interval, 10% to 26%). Conclusions and Clinical Relevance Results suggested that the AM used in the present study may be a valid outcome assessment tool for documenting improved activity associated with treatment in dogs with osteoarthritis. PMID:20590496

Recent changes in ecologically-relevant streamflows in North America

NASA Astrophysics Data System (ADS)

Ficklin, D. L.; Abatzoglou, J. T.; Knouft, J.; Robeson, S. M.

2017-12-01

The streamflow regime is a primary regulator of the composition and functioning of freshwater ecosystems. Growth, behavior, and/or reproduction of most freshwater organisms are influenced in some way by the amount of water, including high and low flows, and seasonal fluctuations in water availability in a particular habitat. This work examines trends in ecologically-relevant measures of streamflows from 1980-2015 for over 3,000 streamflow gauges located throughout Canada and United States. Specifically, we examine trends in water year mean flow and variability, as well as trends in high (95th and 99th percentile), low (1st and 5th percentile), and 7- and 3-day maximum and minimum streamflows. The results indicate a clear regional delineation of significant increases of ecologically-relevant streamflows in the northern Central Plains/south-central Canada, upper Midwest (except Michigan and Wisconsin) and northeastern United States/southeastern Canada, while significant decreases are found throughout the southeastern and southwestern United States. The regional agreement between streamflow trends in regulated and unregulated watersheds indicate a widespread climatic influence that is not masked by human alteration of streamflows. We explore the degree to which climate factors explain both interannual variability and observed trends in streamflow to better elucidate the role of top-down climate drivers versus bottom-up land surface drivers on recent trends in ecologically-relevant streamflow. We also explore how these changes in streamflow are affecting water quality such as water temperature and sediment concentration. This type of analysis will aid in highlighting streamflow regions in the United States that are currently sensitive to changes in climate, but may also aid in understanding which regions may be sensitive to future climatic changes.

Colony impact of pesticide-induced sublethal effects on honeybee workers: A simulation study using BEEHAVE.

PubMed

Thorbek, Pernille; Campbell, Peter J; Thompson, Helen M

2017-03-01

Research on neonicotinoids and honeybees have changed focus from direct mortality to sublethal effects. In the present study, a published honeybee model, BEEHAVE, is used to compare induced colony level impact of pesticides including direct mortality, poor brood care, disorientation, and increased handling time in oilseed rape and sunflower crops. Actual effects on individual bees will depend on exposure concentrations, but in the present study large effects were enforced. In oilseed rape, poor brood care had the largest colony impact, because it created a bottleneck for spring build-up of the workforce, and colony impact for all effect types peaked 1 mo after exposure ceased. In sunflower, the later exposure changed the response so colony impact peaked during exposure, and the bottleneck was honey store build-up. In all scenarios, good forage mitigated effects substantially. It is concluded that field studies should continue at least 1 mo after exposure to ensure detection of ecologically relevant sublethal effects. The results indicated that even if a sublethal effect is difficult to detect in the field, subsequent ecologically relevant colony level impacts would be clear if studies are continued for 1 mo after exposure. Guidance for regulatory studies recommends extended observation periods, and published field studies already use extended observation periods, so it is concluded that current methods are adequate for detecting ecologically relevant sublethal effects. Although published laboratory and semifield studies conducted under controlled exposure conditions suggest that sublethal effects may occur, published field studies with neonicotinoid seed treatments, naturally foraging bees, and extended observation periods do not report colony-level effects, suggesting that in these studies no ecologically relevant sublethal effects occurred. Environ Toxicol Chem 2017;36:831-840. © 2016 SETAC. © 2016 SETAC.

Adding a landscape ecology perspective to conservation and management planning

Treesearch

Kathryn E. Freemark; John R. Probst; John B. Dunning; Salllie J. Hejl

1993-01-01

We briefly review concepts in landscape ecology and discuss their relevance to the conservation and management of neotropical migrant landbirds. We then integrate a landscape perspective into a spatially-hierarchical framework for conservation and management planning for neotropical migrant landbirds (and other biota). The framework outlines a comprehensive approach by...

Passive monitoring techniques for evaluating atmospheric ozone and nitrogen exposure and deposition to California ecosystems

Treesearch

Mark E. Fenn; Andrzej Bytnerowicz; Susan L. Schilling

2018-01-01

Measuring the exposure of ecosystems to ecologically relevant pollutants is needed for evaluating ecosystem effects and to identify regions and resources at risk. In California, ozone (O3) and nitrogen (N) pollutants are of greatest concern for ecological effects. "Passive" monitoring methods have been developed to obtain spatially...

The ecology of forest insect invasions and advances in their management

Treesearch

Eckehard G. Brockerhoff; Andrew M. Liebhold; Herv& #233; Jactel

2006-01-01

Invasions by nonindigenous forest insects can have spectacular effects on the biodiversity, ecology, and economy of affected areas. This introduction explores several critical issues that are generally relevant to invasions by forest insects to provide an extended background for this special issue of the Canadian Journal of Forest Research and...

Transformative Sustainability: Learning from Ecological Systems and Indigenous Wisdom

ERIC Educational Resources Information Center

Burns, Heather L.

2015-01-01

Sustainability is becoming increasingly relevant in higher education, as the need to address complex cultural and ecological problems intensifies. How sustainability is taught has a profound influence on the kind of learning that takes place and the impact it has in the world. Sustainability pedagogy is offered as a tool for creating…

Cross-system comparisons elucidate disturbance complexities and generalities

Treesearch

Debra P.C. Peters; Ariel E. Lugo; F. Stuart Chapin; Steward T.A. Pickett; Michael Duniway; Adrian V. Rocha; Frederick J. Swanson; Christine Laney; Julia Jones

2011-01-01

Given that ecological effects of disturbance have been extensively studied in many ecosystems, it is surprising that few quantitative syntheses across diverse ecosystems have been conducted. Multi-system studies tend to be qualitative because they focus on disturbance types that are difficult to measure in an ecologically relevant way. In addition, synthesis of...

Ecological and Developmental Issues in the Practice of Educational Psychology

ERIC Educational Resources Information Center

Bowler, Josephine

2005-01-01

This conceptual article examines what is meant by the term "ecological-contextual" in relation to the assessment of children's needs. Revisiting the discipline of ethology, the article applies the construct of niche to the human species, including examples from children's experiences to validate the relevance of this link. Issues of…

After 100 years, is coevolution relevant?

Treesearch

Geral I. McDonald

2011-01-01

On the 100th anniversary of the introduction of Cronartium ribicola into western North America, it is fitting to assess the philosophical foundation of plant pathology and forest ecology. We should ask whether this foundation provides sufficient understanding of blister rust, other diseases of North American forests, and general forest ecology to insure the application...

Patient-reported urinary incontinence after radiotherapy for prostate cancer: Quantifying the dose-effect.

PubMed

Cozzarini, Cesare; Rancati, Tiziana; Palorini, Federica; Avuzzi, Barbara; Garibaldi, Elisabetta; Balestrini, Damiano; Cante, Domenico; Munoz, Fernando; Franco, Pierfrancesco; Girelli, Giuseppe; Sini, Carla; Vavassori, Vittorio; Valdagni, Riccardo; Fiorino, Claudio

2017-10-01

Urinary incontinence following radiotherapy (RT) for prostate cancer (PCa) has a relevant impact on patient's quality of life. The aim of the study was to assess the unknown dose-effect relationship for late patient-reported urinary incontinence (LPRUI). Patients were enrolled within the multi-centric study DUE01. Clinical and dosimetry data including the prescribed 2Gy equivalent dose (EQD2) were prospectively collected. LPRUI was evaluated through the ICIQ-SF questionnaire filled in by the patients at RT start/end and therefore every 6months. Patients were treated with conventional (74-80Gy, 1.8-2Gy/fr) or moderately hypo-fractionated RT (65-75.2Gy, 2.2-2.7Gy/fr) in 5 fractions/week with intensity-modulated radiotherapy. Six different end-points of 3-year LPRUI, including or not patient's perception (respectively, subjective and objective end-points), were considered. Multivariable logistic models were developed for each end-point. Data of 298 patients were analyzed. The incidence of the most severe end-point (ICIQ-SF>12) was 5.1%. EQD2 calculated with alpha-beta=0.8Gy showed the best performance in fitting data: the risk of LPRUI markedly increased for EQD2>80Gy. Previous abdominal/pelvic surgery and previous TURP were the clinical factors more significantly predictive of LPRUI. Models showed excellent performances in terms of goodness-of-fit and calibration, confirmed by bootstrap-based internal validation. When included in the analyses, baseline symptoms were a major predictor for 5 out of six end-points. LPRUI after RT for PCa dramatically depends on EQD2 and few clinical factors. Results are consistent with a larger than expected impact of moderate hypo-fractionation on the risk of LPRUI. As expected, baseline symptoms, as captured by ICIQ-SF, are associated to an increased risk of LPRUI. Copyright © 2017 Elsevier B.V. All rights reserved.

Toxicity of tributyltin (TBT) to the freshwater planarian Schmidtea mediterranea.

PubMed

Ofoegbu, Pearl U; Simão, Fátima C P; Cruz, Andreia; Mendo, Sónia; Soares, Amadeu M V M; Pestana, João L T

2016-04-01

The freshwater planarian Schmidtea mediterranea, one of the best characterized animal models for regeneration research and developmental biology, is being recognised as a useful species for ecotoxicological studies. Sensitive endpoints related to planarians' behaviour and regeneration can be easily evaluated after exposure to environmental stressors. In this work the sensitivity of S. mediterranea to a gradient of environmentally relevant concentrations of TBT was studied using multiple endpoints like survival, locomotion, head regeneration and DNA damage. In addition, a feeding assay based on planarian's predatory behaviour was performed. Results indicated that TBT is toxic to planarians with LC50's of 1.87 μg L(-1) Sn and 1.31 μg L(-1) Sn at 48 h and 96 h of exposure respectively. Sub-lethal exposures to TBT significantly reduced locomotion and feeding, delayed head regeneration and caused DNA damage in planarians. The behavioural endpoints (feeding and locomotion) and head regeneration were the most sensitive parameters followed by DNA damage. Similar to other aquatic model organisms, S. mediterranea showed high sensitivity towards TBT exposure. Based on our results, and though further research is required concerning their sensitivity to other pollutants, the use of freshwater planarians as a model species in ecotoxicology is discussed. Copyright © 2016. Published by Elsevier Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Efroymson, Rebecca Ann; Peterson, Mark J; Jones, Daniel Steven

An ecological risk assessment was conducted at Yuma Proving Ground, Arizona, as a demonstration of the Military Ecological Risk Assessment Framework (MERAF). The focus of the assessment was a testing program at Cibola Range, which involved an Apache Longbow helicopter firing Hellfire missiles at moving targets, i.e., M60-A1 tanks. The problem formulation for the assessment included conceptual models for three component activities of the test, helicopter overflight, missile firing, and tracked vehicle movement, and two ecological endpoint entities, woody desert wash communities and desert mule deer (Odocoileus hemionus crooki) populations. An activity-specific risk assessment framework was available to provide guidancemore » for assessing risks associated with aircraft overflights. Key environmental features of the study area include barren desert pavement and tree-lined desert washes. The primary stressors associated with helicopter overflights were sound and the view of the aircraft. The primary stressor associated with Hellfire missile firing was sound. The principal stressor associated with tracked vehicle movement was soil disturbance, and a resulting, secondary stressor was hydrological change. Water loss to washes and wash vegetation was expected to result from increased ponding, infiltrationand/or evaporation associated with disturbances to desert pavement. A plan for estimating integrated risks from the three military activities was included in the problem formulation.« less

A Practical Probabilistic Graphical Modeling Tool for Weighing ...

EPA Pesticide Factsheets

Past weight-of-evidence frameworks for adverse ecological effects have provided soft-scoring procedures for judgments based on the quality and measured attributes of evidence. Here, we provide a flexible probabilistic structure for weighing and integrating lines of evidence for ecological risk determinations. Probabilistic approaches can provide both a quantitative weighing of lines of evidence and methods for evaluating risk and uncertainty. The current modeling structure wasdeveloped for propagating uncertainties in measured endpoints and their influence on the plausibility of adverse effects. To illustrate the approach, we apply the model framework to the sediment quality triad using example lines of evidence for sediment chemistry measurements, bioassay results, and in situ infauna diversity of benthic communities using a simplified hypothetical case study. We then combine the three lines evidence and evaluate sensitivity to the input parameters, and show how uncertainties are propagated and how additional information can be incorporated to rapidly update the probability of impacts. The developed network model can be expanded to accommodate additional lines of evidence, variables and states of importance, and different types of uncertainties in the lines of evidence including spatial and temporal as well as measurement errors. We provide a flexible Bayesian network structure for weighing and integrating lines of evidence for ecological risk determinations

Monitoring and assessment of water health quality in the Tajan River, Iran using physicochemical, fish and macroinvertebrates indices.

PubMed

Aazami, Jaber; Esmaili-Sari, Abbas; Abdoli, Asghar; Sohrabi, Hormoz; Van den Brink, Paul J

2015-01-01

Nowadays, aquatic organisms are used as bio-indicators to assess ecological water quality in western regions, but have hardly been used in an Iranian context. We, therefore, evaluated the suitability of several indices to assess the water quality for an Iranian case study. Measured data on biotic (fish and macroinvertebrates) and abiotic elements (28 physicochemical and habitat parameters), were used to calculate six indices for assessment of water quality and the impact of human activities in the Tajan river, Iran. GIS, uni- and multivariate statistics were used to assess the correlations between biological and environmental endpoints. The results showed that ecological condition and water quality were reduced from up- to downstream. The reduced water quality was revealed by the biotic indices better than the abiotic ones which were linked to a variety of ecological water quality scales. The fish index showed a strong relationship with long-term database of physicochemical parameters (12 years (94%)), whereas macroinvertebrates index is more correlated with short-term data (76%). Meanwhile, the biotic and abiotic elements in this study were also classified well by PCA. Pulp and wood plants and sand mining are indicated to have the most negative effects on the river ecosystem.

A framework for predicting impacts on ecosystem services from (sub)organismal responses to chemicals.

PubMed

Forbes, Valery E; Salice, Chris J; Birnir, Bjorn; Bruins, Randy J F; Calow, Peter; Ducrot, Virginie; Galic, Nika; Garber, Kristina; Harvey, Bret C; Jager, Henriette; Kanarek, Andrew; Pastorok, Robert; Railsback, Steve F; Rebarber, Richard; Thorbek, Pernille

2017-04-01

Protection of ecosystem services is increasingly emphasized as a risk-assessment goal, but there are wide gaps between current ecological risk-assessment endpoints and potential effects on services provided by ecosystems. The authors present a framework that links common ecotoxicological endpoints to chemical impacts on populations and communities and the ecosystem services that they provide. This framework builds on considerable advances in mechanistic effects models designed to span multiple levels of biological organization and account for various types of biological interactions and feedbacks. For illustration, the authors introduce 2 case studies that employ well-developed and validated mechanistic effects models: the inSTREAM individual-based model for fish populations and the AQUATOX ecosystem model. They also show how dynamic energy budget theory can provide a common currency for interpreting organism-level toxicity. They suggest that a framework based on mechanistic models that predict impacts on ecosystem services resulting from chemical exposure, combined with economic valuation, can provide a useful approach for informing environmental management. The authors highlight the potential benefits of using this framework as well as the challenges that will need to be addressed in future work. Environ Toxicol Chem 2017;36:845-859. © 2017 SETAC. © 2017 SETAC.

Evaluating the toxic effects of three priority hazardous and noxious substances (HNS) to rotifer Brachionus plicatilis.

PubMed

Zheng, Lei; Pan, Luqing; Lin, Pengfei; Miao, Jingjing; Wang, Xiufen; Lin, Yufei; Wu, Jiangyue

2017-12-01

Hazardous and noxious substances (HNS) spill in the marine environment is an issue of growing concern, and it will mostly continue to do so in the future owing to the increase of high chemical traffic. Nevertheless, the effects of HNS spill on marine environment, especially on aquatic organisms are unclear. Consequently, it is emergent to provide valuable information for the toxicities to marine biota caused by HNS spill. Accordingly, the acute toxicity of three preferential HNS and sub-lethal effects of acrylonitrile on Brachionus plicatilis were evaluated. The median lethal concentration (LC 50 ) at 24 h were 47.2 mg acrylonitrile L -1 , 276.9 mg styrene L -1 , and 488.3 mg p-xylene L -1 , respectively. Sub-lethal toxicity effects of acrylonitrile on feeding behavior, development, and reproduction parameters of B. plicatilis were also evaluated. Results demonstrated that rates of filtration and ingestion were significantly reduced at 2.0, 4.0, and 8.0 mg L -1 of acrylonitrile. Additionally, reproductive period, fecundity, and life span were significantly decreased at high acrylonitrile concentrations. Conversely, juvenile period was significantly increased at the highest two doses and no effects were observed on embryonic development and post-reproductive period. Meanwhile, we found that ingestion rate decline could be a good predictor of reproduction toxicity in B. plicatilis and ecologically relevant endpoint for toxicity assessment. These data will be useful to assess and deal with marine HNS spillages.

Ecotoxicological assessment of antibiotics: A call for improved consideration of microorganisms.

PubMed

Brandt, Kristian K; Amézquita, Alejandro; Backhaus, Thomas; Boxall, Alistair; Coors, Anja; Heberer, Thomas; Lawrence, John R; Lazorchak, James; Schönfeld, Jens; Snape, Jason R; Zhu, Yong-Guan; Topp, Edward

2015-12-01

Antibiotics play a pivotal role in the management of infectious disease in humans, companion animals, livestock, and aquaculture operations at a global scale. Antibiotics are produced, consumed, and released into the environment at an unprecedented scale causing concern that the presence of antibiotic residues may adversely impact aquatic and terrestrial ecosystems. Here we critically review the ecotoxicological assessment of antibiotics as related to environmental risk assessment (ERA). We initially discuss the need for more specific protection goals based on the ecosystem service concept, and suggest that the ERA of antibiotics, through the application of a mode of toxic action approach, should make more use of ecotoxicological endpoints targeting microorganisms (especially bacteria) and microbial communities. Key ecosystem services provided by microorganisms and associated ecosystem service-providing units (e.g. taxa or functional groups) are identified. Approaches currently available for elucidating ecotoxicological effects on microorganisms are reviewed in detail and we conclude that microbial community-based tests should be used to complement single-species tests to offer more targeted protection of key ecosystem services. Specifically, we propose that ecotoxicological tests should not only assess microbial community function, but also microbial diversity (‘species’ richness) and antibiotic susceptibility. Promising areas for future basic and applied research of relevance to ERA are highlighted throughout the text. In this regard, the most fundamental knowledge gaps probably relate to our rudimentary understanding of the ecological roles of antibiotics in nature and possible adverse effects of environmental pollution with subinhibitory levels of antibiotics.

Classifying the evolutionary and ecological features of neoplasms.

PubMed

Maley, Carlo C; Aktipis, Athena; Graham, Trevor A; Sottoriva, Andrea; Boddy, Amy M; Janiszewska, Michalina; Silva, Ariosto S; Gerlinger, Marco; Yuan, Yinyin; Pienta, Kenneth J; Anderson, Karen S; Gatenby, Robert; Swanton, Charles; Posada, David; Wu, Chung-I; Schiffman, Joshua D; Hwang, E Shelley; Polyak, Kornelia; Anderson, Alexander R A; Brown, Joel S; Greaves, Mel; Shibata, Darryl

2017-10-01

Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient's tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research.

Beyond exposure, sensitivity and adaptive capacity: A response based ecological framework to assess species climate change vulnerability

USGS Publications Warehouse

Fortini, Lucas B.; Schubert, Olivia

2017-01-01

As the impacts of global climate change on species are increasingly evident, there is a clear need to adapt conservation efforts worldwide. Species vulnerability assessments (VAs) are increasingly used to summarize all relevant information to determine a species’ potential vulnerability to climate change and are frequently the first step in informing climate adaptation efforts. VAs commonly integrate multiple sources of information by utilizing a framework that distinguishes factors relevant to species exposure, sensitivity, and adaptive capacity. However, this framework was originally developed for human systems, and its use to evaluate species vulnerability has serious practical and theoretical limitations. By instead defining vulnerability as the degree to which a species is unable to exhibit any of the responses necessary for persistence under climate change (i.e., toleration of projected changes, migration to new climate-compatible areas, enduring in microrefugia, and evolutionary adaptation), we can bring VAs into the realm of ecological science without applying borrowed abstract concepts that have consistently challenged species-centric research and management. This response-based framework to assess species vulnerability to climate change allows better integration of relevant ecological data and past research, yielding results with much clearer implications for conservation and research prioritization.

Ecological Relevance Determines Task Priority in Older Adults' Multitasking.

PubMed

Doumas, Michail; Krampe, Ralf Th

2015-05-01

Multitasking is a challenging aspect of human behavior, especially if the concurrently performed tasks are different in nature. Several studies demonstrated pronounced performance decrements (dual-task costs) in older adults for combinations of cognitive and motor tasks. However, patterns of costs among component tasks differed across studies and reasons for participants' resource allocation strategies remained elusive. We investigated young and older adults' multitasking of a working memory task and two sensorimotor tasks, one with low (finger force control) and one with high ecological relevance (postural control). The tasks were performed in single-, dual-, and triple-task contexts. Working memory accuracy was reduced in dual-task contexts with either sensorimotor task and deteriorated further under triple-task conditions. Postural and force performance deteriorated with age and task difficulty in dual-task contexts. However, in the triple-task context with its maximum resource demands, older adults prioritized postural control over both force control and memory. Our results identify ecological relevance as the key factor in older adults' multitasking. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Towards understanding human ecology in nursing practice: a concept analysis].

PubMed

Huynh, Truc; Alderson, Marie

2010-06-01

Human ecology is an umbrella concept encompassing several social, physical, and cultural elements existing in the individual's external environment. The pragmatic utility method was used to analyze the "human ecology" concept in order to ascertain the conceptual fit with nursing epistemology and to promote its use by nurses in clinical practice. Relevant articles for the review were retrieved from the MEDLINE, CINAHL, PsycINFO, and CSA databases using the terms "human ecology," "environment," "nursing," and "ecology." Data analysis revealed that human ecology is perceived as a theoretical perspective designating a complex, multilayered, and multidimensional system, one that comprises individuals and their reciprocal interactions with their global environments and the subsequent impact of these interactions upon their health. Human ecology preconditions include the individuals, their environments, and their transactions. Attributes of this concept encompass the characteristics of an open system (e.g., interdependence, reciprocal).

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures

USGS Publications Warehouse

Kunz, James L.; Ingersoll, Christopher G.; Smalling, Kelly; Elskus, Adria; Kuivila, Kathryn

2017-01-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubiaand L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. aztecareproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;9999:1–8. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Integrated risk and recovery monitoring of ecosystem restorations on contaminated sites

USGS Publications Warehouse

Hooper, Michael J.; Glomb, Stephen J.; Harper, David; Hoelzle, Timothy B.; McIntosh, Lisa M.; Mulligan, David R.

2016-01-01

Ecological restorations of contaminated sites balance the human and ecological risks of residual contamination with the benefits of ecological recovery and the return of lost ecological function and ecosystem services. Risk and recovery are interrelated dynamic conditions, changing as remediation and restoration activities progress through implementation into long-term management and ecosystem maturation. Monitoring restoration progress provides data critical to minimizing residual contaminant risk and uncertainty, while measuring ecological advancement toward recovery goals. Effective monitoring plans are designed concurrently with restoration plan development and implementation and are focused on assessing the effectiveness of activities performed in support of restoration goals for the site. Physical, chemical, and biotic measures characterize progress toward desired structural and functional ecosystem components of the goals. Structural metrics, linked to ecosystem functions and services, inform restoration practitioners of work plan modifications or more substantial adaptive management actions necessary to maintain desired recovery. Monitoring frequency, duration, and scale depend on specific attributes and goals of the restoration project. Often tied to restoration milestones, critical assessment of monitoring metrics ensures attainment of risk minimization and ecosystem recovery. Finally, interpretation and communication of monitoring findings inform and engage regulators, other stakeholders, the scientific community, and the public. Because restoration activities will likely cease before full ecosystem recovery, monitoring endpoints should demonstrate risk reduction and a successional trajectory toward the condition established in the restoration goals. A detailed assessment of the completed project's achievements, as well as unrealized objectives, attained through project monitoring, will determine if contaminant risk has been minimized, if injured resources have recovered, and if ecosystem services have been returned. Such retrospective analysis will allow better planning for future restoration goals and strengthen the evidence base for quantifying injuries and damages at other sites in the future.

Climate change as an ecosystem architect: implications to rare plant ecology, conservation, and restoration

Treesearch

Constance I. Millar

2003-01-01

Recent advances in earth system sciences have revealed significant new information relevant to rare plant ecology and conservation. Analysis of climate change at high resolution with new and precise proxies of paleotemperatures reveals a picture over the past two million years of oscillatory climate change operating simultaneously at multiple timescales. Low-frequency...

Responsive Classroom Ecologies: Supporting Student Inquiry and Rhetorical Awareness in College Writing Courses

ERIC Educational Resources Information Center

Jankens, Adrienne

2014-01-01

This dissertation describes and analyzes the work of a semester-long teacher research study of inquiry-based and reflective teaching and learning strategies and their impact on students' preparation for future learning. I explore relevant scholarship on knowledge transfer, classroom ecologies, and student agency to set the stage for a discussion…

Process-based models are required to manage ecological systems in a changing world

Treesearch

K. Cuddington; M.-J. Fortin; L.R. Gerber; A. Hastings; A. Liebhold; M. OConnor; C. Ray

2013-01-01

Several modeling approaches can be used to guide management decisions. However, some approaches are better fitted than others to address the problem of prediction under global change. Process-based models, which are based on a theoretical understanding of relevant ecological processes, provide a useful framework to incorporate specific responses to altered...

An integrated remote sensing approach for identifying ecological range sites. [parker mountain

NASA Technical Reports Server (NTRS)

Jaynes, R. A.

1983-01-01

A model approach for identifying ecological range sites was applied to high elevation sagebrush-dominated rangelands on Parker Mountain, in south-central Utah. The approach utilizes map information derived from both high altitude color infrared photography and LANDSAT digital data, integrated with soils, geological, and precipitation maps. Identification of the ecological range site for a given area requires an evaluation of all relevant environmental factors which combine to give that site the potential to produce characteristic types and amounts of vegetation. A table is presented which allows the user to determine ecological range site based upon an integrated use of the maps which were prepared. The advantages of identifying ecological range sites through an integrated photo interpretation/LANDSAT analysis are discussed.

TopFed: TCGA tailored federated query processing and linking to LOD.

PubMed

Saleem, Muhammad; Padmanabhuni, Shanmukha S; Ngomo, Axel-Cyrille Ngonga; Iqbal, Aftab; Almeida, Jonas S; Decker, Stefan; Deus, Helena F

2014-01-01

The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to catalogue genetic mutations responsible for cancer using genome analysis techniques. One of the aims of this project is to create a comprehensive and open repository of cancer related molecular analysis, to be exploited by bioinformaticians towards advancing cancer knowledge. However, devising bioinformatics applications to analyse such large dataset is still challenging, as it often requires downloading large archives and parsing the relevant text files. Therefore, it is making it difficult to enable virtual data integration in order to collect the critical co-variates necessary for analysis. We address these issues by transforming the TCGA data into the Semantic Web standard Resource Description Format (RDF), link it to relevant datasets in the Linked Open Data (LOD) cloud and further propose an efficient data distribution strategy to host the resulting 20.4 billion triples data via several SPARQL endpoints. Having the TCGA data distributed across multiple SPARQL endpoints, we enable biomedical scientists to query and retrieve information from these SPARQL endpoints by proposing a TCGA tailored federated SPARQL query processing engine named TopFed. We compare TopFed with a well established federation engine FedX in terms of source selection and query execution time by using 10 different federated SPARQL queries with varying requirements. Our evaluation results show that TopFed selects on average less than half of the sources (with 100% recall) with query execution time equal to one third to that of FedX. With TopFed, we aim to offer biomedical scientists a single-point-of-access through which distributed TCGA data can be accessed in unison. We believe the proposed system can greatly help researchers in the biomedical domain to carry out their research effectively with TCGA as the amount and diversity of data exceeds the ability of local resources to handle its retrieval and parsing.

Factors Associated With Major Bleeding Events

PubMed Central

Goodman, Shaun G.; Wojdyla, Daniel M.; Piccini, Jonathan P.; White, Harvey D.; Paolini, John F.; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Patel, Manesh R.; Sherwood, Matthew W.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Breithardt, Gunter; Fox, Keith A. A.; Califf, Robert M.

2014-01-01

Objectives This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). Background The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. Methods The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. Results The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. Conclusions Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767) PMID:24315894

Nevada Applied Ecology Information Center: a review of technical information support provided to the Nevada Applied Ecology Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fore, C.S.; Pfuderer, H.A.

The Nevada Applied Ecology Information Center (NAEIC) was established in January 1972 to serve the needs of the Nevada Applied Ecology Group (NAEG) by identifying, collecting, analyzing, and disseminating technical information relevant to NAEG programs. Since its inception, the NAEIC has been active in providing specialized information support to NAEG staff in the following research areas: (1) environmental aspects of the transuranics; (2) historic literature (pre-1962) on plutonium and uranium; (3) cleanup and treatment of radioactively contaminated land; (4) bioenvironmental aspects of europium and rhodium; (5) NAEG contractor reports; and (6) uptake of radioactivity by food crops.

[The Probabilistic Efficiency Frontier: A Value Assessment of Treatment Options in Hepatitis C].

PubMed

Mühlbacher, Axel C; Sadler, Andrew

2017-06-19

Background The German Institute for Quality and Efficiency in Health Care (IQWiG) recommends the concept of the efficiency frontier to assess health care interventions. The efficiency frontier supports regulatory decisions on reimbursement prices for the appropriate allocation of health care resources. Until today this cost-benefit assessment framework has only been applied on the basis of individual patient-relevant endpoints. This contradicts the reality of a multi-dimensional patient benefit. Objective The objective of this study was to illustrate the operationalization of multi-dimensional benefit considering the uncertainty in clinical effects and preference data in order to calculate the efficiency of different treatment options for hepatitis C (HCV). This case study shows how methodological challenges could be overcome in order to use the efficiency frontier for economic analysis and health care decision-making. Method The operationalization of patient benefit was carried out on several patient-relevant endpoints. Preference data from a discrete choice experiment (DCE) study and clinical data based on clinical trials, which reflected the patient and the clinical perspective, respectively, were used for the aggregation of an overall benefit score. A probabilistic efficiency frontier was constructed in a Monte Carlo simulation with 10000 random draws. Patient-relevant endpoints were modeled with a beta distribution and preference data with a normal distribution. The assessment of overall benefit and costs provided information about the adequacy of the treatment prices. The parameter uncertainty was illustrated by the price-acceptability-curve and the net monetary benefit. Results Based on the clinical and preference data in Germany, the interferon-free treatment options proved to be efficient for the current price level. The interferon-free therapies of the latest generation achieved a positive net cost-benefit. Within the decision model, these therapies showed a maximum overall benefit. Due to their high additional benefit and approved prices, the therapies lie above of the extrapolated efficiency frontier, which suggests that these options have efficient reimbursement prices. Considering uncertainty, even a higher price would have resulted in a positive cost-benefit ratio. Conclusion IQWiG's efficiency frontier was used to assess the value of different treatment options in HCV. This study demonstrates that the probabilistic efficiency frontier, price-acceptability-curve and the net monetary benefit can contribute essential information to reimbursement decisions and price negotiations. © Georg Thieme Verlag KG Stuttgart · New York.

Shared decision-making in antihypertensive therapy: a cluster randomised controlled trial

PubMed Central

2013-01-01

Background Hypertension is one of the key factors causing cardiovascular diseases. A substantial proportion of treated hypertensive patients do not reach recommended target blood pressure values. Shared decision making (SDM) is to enhance the active role of patients. As until now there exists little information on the effects of SDM training in antihypertensive therapy, we tested the effect of an SDM training programme for general practitioners (GPs). Our hypotheses are that this SDM training (1) enhances the participation of patients and (2) leads to an enhanced decrease in blood pressure (BP) values, compared to patients receiving usual care without prior SDM training for GPs. Methods The study was conducted as a cluster randomised controlled trial (cRCT) with GP practices in Southwest Germany. Each GP practice included patients with treated but uncontrolled hypertension and/or with relevant comorbidity. After baseline assessment (T0) GP practices were randomly allocated into an intervention and a control arm. GPs of the intervention group took part in the SDM training. GPs of the control group treated their patients as usual. The intervention was blinded to the patients. Primary endpoints on patient level were (1) change of patients’ perceived participation (SDM-Q-9) and (2) change of systolic BP (24h-mean). Secondary endpoints were changes of (1) diastolic BP (24h-mean), (2) patients’ knowledge about hypertension, (3) adherence (MARS-D), and (4) cardiovascular risk score (CVR). Results In total 1357 patients from 36 general practices were screened for blood pressure control by ambulatory blood pressure monitoring (ABPM). Thereof 1120 patients remained in the study because of uncontrolled (but treated) hypertension and/or a relevant comorbidity. At T0 the intervention group involved 17 GP practices with 552 patients and the control group 19 GP practices with 568 patients. The effectiveness analysis could not demonstrate a significant or relevant effect of the SDM training on any of the endpoints. Conclusion The study hypothesis that the SDM training enhanced patients’ perceived participation and lowered their BP could not be confirmed. Further research is needed to examine the impact of patient participation on the treatment of hypertension in primary care. Trial registration German Clinical Trials Register (DRKS): DRKS00000125 PMID:24024587

The incidence and relevance of site-reported vs. patient-reported angina: insights from the ABSORB II randomized trial comparing Absorb everolimus-eluting bioresorbable scaffold with XIENCE everolimus-eluting metallic stent.

PubMed

Grundeken, Maik J; White, Roseann M; Hernandez, John B; Dudek, Dariusz; Cequier, Angel; Haude, Michael; van Boven, Adrianus J; Piek, Jan J; Helqvist, Steffen; Sabate, Manel; Baumbach, Andreas; Suwannasom, Pannipa; Ishibashi, Yuki; Staehr, Peter; Veldhof, Susan; Cheong, Wai-Fung; de Winter, Robbert J; Garcia-Garcia, Hector M; Wykrzykowska, Joanna J; Onuma, Yoshinobu; Serruys, Patrick W; Chevalier, Bernard

2016-04-01

In the ABSORB II trial, comparing Absorb™ bioresorbable vascular scaffold with metallic XIENCE™ everolimus-eluting stent (EES), a difference was found in site-reported new or worsening angina using adverse event (AE) reporting. However, the clinical relevance of this site-reported angina is unclear. The aim of the present study was therefore to investigate the clinical relevance of site-reported angina by evaluating its relation with cardiac endpoints, cardiovascular resource utilization (including diagnostics and treatment), positive exercise stress tolerance tests (ETTs), and Seattle Angina Questionnaire (SAQ). Site-reported new or worsening angina was captured on cardiac AE forms. There was a wide variation in the total number of days with site-reported angina (overall interquartile range 35-279 days). Patients with site-reported angina showed higher rates of cardiovascular events [including the patient-oriented composite endpoint of all deaths, all myocardial infarctions (MI), or all revascularizations (21.1 vs. 4.2%, P < 0.0001), all MIs (2.3 vs. 0%, P = 0.03), and all revascularizations (21.1 vs. 0.7%, P < 0.0001)], cardiovascular resource utilization (including stress tests, anti-anginal medication, diagnostic angiographies, and hospitalization), and positive ETTs (51.9 vs. 14.9%, P < 0.001), compared with those without site-reported angina. Furthermore, an event-based analysis of the SAQ showed that patients with ongoing angina within the recall period of 4 weeks prior to the SAQ assessment have clinically and statistically significant decrements of >14 points in SAQ scores compared with those with no reported angina. We showed that the site-reported angina through AE reporting may be clinically relevant because of their relation with cardiovascular events (mostly repeat revascularizations), cardiovascular resource utilization, ETT, and SAQ. https://clinicaltrials.gov/ct2/show/NCT01425281; Unique identifier: NCT01425281.

The nitrogen fate beyond the current nutrient mitigation measures: sustainability of an integrated agriculture

NASA Astrophysics Data System (ADS)

Thieu, V.; Billen, G. F.; Garnier, J.; Lancelot, C.; Gypens, N.

2010-12-01

Located in the North-Western Europe the terrestrial continuum that includes the Seine, Somme, and Scheldt River basins offers an interesting example of a transborder territory (France, Belgium, and Netherlands) with high-intensity anthropogenic pressures. It well-illustrates the rapid development of modern agriculture in industrialised countries and the resulting severe alteration of water resources and jeopardising the capacity of rural territories to produce drinking water. The corresponding nutrient loads delivered then into the Southern Bight of the North Sea, strongly affect the ecological functioning of the coastal zone. An integrated ‘river-ocean’ assessment, coupling two deterministic models - the SENEQUE RIVESTRAHLER model simulating nutrient dynamic in the drainage network and the MIRO model describing the ecological functioning coastal ecosystem - points out the relevance of current policy based measures (improvement of waste water treatment) to mitigate phosphorous emissions, while the nitrogen pollution related to agriculture will remain critical despite the implementation of classical management measure (good agricultural practices). Therefore and irrespectively of the current political agenda, a more radical alternative is established, consisting of a generalised shift to an integrated agriculture of all agricultural areas in the three basins, excluding the use of synthetically compounded fertilisers and the importation of livestock feed. Such scenario aims at evaluating whether agriculture, by essence, can conciliate (i) the demand for food and feed by local populations, (ii) a good ecological functioning of aquatic ecosystems and (iii) a balanced nutrient status for the adjacent coastal area. This scenario involves an increased livestock density in the Seine and Somme and a decrease in livestock in the Scheldt basin. It leads to a significant reduction of agricultural production that finally brings the three basins closer to autotrophy/heterotrophy equilibrium, while a persisting requirement of long-distance importation of meat and milk clearly emphasises the unsustainability of the increasing share of animal proteins in the modern human diet. In the more optimistic hypothesis, nitrate concentrations in most of the drainage network would drop below the threshold of 2.25 mgN/l (10 mgNO3/L) which is often considered a threshold for a good ecological status. The excess of nitrogen over silica (with respect to the requirements of marine diatoms) delivered into the coastal zones would be decreased by a factor from 2 to 5, thus strongly reducing, but not entirely eliminating the potential for marine eutrophication. Despite a lack a short-term realism, this alternative could appears - in the line of the ‘adapting mosaic’ defined by the Millenium Ecosystem Assessement - as an end-point situation to be compared when building future nutrient reduction policies and incentive agricultural measures.

Assessment of generalizability, applicability and predictability (GAP) for evaluating external validity in studies of universal family-based prevention of alcohol misuse in young people: systematic methodological review of randomized controlled trials.

PubMed

Fernandez-Hermida, Jose Ramon; Calafat, Amador; Becoña, Elisardo; Tsertsvadze, Alexander; Foxcroft, David R

2012-09-01

To assess external validity characteristics of studies from two Cochrane Systematic Reviews of the effectiveness of universal family-based prevention of alcohol misuse in young people. Two reviewers used an a priori developed external validity rating form and independently assessed three external validity dimensions of generalizability, applicability and predictability (GAP) in randomized controlled trials. The majority (69%) of the included 29 studies were rated 'unclear' on the reporting of sufficient information for judging generalizability from sample to study population. Ten studies (35%) were rated 'unclear' on the reporting of sufficient information for judging applicability to other populations and settings. No study provided an assessment of the validity of the trial end-point measures for subsequent mortality, morbidity, quality of life or other economic or social outcomes. Similarly, no study reported on the validity of surrogate measures using established criteria for assessing surrogate end-points. Studies evaluating the benefits of family-based prevention of alcohol misuse in young people are generally inadequate at reporting information relevant to generalizability of the findings or implications for health or social outcomes. Researchers, study authors, peer reviewers, journal editors and scientific societies should take steps to improve the reporting of information relevant to external validity in prevention trials. © 2012 The Authors. Addiction © 2012 Society for the Study of Addiction.

Priorities for CMV vaccine development

PubMed Central

Krause, Philip R.; Bialek, Stephanie R.; Boppana, Suresh B.; Griffiths, Paul D.; Laughlin, Catherine A.; Ljungman, Per; Mocarski, Edward S.; Pass, Robert F.; Read, Jennifer S.; Schleiss, Mark R.; Plotkin, Stanley A.

2015-01-01

A multidisciplinary meeting addressed priorities related to development of vaccines against cytomegalovirus (CMV), the cause of congenital CMV (cCMV) disease and of serious disease in the immunocompromised. Participants discussed optimal uses of a CMV vaccine, aspects of clinical study design, and the value of additional research. A universal childhood CMV vaccine could potentially rapidly reduce cCMV disease, as infected children are sources of viral transmission to seronegative and seropositive mothers. A vaccine administered to adolescents or adult women could also reduce cCMV disease by making them immune prior to pregnancy. Clinical trials of CMV vaccines in women should evaluate protection against cCMV infection, an essential precursor of cCMV disease, which is a more practical and acceptable endpoint for assessing vaccine effects on maternal-fetal transmission. Clinical trials of vaccines to evaluate prevention of CMV disease in stem cell transplant recipients could use CMV viremia at a level triggering preemptive antiviral therapy as an endpoint, because widespread use of preemptive and prophylactic antivirals has rendered CMV-induced disease too rare to be a practical endpoint for clinical trials. In solid organ transplant patients, CMV-associated disease is sufficiently common for use as a primary endpoint. Additional research to advance CMV vaccine development should include identifying factors that predict fetal loss due to CMV, determining age-specific incidence and transmission rates, defining the mechanism and relative contributions of maternal reactivation and re-infection to cCMV disease, developing assays that can distinguish between reactivation and re-infection in seropositive vaccinees, further defining predictors of sequelae from cCMV infection, and identifying clinically relevant immune response parameters to CMV (including developing validated assays that could assess CMV antibody avidity) that could lead to the establishment of immune correlates of protection. PMID:24129123

Thrombectomy in patients ineligible for iv tPA (THRILL).

PubMed

Bendszus, Martin; Thomalla, Götz; Knauth, Michael; Hacke, Werner; Bonekamp, Susanne; Fiehler, Jens

2015-08-01

A relevant proportion of patients with acute ischemic stroke are ineligible for intravenous thrombolysis with recombinant tissue plasminogen activator. Mechanical thrombectomy offers a treatment alternative for these patients; however, only few data are available on its safety and efficacy. The aim of this study was to compare safety and efficacy of stent retrievers as device class with best medical care alone in acute stroke patients with large intracranial vessel occlusion in the anterior circulation who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator up to eight-hours of symptom onset. 'Thrombectomy in patients ineligible for iv tPA' is a prospective, open-label, blinded end-point, binational (Germany and Austria), two-arm, randomized, controlled, post-market study. Primary end-point is the modified Rankin Score shift analysis 90 days (±14) after stroke. Secondary end-points are excellent neurological outcomes (modified Rankin Score ≤ 1), good neurological outcomes (modified Rankin Score ≤ 2 or National Institutes of Health Stroke Scale improvement ≥ 10), difference between predicted infarct volume and actual core infarct volume (computed tomography or magnetic resonance imaging) at 30 (±6) h post-ictus, successful recanalization (thrombolysis in cerebral infarction score 2b or 3), functional health status 90 (±14) days after stroke (European Quality of Life-5 Dimensions) as well as common safety end-points (adverse event, serious adverse event, symptomatic intracranial haemorrhage at 30 (±6) h, death, or dependency). Whether mechanical thrombectomy in patients with acute ischemic stroke who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator improves clinical outcomes is unclear. 'Thrombectomy in patients ineligible for iv tPA' may change clinical practice by providing evidence of an effective and safe treatment for such patients. © 2015 World Stroke Organization.

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol for a controlled clinical trial developed by consensus of an international study group. Part two: design of the study.

PubMed

Bauhofer, A; Lorenz, W; Stinner, B; Rothmund, M; Koller, M; Sitter, H; Celik, I; Farndon, J R; Fingerhut, A; Hay, J M; Lefering, R; Lorijn, R; Nyström, P O; Schäfer, H; Schein, M; Solomkin, J; Troidl, H; Volk, H D; Wittmann, D H; Wyatt, J

2001-04-01

Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). This part describes the design of the randomised, placebo controlled, double-blinded, single-centre study performed at an university hospital (n = 40 patients for each group). The trial design includes the following elements for a prototype protocol: * The study population is restricted to patients with colorectal cancer, including a left sided resection and an increased perioperative risk (ASA 3 and 4). * Patients are allocated by random to the control or treatment group. * The double blinding strategy of the trial is assessed by psychometric indices. * An endpoint construct with quality of life (EORTC QLQ-C30) and a recovery index (modified Mc Peek index) are used as primary endpoints. Qualitative analysis of clinical relevance of the endpoints is performed by both patients and doctors. * Statistical analysis uses an area under the curve (AUC) model for improvement of quality of life on leaving hospital and two and six months after operation. A confirmatory statistical model with quality of life as the first primary endpoint in the hierarchic test procedure is used. Expectations of patients and surgeons and the negative affect are analysed by social psychological scales. This study design differs from other trials on preoperative prophylaxis and postoperative recovery, and has been developed to try a new concept and avoid previous failures.

Human neuron-astrocyte 3D co-culture-based assay for evaluation of neuroprotective compounds.

PubMed

Terrasso, Ana Paula; Silva, Ana Carina; Filipe, Augusto; Pedroso, Pedro; Ferreira, Ana Lúcia; Alves, Paula Marques; Brito, Catarina

Central nervous system drug development has registered high attrition rates, mainly due to the lack of efficacy of drug candidates, highlighting the low reliability of the models used in early-stage drug development and the need for new in vitro human cell-based models and assays to accurately identify and validate drug candidates. 3D human cell models can include different tissue cell types and represent the spatiotemporal context of the original tissue (co-cultures), allowing the establishment of biologically-relevant cell-cell and cell-extracellular matrix interactions. Nevertheless, exploitation of these 3D models for neuroprotection assessment has been limited due to the lack of data to validate such 3D co-culture approaches. In this work we combined a 3D human neuron-astrocyte co-culture with a cell viability endpoint for the implementation of a novel in vitro neuroprotection assay, over an oxidative insult. Neuroprotection assay robustness and specificity, and the applicability of Presto Blue, MTT and CytoTox-Glo viability assays to the 3D co-culture were evaluated. Presto Blue was the adequate endpoint as it is non-destructive and is a simpler and reliable assay. Semi-automation of the cell viability endpoint was performed, indicating that the assay setup is amenable to be transferred to automated screening platforms. Finally, the neuroprotection assay setup was applied to a series of 36 test compounds and several candidates with higher neuroprotective effect than the positive control, Idebenone, were identified. The robustness and simplicity of the implemented neuroprotection assay with the cell viability endpoint enables the use of more complex and reliable 3D in vitro cell models to identify and validate drug candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

EDTA Chelation Therapy Alone and in Combination with Oral High-Dose Multivitamins and Minerals for Coronary Disease: The Factorial Group Results of the Trial to Assess Chelation Therapy

PubMed Central

Lamas, Gervasio A.; Boineau, Robin; Goertz, Christine; Mark, Daniel B.; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L.; Chappell, L. Terry; Lindblad, Lauren; Lewis, Eldrin F.; Drisko, Jeanne; Lee, Kerry L.

2014-01-01

Background Disodium ethylene diamine tetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. Objective This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes. Methods Double-blind placebo-controlled 2 × 2 factorial multicenter randomized trial of 1708 post-MI patients ≥ 50 years and creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitaminmultimineral mixture or placebo. Primary endpoint was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina. Results Median age was 65 years, 18% female, 94% Caucasian, 37% diabetic, 83% prior coronary revascularization, and 73% on statins. Five-year Kaplan-Meier estimates for the primary endpoint in the chelation + high-dose vitamin group was 31.9%, in the chelation + placebo vitamin group 33.7%, in the placebo infusion + active vitamin group 36.6%, and in the placebo infusions + placebo vitamin group 40.2 %. The reduction in primary endpoint by double active treatment compared with double placebo was significant (HR 0.74, 95% CI (0.57,0.95); p=0.016). In patients with diabetes, the primary endpoint reduction of double active compared with double placebo was more pronounced (HR 0.49, 95% CI (0.33,0.75), p<0.001). Conclusions In stable post- MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance. PMID:24952858

Benchmarking organic micropollutants in wastewater, recycled water and drinking water with in vitro bioassays.

PubMed

Escher, Beate I; Allinson, Mayumi; Altenburger, Rolf; Bain, Peter A; Balaguer, Patrick; Busch, Wibke; Crago, Jordan; Denslow, Nancy D; Dopp, Elke; Hilscherova, Klara; Humpage, Andrew R; Kumar, Anu; Grimaldi, Marina; Jayasinghe, B Sumith; Jarosova, Barbora; Jia, Ai; Makarov, Sergei; Maruya, Keith A; Medvedev, Alex; Mehinto, Alvine C; Mendez, Jamie E; Poulsen, Anita; Prochazka, Erik; Richard, Jessica; Schifferli, Andrea; Schlenk, Daniel; Scholz, Stefan; Shiraishi, Fujio; Snyder, Shane; Su, Guanyong; Tang, Janet Y M; van der Burg, Bart; van der Linden, Sander C; Werner, Inge; Westerheide, Sandy D; Wong, Chris K C; Yang, Min; Yeung, Bonnie H Y; Zhang, Xiaowei; Leusch, Frederic D L

2014-01-01

Thousands of organic micropollutants and their transformation products occur in water. Although often present at low concentrations, individual compounds contribute to mixture effects. Cell-based bioassays that target health-relevant biological endpoints may therefore complement chemical analysis for water quality assessment. The objective of this study was to evaluate cell-based bioassays for their suitability to benchmark water quality and to assess efficacy of water treatment processes. The selected bioassays cover relevant steps in the toxicity pathways including induction of xenobiotic metabolism, specific and reactive modes of toxic action, activation of adaptive stress response pathways and system responses. Twenty laboratories applied 103 unique in vitro bioassays to a common set of 10 water samples collected in Australia, including wastewater treatment plant effluent, two types of recycled water (reverse osmosis and ozonation/activated carbon filtration), stormwater, surface water, and drinking water. Sixty-five bioassays (63%) showed positive results in at least one sample, typically in wastewater treatment plant effluent, and only five (5%) were positive in the control (ultrapure water). Each water type had a characteristic bioanalytical profile with particular groups of toxicity pathways either consistently responsive or not responsive across test systems. The most responsive health-relevant endpoints were related to xenobiotic metabolism (pregnane X and aryl hydrocarbon receptors), hormone-mediated modes of action (mainly related to the estrogen, glucocorticoid, and antiandrogen activities), reactive modes of action (genotoxicity) and adaptive stress response pathway (oxidative stress response). This study has demonstrated that selected cell-based bioassays are suitable to benchmark water quality and it is recommended to use a purpose-tailored panel of bioassays for routine monitoring.

Demonstration of the Military Ecological Risk Assessment Framework (MERAF): Apache Longbow - Hell Missile Test at Yuma Proving Ground

DOE Office of Scientific and Technical Information (OSTI.GOV)

Efroymson, R.A.

2002-05-09

This ecological risk assessment for a testing program at Yuma Proving Ground, Arizona, is a demonstration of the Military Ecological Risk Assessment Framework (MERAF; Suter et al. 2001). The demonstration is intended to illustrate how risk assessment guidance concerning-generic military training and testing activities and guidance concerning a specific type of activity (e.g., low-altitude aircraft overflights) may be implemented at a military installation. MERAF was developed with funding from the Strategic Research and Development Program (SERDP) of the Department of Defense. Novel aspects of MERAF include: (1) the assessment of risks from physical stressors using an ecological risk assessment framework,more » (2) the consideration of contingent or indirect effects of stressors (e.g., population-level effects that are derived from habitat or hydrological changes), (3) the integration of risks associated with different component activities or stressors, (4) the emphasis on quantitative risk estimates and estimates of uncertainty, and (5) the modularity of design, permitting components of the framework to be used in various military risk assessments that include similar activities. The particular subject of this report is the assessment of ecological risks associated with a testing program at Cibola Range of Yuma Proving Ground, Arizona. The program involves an Apache Longbow helicopter firing Hellfire missiles at moving targets, i.e., M60-A1 tanks. Thus, the three component activities of the Apache-Hellfire test were: (1) helicopter overflight, (2) missile firing, and (3) tracked vehicle movement. The demonstration was limited, to two ecological endpoint entities (i.e., potentially susceptible and valued populations or communities): woody desert wash communities and mule deer populations. The core assessment area is composed of about 126 km{sup 2} between the Chocolate and Middle Mountains. The core time of the program is a three-week period, including fourteen days of activity in August of 2000.« less

Establishing a group of endpoints to support collective operations without specifying unique identifiers for any endpoints

DOEpatents

Archer, Charles J.; Blocksom, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanghon

2016-02-02

A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

NetMap: a new tool in support of watershed science and resource management.

Treesearch

L. Benda; D. Miller; K. Andras; P. Bigelow; G. Reeves; D. Michael

2007-01-01

In this paper, we show how application of principles of river ecology can guide use of a comprehensive terrain database within geographic information system (GIS) to facilitate watershed analysis relevant to natural resource management. We present a unique arrangement of a terrain database, GIS, and principles of riverine ecology for the purpose of advancing watershed...

Bayesian Inference: with ecological applications

USGS Publications Warehouse

Link, William A.; Barker, Richard J.

2010-01-01

This text provides a mathematically rigorous yet accessible and engaging introduction to Bayesian inference with relevant examples that will be of interest to biologists working in the fields of ecology, wildlife management and environmental studies as well as students in advanced undergraduate statistics.. This text opens the door to Bayesian inference, taking advantage of modern computational efficiencies and easily accessible software to evaluate complex hierarchical models.

Studying the neurobiology of human social interaction: Making the case for ecological validity.

PubMed

Hogenelst, Koen; Schoevers, Robert A; aan het Rot, Marije

2015-01-01

With this commentary we make the case for an increased focus on the ecological validity of the measures used to assess aspects of human social functioning. Impairments in social functioning are seen in many types of psychopathology, negatively affecting the lives of psychiatric patients and those around them. Yet the neurobiology underlying abnormal social interaction remains unclear. As an example of human social neuroscience research with relevance to biological psychiatry and clinical psychopharmacology, this commentary discusses published experimental studies involving manipulation of the human brain serotonin system that included assessments of social behavior. To date, these studies have mostly been laboratory-based and included computer tasks, observations by others, or single-administration self-report measures. Most laboratory measures used so far inform about the role of serotonin in aspects of social interaction, but the relevance for real-life interaction is often unclear. Few studies have used naturalistic assessments in real life. We suggest several laboratory methods with high ecological validity as well as ecological momentary assessment, which involves intensive repeated measures in naturalistic settings. In sum, this commentary intends to stimulate experimental research on the neurobiology of human social interaction as it occurs in real life.

Using species sensitivity distribution approach to assess the risks of commonly detected agricultural pesticides to Australia's tropical freshwater ecosystems.

PubMed

Pathiratne, Asoka; Kroon, Frederieke J

2016-02-01

To assess the potential impacts of agricultural pesticides on tropical freshwater ecosystems, the present study developed temperature-specific, freshwater species protection concentrations (i.e., ecotoxicity threshold values) for 8 pesticides commonly detected in Australia's tropical freshwaters. Because relevant toxicity data for native tropical freshwater species to assess the ecological risks were mostly absent, scientifically robust toxicity data obtained at ≥20 °C were used for ecologically relevant taxonomic groups representing primary producers and consumers. Species sensitivity distribution (SSD) curves were subsequently generated for predicted chronic exposure using Burrlioz 2.0 software with mixed chronic and converted acute data relevant to exposure conditions at ≥20 °C. Ecotoxicity threshold values for tropical freshwater ecosystem protection were generated for ametryn, atrazine, diuron, metolachlor, and imidacloprid (all moderate reliability), as well as simazine, hexazinone, and tebuthiuron (all low reliability). Using these SSD curves, the retrospective risk assessments for recently reported pesticide concentrations highlight that the herbicides ametryn, atrazine, and diuron are of major concern for ecological health in Australia's tropical freshwater ecosystems. The insecticide imidacloprid also appears to pose an emerging threat to the most sensitive species in tropical freshwater ecosystems. The exposed temperature-specific approach may be applied to develop water quality guideline values for other environmental contaminants detected in tropical freshwater ecosystems until reliable and relevant toxicity data are generated using representative native species. © 2015 SETAC.

Land management in the Anthropocene: Is history still relevant?

USGS Publications Warehouse

Safford, Hugh D.; Betancourt, Julio L.; Hayward, Gregory D.; Wiens, John A.; Regan, Claudia M.

2008-01-01

Ecological restoration, conservation, and land management are often based on comparisons with reference sites or time periods, which are assumed to represent “natural” or “properly functioning” conditions. Such reference conditions can provide a vision of the conservation or management goal and a means to measure progress toward that vision. Although historical ecology has been used successfully to guide resource management in many parts of the world, the continuing relevance of history is now being questioned. Some scientists doubt that lessons from the past can inform management in what may be a dramatically different future, given profound climate change, accelerated land use, and an onslaught of plant and animal invasions.

The ecological competition and grazing reverse the effects of sulfamethoxazole on plankton: a case study on characterizing community-level effect.

PubMed

Wang, Changyou; Liang, Shengkang; Zhang, Yong

2018-04-12

The toxic effects of sulfamethoxazole (SMX) on densities of two algae, Platymonas helgolandica var. tsingtaoensis, Isochrysis galbana, and of a rotifer, Brachionus plicatilis, were tested by the population and community experiments. Two endpoints, the carrying capacity and the densities array of community in steady state (DACS), were used to characterize the toxic effects at a population level and a community one, respectively. The results showed that the carrying capacity of P. helgolandica var. tsingtaoensis and B. plicatilis did not decline significantly in population test when the concentration of SMX was lower than 6.0 mg L -1 and 12.0 mg L -1 , respectively. However, I. galbana was sensitive to SMX and had presented toxic effect at 3.0 mg L -1 . By extrapolation of toxic effect at a population level to a community one, a derived community-NOEC was 3.0 mg L -1 , representing an inference from data of toxic effects at population level. In community experiment, when the customized community was in steady state, the density of I. galbana increased as a whole with SMX concentration in the range of tested concentration (0-144 mg L -1 ), while that of P. helgolandica var. tsingtaoensis assumed the trend of a reversed "v" in this range. Only the density of B. plicatilis decreased with SMX concentration. With the DACS as endpoint, a NOEC for the customized community was determined to be 6.0 mg L -1 . This indicates that interspecific interactions can reverse the toxic effects of SMX on phytoplankton. The DACS was reliable and stable, serving as the endpoints in assessment of the effects of the pollutants on the ecosystems.

An exploration into study design for biomarker identification: issues and recommendations.

PubMed

Hall, Jacqueline A; Brown, Robert; Paul, Jim

2007-01-01

Genomic profiling produces large amounts of data and a challenge remains in identifying relevant biological processes associated with clinical outcome. Many candidate biomarkers have been identified but few have been successfully validated and make an impact clinically. This review focuses on some of the study design issues encountered in data mining for biomarker identification with illustrations of how study design may influence the final results. This includes issues of clinical endpoint use and selection, power, statistical, biological and clinical significance. We give particular attention to study design for the application of supervised clustering methods for identification of gene networks associated with clinical outcome and provide recommendations for future work to increase the success of identification of clinically relevant biomarkers.

Problem formulation in the environmental risk assessment for genetically modified plants

PubMed Central

Wolt, Jeffrey D.; Keese, Paul; Raybould, Alan; Burachik, Moisés; Gray, Alan; Olin, Stephen S.; Schiemann, Joachim; Sears, Mark; Wu, Felicia

2009-01-01

Problem formulation is the first step in environmental risk assessment (ERA) where policy goals, scope, assessment endpoints, and methodology are distilled to an explicitly stated problem and approach for analysis. The consistency and utility of ERAs for genetically modified (GM) plants can be improved through rigorous problem formulation (PF), producing an analysis plan that describes relevant exposure scenarios and the potential consequences of these scenarios. A properly executed PF assures the relevance of ERA outcomes for decision-making. Adopting a harmonized approach to problem formulation should bring about greater uniformity in the ERA process for GM plants among regulatory regimes globally. This paper is the product of an international expert group convened by the International Life Sciences Institute (ILSI) Research Foundation. PMID:19757133

Impedance-based cellular assay technologies: recent advances, future promise.

PubMed

McGuinness, Ryan

2007-10-01

Cell-based assays are continuing to grow in importance in the drug discovery workflow. Their early introduction holds the promise of limiting attrition in the later, more costly phases of the process. This article reviews recent advances in the development of impedance technologies for label-free cell-based assays. These systems are capable of monitoring endogenous receptor activation, and thus generate more physiologically relevant measures of pharmacological endpoints. Primary cells can be investigated as well, thus producing disease relevant information. Label-free assays significantly decrease assay development efforts and avoid many complications inherent in recombinant readout systems. Impedance-based systems have great potential to advance the utility of cell-based assays as they are applied to drug discovery and pharmacology.

US EPA's Ecological Risk Assessment Support Center ...

EPA Pesticide Factsheets

BackgroundThe ERASC provides technical information and addresses scientific questions of concern or interest on topics relevant to ecological risk assessment at hazardous waste sites for EPA's Office of Solid Waste and Emergency Response (OSWER) personnel and the Office of Resource Conservation and Recovery (ORCR) staff. Requests are channeled to ERASC through the Ecological Risk Assessment Forum (ERAF). To assess emerging and complex scientific issues that require expert judgment, the ERASC relies on the expertise of scientists and engineers located throughout EPA's Office of Research and Development (ORD) labs and centers.ResponseERASC develops responses that reflect the state of the science for ecological risk assessment and also provides a communication point for the distribution of the responses to other interested parties. For further information, contact Ecology_ERASC@epa.gov or call 513-569-7940.

Patients as Patches: Ecology and Epidemiology in Healthcare Environments.

PubMed

Lofgren, Eric T; Egizi, Andrea M; Fefferman, Nina H

2016-12-01

The modern healthcare system involves complex interactions among microbes, patients, providers, and the built environment. It represents a unique and challenging setting for control of the emergence and spread of infectious diseases. We examine an extension of the perspectives and methods from ecology (and especially urban ecology) to address these unique issues, and we outline 3 examples: (1) viewing patients as individual microbial ecosystems; (2) the altered ecology of infectious diseases specifically within hospitals; and (3) ecosystem management perspectives for infection surveillance and control. In each of these cases, we explore the accuracy and relevance of analogies to existing urban ecological perspectives, and we demonstrate a few of the potential direct uses of this perspective for altering research into the control of healthcare-associated infections. Infect Control Hosp Epidemiol. 2016;1507-1512.

Classifying the evolutionary and ecological features of neoplasms

PubMed Central

Maley, Carlo C.; Aktipis, Athena; Graham, Trevor A.; Sottoriva, Andrea; Boddy, Amy M.; Janiszewska, Michalina; Silva, Ariosto S.; Gerlinger, Marco; Yuan, Yinyin; Pienta, Kenneth J.; Anderson, Karen S.; Gatenby, Robert; Swanton, Charles; Posada, David; Wu, Chung-I; Schiffman, Joshua D.; Hwang, E. Shelley; Polyak, Kornelia; Anderson, Alexander R. A.; Brown, Joel S.; Greaves, Mel; Shibata, Darryl

2018-01-01

Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient’s tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research. PMID:28912577

Making research relevant? Ecological methods and the ecosystem services framework

NASA Astrophysics Data System (ADS)

Root-Bernstein, Meredith; Jaksic, Fabián. M.

2017-07-01

We examine some unexpected epistemological conflicts that arise at the interfaces between ecological science, the ecosystem services framework, policy, and industry. We use an example from our own research to motivate and illustrate our main arguments, while also reviewing standard approaches to ecological science using the ecosystem services framework. While we agree that the ecosystem services framework has benefits in its industrial applications because it may force economic decision makers to consider a broader range of costs and benefits than they would do otherwise, we find that many alignments of ecology with the ecosystem services framework are asking questions that are irrelevant to real-world applications, and generating data that does not serve real-world applications. We attempt to clarify why these problems arise and how to avoid them. We urge fellow ecologists to reflect on the kind of research that can lead to both scientific advances and applied relevance to society. In our view, traditional empirical approaches at landscape scales or with place-based emphases are necessary to provide applied knowledge for problem solving, which is needed once decision makers identify risks to ecosystem services. We conclude that the ecosystem services framework is a good policy tool when applied to decision-making contexts, but not a good theory either of social valuation or ecological interactions, and should not be treated as one.

The Sphagnome Project: enabling ecological and evolutionary insights through a genus-level sequencing project

DOE PAGES

Weston, David J.; Turetsky, Merritt R.; Johnson, Matthew G.; ...

2017-10-27

Considerable progress has been made in ecological and evolutionary genetics with studies demonstrating how genes underlying plant and microbial traits can influence adaptation and even ‘extend’ to influence community structure and ecosystem level processes. The progress in this area is limited to model systems with deep genetic and genomic resources that often have negligible ecological impact or interest. Therefore, important linkages between genetic adaptations and their consequences at organismal and ecological scales are often lacking. We introduce the Sphagnome Project, which incorporates genomics into a long-running history of Sphagnum research that has documented unparalleled contributions to peatland ecology, carbon sequestration,more » biogeochemistry, microbiome research, niche construction, and ecosystem engineering. The Sphagnome Project encompasses a genus-level sequencing effort that represents a new type of model system driven not only by genetic tractability, but by ecologically relevant questions and hypotheses.« less

Vive la résistance: reviving resistance for 21st century conservation.

PubMed

Nimmo, D G; Mac Nally, R; Cunningham, S C; Haslem, A; Bennett, A F

2015-09-01

Confronted with increasing anthropogenic change, conservation in the 21st century requires a sound understanding of how ecological systems change during disturbance. We highlight the benefits of recognizing two distinct components of change in an ecological unit (i.e., ecosystem, community, population): 'resistance', the ability to withstand disturbance; and 'resilience', the capacity to recover following disturbance. By adopting a 'resistance-resilience' framework, important insights for conservation can be gained into: (i) the key role of resistance in response to persistent disturbance, (ii) the intrinsic attributes of an ecological unit associated with resistance and resilience, (iii) the extrinsic environmental factors that influence resistance and resilience, (iv) mechanisms that confer resistance and resilience, (v) the post-disturbance status of an ecological unit, (vi) the nature of long-term ecological changes, and (vii) policy-relevant ways of communicating the ecological impacts of disturbance processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Sphagnome Project: enabling ecological and evolutionary insights through a genus-level sequencing project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weston, David J.; Turetsky, Merritt R.; Johnson, Matthew G.

Considerable progress has been made in ecological and evolutionary genetics with studies demonstrating how genes underlying plant and microbial traits can influence adaptation and even ‘extend’ to influence community structure and ecosystem level processes. The progress in this area is limited to model systems with deep genetic and genomic resources that often have negligible ecological impact or interest. Therefore, important linkages between genetic adaptations and their consequences at organismal and ecological scales are often lacking. We introduce the Sphagnome Project, which incorporates genomics into a long-running history of Sphagnum research that has documented unparalleled contributions to peatland ecology, carbon sequestration,more » biogeochemistry, microbiome research, niche construction, and ecosystem engineering. The Sphagnome Project encompasses a genus-level sequencing effort that represents a new type of model system driven not only by genetic tractability, but by ecologically relevant questions and hypotheses.« less

The Sphagnome Project: enabling ecological and evolutionary insights through a genus-level sequencing project.

PubMed

Weston, David J; Turetsky, Merritt R; Johnson, Matthew G; Granath, Gustaf; Lindo, Zoë; Belyea, Lisa R; Rice, Steven K; Hanson, David T; Engelhardt, Katharina A M; Schmutz, Jeremy; Dorrepaal, Ellen; Euskirchen, Eugénie S; Stenøien, Hans K; Szövényi, Péter; Jackson, Michelle; Piatkowski, Bryan T; Muchero, Wellington; Norby, Richard J; Kostka, Joel E; Glass, Jennifer B; Rydin, Håkan; Limpens, Juul; Tuittila, Eeva-Stiina; Ullrich, Kristian K; Carrell, Alyssa; Benscoter, Brian W; Chen, Jin-Gui; Oke, Tobi A; Nilsson, Mats B; Ranjan, Priya; Jacobson, Daniel; Lilleskov, Erik A; Clymo, R S; Shaw, A Jonathan

2018-01-01

Considerable progress has been made in ecological and evolutionary genetics with studies demonstrating how genes underlying plant and microbial traits can influence adaptation and even 'extend' to influence community structure and ecosystem level processes. Progress in this area is limited to model systems with deep genetic and genomic resources that often have negligible ecological impact or interest. Thus, important linkages between genetic adaptations and their consequences at organismal and ecological scales are often lacking. Here we introduce the Sphagnome Project, which incorporates genomics into a long-running history of Sphagnum research that has documented unparalleled contributions to peatland ecology, carbon sequestration, biogeochemistry, microbiome research, niche construction, and ecosystem engineering. The Sphagnome Project encompasses a genus-level sequencing effort that represents a new type of model system driven not only by genetic tractability, but by ecologically relevant questions and hypotheses. © 2017 UT-Battelle New Phytologist © 2017 New Phytologist Trust.

Establishing a group of endpoints in a parallel computer

DOEpatents

Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanhong

2016-02-02

A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

Asymmetric interjoint feedback contributes to postural control of redundant multi-link systems

NASA Astrophysics Data System (ADS)

Bunderson, Nathan E.; Ting, Lena H.; Burkholder, Thomas J.

2007-09-01

Maintaining the postural configuration of a limb such as an arm or leg is a fundamental neural control task that involves the coordination of multiple linked body segments. Biological systems are known to use a complex network of inter- and intra-joint feedback mechanisms arising from muscles, spinal reflexes and higher neuronal structures to stabilize the limbs. While previous work has shown that a small amount of asymmetric heterogenic feedback contributes to the behavior of these systems, a satisfactory functional explanation for this non-conservative feedback structure has not been put forth. We hypothesized that an asymmetric multi-joint control strategy would confer both an energetic and stability advantage in maintaining endpoint position of a kinematically redundant system. We tested this hypothesis by using optimal control models incorporating symmetric versus asymmetric feedback with the goal of maintaining the endpoint location of a kinematically redundant, planar limb. Asymmetric feedback improved endpoint control performance of the limb by 16%, reduced energetic cost by 21% and increased interjoint coordination by 40% compared to the symmetric feedback system. The overall effect of the asymmetry was that proximal joint motion resulted in greater torque generation at distal joints than vice versa. The asymmetric organization is consistent with heterogenic stretch reflex gains measured experimentally. We conclude that asymmetric feedback has a functionally relevant role in coordinating redundant degrees of freedom to maintain the position of the hand or foot.

Asymmetric interjoint feedback contributes to postural control of redundant multi-link systems

PubMed Central

Bunderson, Nathan E.; Ting, Lena H.; Burkholder, Thomas J.

2008-01-01

Maintaining the postural configuration of a limb such as an arm or leg is a fundamental neural control task that involves the coordination of multiple linked body segments. Biological systems are known to use a complex network of inter- and intra-joint feedback mechanisms arising from muscles, spinal reflexes, and higher neuronal structures to stabilize the limbs. While previous work has shown that a small amount of asymmetric heterogenic feedback contributes to the behavior of these systems, a satisfactory functional explanation for this nonconservative feedback structure has not been put forth. We hypothesized that an asymmetric multi-joint control strategy would confer both an energetic and stability advantage in maintaining endpoint position of a kinematically redundant system. We tested this hypothesis by using optimal control models incorporating symmetric versus asymmetric feedback with the goal of maintaining the endpoint location of a kinematically redundant, planar limb. Asymmetric feedback improved endpoint control performance of the limb by 16%, reduced energetic cost by 21% and increased interjoint coordination by 40% compared to the symmetric feedback system. The overall effect of the asymmetry was that proximal joint motion resulted in greater torque generation at distal joints than vice versa. The asymmetric organization is consistent with heterogenic stretch reflex gains measured experimentally. We conclude that asymmetric feedback has a functionally relevant role in coordinating redundant degrees of freedom to maintain the position of the hand or foot. PMID:17873426

Derivation of an occupational exposure limit for inorganic borates using a weight of evidence approach.

PubMed

Maier, A; Vincent, M; Hack, E; Nance, P; Ball, W

2014-04-01

Inorganic borates are encountered in many settings worldwide, spurring international efforts to develop exposure guidance (US EPA, 2004; WHO, 2009; ATSDR, 2010) and occupational exposure limits (OEL) (ACGIH, 2005; MAK, 2011). We derived an updated OEL to reflect new data and current international risk assessment frameworks. We assessed toxicity and epidemiology data on inorganic borates to identify relevant adverse effects. International risk assessment frameworks (IPCS, 2005, 2007) were used to evaluate endpoint candidates: reproductive toxicity, developmental toxicity, and sensory irritation. For each endpoint, a preliminary OEL was derived and adjusted based on consideration of toxicokinetics, toxicodynamics, and other uncertainties. Selection of the endpoint point of departures (PODs) is supported by dose-response modeling. Developmental toxicity was the most sensitive systemic effect. An OEL of 1.6mgB/m(3) was estimated for this effect based on a POD of 63mgB/m(3) with an uncertainty factor (UF) of 40. Sensory irritation was considered to be the most sensitive effect for the portal of entry. An OEL of 1.4mgB/m(3) was estimated for this effect based on the identified POD and an UF of 1. An OEL of 1.4mgB/m(3) as an 8-h time-weighted average (TWA) is recommended. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypoglycemia evaluation and reporting in diabetes: Importance for the development of new therapies.

PubMed

Klonoff, David C; Alexander Fleming, G; Muchmore, Douglas B; Frier, Brian M

2017-07-01

Hypoglycemia complicating diabetes therapy is well recognized to be an ever-present threat to patients, their families, providers, payers, and regulators. Despite this being widely acknowledged, the regulatory stance on hypoglycemia as an endpoint in clinical trials to support new product registration has not evolved in any meaningful way since the publication of a position paper by an American Diabetes Association (ADA) Workgroup in 2005. As the impact of hypoglycemia on persons affected by diabetes is of major importance when assessing new treatments, the historical position of regulatory agencies on hypoglycemia is reviewed with respect to product approvals. The purpose of this article is to present proposals for facilitating development of therapies that reduce hypoglycemia risk through (1) development of composite measures of benefit for regulatory endpoints and (2) facilitation of the fulfillment of an unmet clinical need for reducing hypoglycemia. In view of greater comprehension of the effects of hypoglycemia, coupled with improved methodology to assess its frequency, the authors recommend: (1) a numerical cut point of <54 mg/dl (<3.0 mmol/L) as a clinically relevant level with which to define meaningful hypoglycemia for trials of diabetes therapies; (2) utilization in clinical trials of mature glucose monitoring technologies for purposes of regulatory evaluation and clinical decision-making; and (3) development of primary efficacy endpoint composites that include hypoglycemia rates and glycemic control. Copyright © 2017 John Wiley & Sons, Ltd.

A new respirometric endpoint-based biosensor to assess the relative toxicity of chemicals on immobilized human cells.

PubMed

Dragone, Roberto; Frazzoli, Chiara; Grappelli, Claudio; Campanella, Luigi

2009-01-01

Several functional and biochemical parameters have been proposed as biomarkers of effect of environmental pollutants. A rapid biosensor working with immobilized human U-937 cells was developed and applied to environmentally relevant chemicals with different structures and toxicological pathways, i.e. benzalkonium chloride, clofibric acid, diclofenac, mercury nitrate, ofloxacin, and sodium dodecyl sulphate. Respiration of cells was relied upon as a comprehensive biochemical effect for screening purposes. Analytical parameter (DeltappmO(2)) and toxicological index (respiratory inhibition, delta%) measured after 1h of exposure were utilized for dose-response relationship study. Results (toxicity rating scales based on delta(50)% and steepness) were compared with those obtained by the same approach previously optimized on Saccharomyces cerevisiae. The toxicity rating scale obtained by the biomarker based on human mitochondrial and cell metabolic activities compared well with previous scale obtained on yeast cells and with available in-vivo acute toxicity indexes; respiration was confirmed as toxicological endpoint reliably measurable by the biosensor.

Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints, and data collection requirements for clinical studies.

PubMed

Tzikas, Apostolos; Holmes, David R; Gafoor, Sameer; Ruiz, Carlos E; Blomström-Lundqvist, Carina; Diener, Hans-Christoph; Cappato, Riccardo; Kar, Saibal; Lee, Randal J; Byrne, Robert A; Ibrahim, Reda; Lakkireddy, Dhanunjaya; Soliman, Osama I; Nabauer, Michael; Schneider, Steffen; Brachmann, Johannes; Saver, Jeffrey L; Tiemann, Klaus; Sievert, Horst; Camm, A John; Lewalter, Thorsten

2017-01-01

The increasing interest in left atrial appendage occlusion (LAAO) for ischaemic stroke prevention in atrial fibrillation (AF) fuels the need for more clinical data on the safety and effectiveness of this therapy. Besides an assessment of the effectiveness of the therapy in specific patients groups, comparisons with pharmacological stroke prophylaxis, surgical approaches, and other device-based therapies are warranted. This paper documents the consensus reached among clinical experts in relevant disciplines from Europe and North America, European cardiology professional societies, and representatives from the medical device industry regarding definitions for parameters and endpoints to be assessed in clinical studies. Adherence to these definitions is proposed in order to achieve a consistent approach across clinical studies on LAAO among the involved stakeholders and various clinical disciplines and thereby facilitate continued evaluation of therapeutic strategies available. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

A novel bioassay using the barnacle Amphibalanus amphitrite to evaluate chronic effects of aluminium, gallium and molybdenum in tropical marine receiving environments.

PubMed

van Dam, Joost W; Trenfield, Melanie A; Harries, Simon J; Streten, Claire; Harford, Andrew J; Parry, David; van Dam, Rick A

2016-11-15

A need exists for appropriate tools to evaluate risk and monitor potential effects of contaminants in tropical marine environments, as currently impact assessments are conducted by non-representative approaches. Here, a novel bioassay is presented that allows for the estimation of the chronic toxicity of contaminants in receiving tropical marine environments. The bioassay is conducted using planktonic larvae of the barnacle Amphibalanus amphitrite and is targeted at generating environmentally relevant, chronic toxicity data for water quality guideline derivation or compliance testing. The developmental endpoint demonstrated a consistently high control performance, validated through the use of copper as a reference toxicant. In addition, the biological effects of aluminium, gallium and molybdenum were assessed. The endpoint expressed high sensitivity to copper and moderate sensitivity to aluminium, whereas gallium and molybdenum exhibited no discernible effects, even at high concentrations, providing valuable information on the toxicity of these elements in tropical marine waters. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

[HTA-Perspective: Challenges in the early assessment of new oncological drugs].

PubMed

Wild, Claudia; Nachtnebel, Anna

2013-01-01

Oncologic drug therapies have gained wide attention in the context of health policy priority setting for serious and socially significant diseases with high human and monetary costs. Due to uncertainties and scepticism about the actual therapeutic importance of newly approved oncology products, an early assessment programme was already established in Austria in 2007. The assessment of new oncology products is thereby faced with special challenges, since study populations are frequently not representative or the study design is laid out in such a manner that a definitive assessment of patient-relevant endpoints is not possible (cross-overs after interim assessments, surrogate parameters as primary endpoints, uncontrolled studies or those with unrealistic comparators, invalidated post-hoc identified biomarkers). On account of these major uncertainties, even the European Medicines Agency (EMA) is already contemplating multi-stage, "adaptive" approvals, and national reimbursement institutions are increasingly working with outcome-oriented, conditional reimbursement. (As supplied by publisher). Copyright © 2013. Published by Elsevier GmbH.

Use of nutrigenomics endpoints in dietary interventions.

PubMed

Hendriks, Henk F J

2013-08-01

In this paper, the nutrigenomics approach is discussed as a research tool to study the physiological effects of nutrition and consequently how nutrition affects health and disease (endpoints). Nutrigenomics is the study of the effects of foods and food constituents on gene expression; the analyses include analysis of mRNA, proteins and metabolites. Nutrigenomics may be useful in dealing with the challenges that nutrition research is facing; by integrating the description of numerous active genes and metabolic pathways stronger evidence and new biomarkers for subtle nutritional effects may be obtained. Also, a new definition of disease and health may be needed. The use of tests challenging homoeostasis is being proposed to help define health. Challenge tests may be able to demonstrate in a better way subtle beneficial effects of nutrition on health. The paper describes some basic concepts relevant to nutrition research as well as some of the possibilities that are offered by nutrigenomics technology. Some of its applications are described.

Persistent high-risk human papillomavirus (HPV) infections as surrogate endpoints of progressive cervical disease. Potential new endpoint for efficacy studies with new-generation (non-HPV 16/18) prophylactic HPV vaccines.

PubMed

Syrjänen, K

2011-01-01

Recent data indicate that persistent HR-HPV infections represent a significantly increased risk of developing incident high-grade CIN and cervical cancer. Accordingly, 6-month (6M+) or 12-month (12M+) type-specific persistence of HR-HPV have been proposed as powerful surrogates of progressive disease. Because of substantial practical impact in future HPV vaccine trials using non-HPV 16/18 vaccines, studies on HR-HPV persistence as a surrogate endpoint of progressive CIN have been subject to a comprehensive meta-analyses recently. The present communication was solicited to bring this important and timely topic to the awareness of the readers, in a format consisting of a review of the recent literature, supplemented with the author's own experience from different studies. Based on a large number of relevant studies, there remains little doubt that persistence of HR-HPV for 6+ or 12+ months is associated with a significantly increased risk of developing incident high-grade CIN. However, some data also disclosed several important issues that need to be carefully considered and/or adequately resolved before adopting 6M+ or 12M+ HR-HPV persistence as a surrogate of progressive disease. These include i) definitions of HPV persistence, ii) HPV detection techniques and iii) testing intervals and iv) length of follow-up, as well as v) diagnosis of the surrogate endpoints, and vi) other study characteristics, including vii) the type of reference category used in calculating the risk estimates. All these issues are critically discussed in the present communication. Of major impact seems to be the reference category used to calculate these risk estimates, as evident from the NIS-LAMS cohort. Taken together, it is suggested that in all future studies using the 6M+ or 12M+ HR-HPV persistence as a surrogate endpoint of progressive disease, a "gold standard" should be used in calculating the risk estimates. In addition to deciding, 1) whether to use 6M+ or 12M+ persistence criteria, and 2) cytological, histological or combined surrogate endpoints (SIL, CIN1, CIN2, CIN/SIL), one should 3) use exclusively the HPV negative reference group in calculating the risk estimates for viral persistence endpoints. This is supported by the data from the recent meta-analysis as well as from the author's combined NIS-LAMS cohort, both implicating that the most consistent association to progressive disease is obtained when women with persistent HR-HPV are compared with HPV-negative women. It is the conviction of this author that the two other reference categories (HPV transient and HPV mixed outcome) are far too heterogeneous and subject to potential misclassifications to give consistent and reproducible risk estimates for HR-HPV persistence as a surrogate endpoint of progressive CIN.

Combining the assessment of apical endpoints and gene expression in the freshwater snail Physa acuta after exposure to reclaimed water.

PubMed

Aquilino, Mónica; Martínez-Guitarte, Jose Luis; García, Pilar; Beltrán, Eulalia Maria; Fernández, Carlos; Sánchez-Argüello, Paloma

2018-06-09

Post-treatment wastewater reuses are diverse. Recreational and environmental restoration uses of reclaimed water (RW) can be potentially harmful to aquatic organisms. In this work the freshwater snail Physa acuta was exposed to RW (100%) and its dilution (RW 50%). A simple laboratory mixture of three emerging pollutants was used to address the complex problem of mixture toxicity of RW. Hence fortified reclaimed water (FRW), obtained by adding fluoxetine (400 μg FLX/L), perfluorooctane sulphonic acid (90 μg PFOS/L) and methylparaben (9 μg MP/L), was tested at two dilution percentages: 100% and 50%. The effects of the laboratory mixture of FLX, PFOS and MP on the test medium were also studied. Long-lasting effects, together with early molecular responses, were assessed. Fecundity (cumulative egg production) over 21 days and the hatching of produced eggs (F1) after another 21-day embryonic exposure were monitored. The gene expression of three genes was analysed after 24 h of exposure: two endocrine-related nuclear receptors (ERR and RXR) and one stress protein gene (Hsp70). This reproduction test, with additional assessments of the F1 recovered eggs' hatching success, showed that both RW and FRW significantly reduced fecundity. F1 hatching was affected only by FRW. The gene expression results showed that the RXR response was strikingly similar to the fecundity response, which suggests that this nuclear receptor is involved in the reproductive pathways of gastropods. ERR remained virtually unaltered. Hsp70 was overexpressed by the laboratory mixture in the test medium, but no effect was observed in the fortification of RW. This opposite effect and lack of response for F1 hatching produced by the laboratory mixture in the test medium highlighted the difficulty of predicting mixture effects. The experimental approach allowed us to test the effects caused by RW on P. acuta at different biological organisation levels. Thus, the combination of molecular biomarkers and ecological relevant endpoints is a good strategy to test complex mixtures like RW as it provides a framework to link mechanisms of action and whole organism effects when it is almost impossible to detect the pollutant(s) that cause toxic effects. Published by Elsevier B.V.

Development and application of a density dependent matrix ...

EPA Pesticide Factsheets

Ranging along the Atlantic coast from US Florida to the Maritime Provinces of Canada, the Atlantic killifish (Fundulus heteroclitus) is an important and well-studied model organism for understanding the effects of pollutants and other stressors in estuarine and marine ecosystems. Matrix population models are useful tools for ecological risk assessment because they integrate effects across the life cycle, provide a linkage between endpoints observed in the individual and ecological risk to the population as a whole, and project outcomes for many generations in the future. We developed a density dependent matrix population model for Atlantic killifish by modifying a model developed for fathead minnow (Pimephales promelas) that has proved to be extremely useful, e.g. to incorporate data from laboratory studies and project effects of endocrine disrupting chemicals. We developed a size-structured model (as opposed to one that is based upon developmental stages or age class structure) so that we could readily incorporate output from a Dynamic Energy Budget (DEB) model, currently under development. Due to a lack of sufficient data to accurately define killifish responses to density dependence, we tested a number of scenarios realistic for other fish species in order to demonstrate the outcome of including this ecologically important factor. We applied the model using published data for killifish exposed to dioxin-like compounds, and compared our results to those using

A perspective on stream-catchment connections

USGS Publications Warehouse

Bencala, Kenneth E.

1993-01-01

Ecological study of the hyporheic zone is leading to recognition of a need for additional hydrologic understanding. Some of this understanding can be obtained by viewing the hyporheic zone as a succession of isolated boxes adjacent to the stream. Further understanding, particularly relevant to catchment-scale ecology, may come from studies focussed on the fluid mechanics of the flow-path connections between streams and their catchments.

Serrasalmidae — Piranhas and Pacus

USGS Publications Warehouse

Nico, Leo; Jegu, Michel; Andrade, Marcelo C

2017-01-01

The family Serrasalmidae is a morphologically and ecologically diverse group of South American freshwater fishes consisting of 16 genera and about 91 valid species. This chapter is a summary of the current state of knowledge on serrasalmid taxonomy, species richness, and ecology, and provides an identification key to the genera and references to relevant literature for species-level identifications. Included is information on native and non-native populations.

The National Ecosystem Services Classification System: A Framework for Identifying and Reducing Relevant Uncertainties

NASA Astrophysics Data System (ADS)

Rhodes, C. R.; Sinha, P.; Amanda, N.

2013-12-01

In recent years the gap between what scientists know and what policymakers should appreciate in environmental decision making has received more attention, as the costs of the disconnect have become more apparent to both groups. Particularly for water-related policies, the EPA's Office of Water has struggled with benefit estimates held low by the inability to quantify ecological and economic effects that theory, modeling, and anecdotal or isolated case evidence suggest may prove to be larger. Better coordination with ecologists and hydrologists is being explored as a solution. The ecosystem services (ES) concept now nearly two decades old links ecosystem functions and processes to the human value system. But there remains no clear mapping of which ecosystem goods and services affect which individual or economic values. The National Ecosystem Services Classification System (NESCS, 'nexus') project brings together ecologists, hydrologists, and social scientists to do this mapping for aquatic and other ecosystem service-generating systems. The objective is to greatly reduce the uncertainty in water-related policy making by mapping and ultimately quantifying the various functions and products of aquatic systems, as well as how changes to aquatic systems impact the human economy and individual levels of non-monetary appreciation for those functions and products. Primary challenges to fostering interaction between scientists, social scientists, and policymakers are lack of a common vocabulary, and the need for a cohesive comprehensive framework that organizes concepts across disciplines and accommodates scientific data from a range of sources. NESCS builds the vocabulary and the framework so both may inform a scalable transdisciplinary policy-making application. This talk presents for discussion the process and progress in developing both this vocabulary and a classifying framework capable of bridging the gap between a newer but existing ecosystem services classification system, and a standardized industrial classification system. Our goal is to model then predict the effects of a policy choice on the environment, from impacts on ecological components and processes all the way through to endpoints in the human value chain.

Effects of the fungicide metiram in outdoor freshwater microcosms: responses of invertebrates, primary producers and microbes.

PubMed

Lin, Ronghua; Buijse, Laura; Dimitrov, Mauricio R; Dohmen, Peter; Kosol, Sujitra; Maltby, Lorraine; Roessink, Ivo; Sinkeldam, Jos A; Smidt, Hauke; Van Wijngaarden, René P A; Brock, Theo C M

2012-07-01

The ecological impact of the dithiocarbamate fungicide metiram was studied in outdoor freshwater microcosms, consisting of 14 enclosures placed in an experimental ditch. The microcosms were treated three times (interval 7 days) with the formulated product BAS 222 28F (Polyram®). Intended metiram concentrations in the overlying water were 0, 4, 12, 36, 108 and 324 μg a.i./L. Responses of zooplankton, macroinvertebrates, phytoplankton, macrophytes, microbes and community metabolism endpoints were investigated. Dissipation half-life (DT₅₀) of metiram was approximately 1-6 h in the water column of the microcosm test system and the metabolites formed were not persistent. Multivariate analysis indicated treatment-related effects on the zooplankton (NOEC(community) = 36 μg a.i./L). Consistent treatment-related effects on the phytoplankton and macroinvertebrate communities and on the sediment microbial community could not be demonstrated or were minor. There was no evidence that metiram affected the biomass, abundance or functioning of aquatic hyphomycetes on decomposing alder leaves. The most sensitive populations in the microcosms comprised representatives of Rotifera with a NOEC of 12 μg a.i./L on isolated sampling days and a NOEC of 36 μg a.i./L on consecutive samplings. At the highest treatment-level populations of Copepoda (zooplankton) and the blue-green alga Anabaena (phytoplankton) also showed a short-term decline on consecutive sampling days (NOEC = 108 μg a.i./L). Indirect effects in the form of short-term increases in the abundance of a few macroinvertebrate and several phytoplankton taxa were also observed. The overall community and population level no-observed-effect concentration (NOEC(microcosm)) was 12-36 μg a.i./L. At higher treatment levels, including the test systems that received the highest dose, ecological recovery of affected measurement endpoints was fast (effect period < 8 weeks).

Recommendations for the development of rare disease drugs using the accelerated approval pathway and for qualifying biomarkers as primary endpoints.

PubMed

Kakkis, Emil D; O'Donovan, Mary; Cox, Gerald; Hayes, Mark; Goodsaid, Federico; Tandon, P K; Furlong, Pat; Boynton, Susan; Bozic, Mladen; Orfali, May; Thornton, Mark

2015-02-10

For rare serious and life-threatening disorders, there is a tremendous challenge of transforming scientific discoveries into new drug treatments. This challenge has been recognized by all stakeholders who endorse the need for flexibility in the regulatory review process for novel therapeutics to treat rare diseases. In the United States, the best expression of this flexibility was the creation of the Accelerated Approval (AA) pathway. The AA pathway is critically important for the development of treatments for diseases with high unmet medical need and has been used extensively for drugs used to treat cancer and infectious diseases like HIV.In 2012, the AA provisions were amended to enhance the application of the AA pathway to expedite the development of drugs for rare disorders under the Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA, among many provisions, requires the development of a more relevant FDA guidance on the types of evidence that may be acceptable in support of using a novel surrogate endpoint. The application of AA to rare diseases requires more predictability to drive greater access to appropriate use of AA for more rare disease treatments that might not be developed otherwise.This white paper proposes a scientific framework for assessing biomarker endpoints to enhance the development of novel therapeutics for rare and devastating diseases currently without adequate treatment and is based on the opinions of experts in drug development and rare disease patient groups. Specific recommendations include: 1) Establishing regulatory rationale for increased AA access in rare disease programs; 2) Implementing a Biomarker Qualification Request Process to provide the opportunity for an early determination of biomarker acceptance; and 3) A proposed scientific framework for qualifying biomarkers as primary endpoints. The paper's final section highlights case studies of successful examples that have incorporated biomarker endpoints into FDA approvals for rare disease therapies. The focus of this paper is on the situation in the Unites States, but the recommendations are reasonably applicable to any jurisdiction.

Identifying and designing chemicals with minimal acute aquatic toxicity

PubMed Central

Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T.; Zimmerman, Julie Beth

2015-01-01

Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure–activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical–chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard. PMID:24639521

Identifying and designing chemicals with minimal acute aquatic toxicity.

PubMed

Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T; Zimmerman, Julie Beth

2015-05-19

Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure-activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical-chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard.

A framework for predicting impacts on ecosystem services ...

EPA Pesticide Factsheets

Protection of ecosystem services is increasingly emphasized as a risk-assessment goal, but there are wide gaps between current ecological risk-assessment endpoints and potential effects on services provided by ecosystems. The authors present a framework that links common ecotoxicological endpoints to chemical impacts on populations and communities and the ecosystem services that they provide. This framework builds on considerable advances in mechanistic effects models designed to span multiple levels of biological organization and account for various types of biological interactions and feedbacks. For illustration, the authors introduce 2 case studies that employ well-developed and validated mechanistic effects models: the inSTREAM individual-based model for fish populations and the AQUATOX ecosystem model. They also show how dynamic energy budget theory can provide a common currency for interpreting organism-level toxicity. They suggest that a framework based on mechanistic models that predict impacts on ecosystem services resulting from chemical exposure, combined with economic valuation, can provide a useful approach for informing environmental management. The authors highlight the potential benefits of using this framework as well as the challenges that will need to be addressed in future work. The framework introduced here represents an ongoing initiative supported by the National Institute of Mathematical and Biological Synthesis (NIMBioS; http://www.nimbi

A Socio-Ecological Approach for Identifying and Contextualising Spatial Ecosystem-Based Adaptation Priorities at the Sub-National Level

PubMed Central

Bourne, Amanda; Holness, Stephen; Holden, Petra; Scorgie, Sarshen; Donatti, Camila I.; Midgley, Guy

2016-01-01

Climate change adds an additional layer of complexity to existing sustainable development and biodiversity conservation challenges. The impacts of global climate change are felt locally, and thus local governance structures will increasingly be responsible for preparedness and local responses. Ecosystem-based adaptation (EbA) options are gaining prominence as relevant climate change solutions. Local government officials seldom have an appropriate understanding of the role of ecosystem functioning in sustainable development goals, or access to relevant climate information. Thus the use of ecosystems in helping people adapt to climate change is limited partially by the lack of information on where ecosystems have the highest potential to do so. To begin overcoming this barrier, Conservation South Africa in partnership with local government developed a socio-ecological approach for identifying spatial EbA priorities at the sub-national level. Using GIS-based multi-criteria analysis and vegetation distribution models, the authors have spatially integrated relevant ecological and social information at a scale appropriate to inform local level political, administrative, and operational decision makers. This is the first systematic approach of which we are aware that highlights spatial priority areas for EbA implementation. Nodes of socio-ecological vulnerability are identified, and the inclusion of areas that provide ecosystem services and ecological resilience to future climate change is innovative. The purpose of this paper is to present and demonstrate a methodology for combining complex information into user-friendly spatial products for local level decision making on EbA. The authors focus on illustrating the kinds of products that can be generated from combining information in the suggested ways, and do not discuss the nuance of climate models nor present specific technical details of the model outputs here. Two representative case studies from rural South Africa demonstrate the replicability of this approach in rural and peri-urban areas of other developing and least developed countries around the world. PMID:27227671

A Socio-Ecological Approach for Identifying and Contextualising Spatial Ecosystem-Based Adaptation Priorities at the Sub-National Level.

PubMed

Bourne, Amanda; Holness, Stephen; Holden, Petra; Scorgie, Sarshen; Donatti, Camila I; Midgley, Guy

2016-01-01

Climate change adds an additional layer of complexity to existing sustainable development and biodiversity conservation challenges. The impacts of global climate change are felt locally, and thus local governance structures will increasingly be responsible for preparedness and local responses. Ecosystem-based adaptation (EbA) options are gaining prominence as relevant climate change solutions. Local government officials seldom have an appropriate understanding of the role of ecosystem functioning in sustainable development goals, or access to relevant climate information. Thus the use of ecosystems in helping people adapt to climate change is limited partially by the lack of information on where ecosystems have the highest potential to do so. To begin overcoming this barrier, Conservation South Africa in partnership with local government developed a socio-ecological approach for identifying spatial EbA priorities at the sub-national level. Using GIS-based multi-criteria analysis and vegetation distribution models, the authors have spatially integrated relevant ecological and social information at a scale appropriate to inform local level political, administrative, and operational decision makers. This is the first systematic approach of which we are aware that highlights spatial priority areas for EbA implementation. Nodes of socio-ecological vulnerability are identified, and the inclusion of areas that provide ecosystem services and ecological resilience to future climate change is innovative. The purpose of this paper is to present and demonstrate a methodology for combining complex information into user-friendly spatial products for local level decision making on EbA. The authors focus on illustrating the kinds of products that can be generated from combining information in the suggested ways, and do not discuss the nuance of climate models nor present specific technical details of the model outputs here. Two representative case studies from rural South Africa demonstrate the replicability of this approach in rural and peri-urban areas of other developing and least developed countries around the world.

Unrequited: neurochemical enhancement of love.

PubMed

Bamford, Rebecca

2015-07-01

I raise several concerns with Earp and colleagues' analysis of enhancement through neurochemical modulation of love as a key issue in contemporary neuroethics. These include: (i) strengthening their deflation of medicalization concerns by showing how the objection that love should be left outside of the scope of medicine would directly undermine the goal of medicine; (ii) developing stronger analysis of the social and political concerns relevant to neurochemical modulation of love, by exploring and suggesting possible counters to ways in which 'wellbeing' may be used as a tool of oppression; (iii) providing reasons to support a broad need for ecological investigation of, and indeed ecological education concerning, neurotechnology; (iv) suggesting ways in which philosophy, and the humanities more broadly, remain directly relevant to responding effectively to issues in contemporary neuroethics.

Environmentally relevant concentrations of microplastic particles influence larval fish ecology.

PubMed

Lönnstedt, Oona M; Eklöv, Peter

2016-06-03

The widespread occurrence and accumulation of plastic waste in the environment have become a growing global concern over the past decade. Although some marine organisms have been shown to ingest plastic, few studies have investigated the ecological effects of plastic waste on animals. Here we show that exposure to environmentally relevant concentrations of microplastic polystyrene particles (90 micrometers) inhibits hatching, decreases growth rates, and alters feeding preferences and innate behaviors of European perch (Perca fluviatilis) larvae. Furthermore, individuals exposed to microplastics do not respond to olfactory threat cues, which greatly increases predator-induced mortality rates. Our results demonstrate that microplastic particles operate both chemically and physically on larval fish performance and development. Copyright © 2016, American Association for the Advancement of Science.

Big biology meets microclimatology: Defining thermal niches of ectotherms at landscape scales for conservation planning

Treesearch

Daniel J. Isaak; Seth J. Wenger; Michael K. Young

2017-01-01

Temperature profoundly affects ecology, a fact ever more evident as the ability to measure thermal environments increases and global changes alter these environments. The spatial structure of thermalscapes is especially relevant to the distribution and abundance of ectothermic organisms but the ability to describe biothermal relationships at extents and grains relevant...

Data communications in a parallel active messaging interface of a parallel computer

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2015-02-03

Data communications in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, endpoints coupled for data communications through the PAMI and through data communications resources, including receiving in an origin endpoint of the PAMI a SEND instruction, the SEND instruction specifying a transmission of transfer data from the origin endpoint to a first target endpoint; transmitting from the origin endpoint to the first target endpoint a Request-To-Send (`RTS`) message advising the first target endpoint of the location and size of the transfer data; assigning by the first target endpoint to each of a plurality of target endpoints separate portions of the transfer data; and receiving by the plurality of target endpoints the transfer data.

Data communications in a parallel active messaging interface of a parallel computer

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2014-11-18

Data communications in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, endpoints coupled for data communications through the PAMI and through data communications resources, including receiving in an origin endpoint of the PAMI a SEND instruction, the SEND instruction specifying a transmission of transfer data from the origin endpoint to a first target endpoint; transmitting from the origin endpoint to the first target endpoint a Request-To-Send (`RTS`) message advising the first target endpoint of the location and size of the transfer data; assigning by the first target endpoint to each of a plurality of target endpoints separate portions of the transfer data; and receiving by the plurality of target endpoints the transfer data.

How Neighborhoods Influence Health: Lessons to be learned from the application of political ecology

PubMed Central

Chitewere, Tendai; Shim, Janet K.; Barker, Judith C.; Yen, Irene H.

2017-01-01

AIM This paper articulates how political ecology can be a useful tool for asking fundamental questions and applying relevant methods to investigate structures that impact relationship between neighborhood and health. Through a narrative analysis, we identify how political ecology can develop our future agendas for neighborhood-health research as it relates to social, political, environmental, and economic structures. Political ecology makes clear the connection between political economy and neighborhood by highlighting the historical and structural processes that produce and maintain social inequality, which affect health and well-being. These concepts encourage researchers to examine how people construct neighborhood and health in different ways that, in turn, can influence different health outcomes and, thus, efforts to address solutions. PMID:28342425

Integrated structural biology and molecular ecology of N-cycling enzymes from ammonia-oxidizing archaea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tolar, Bradley B.; Herrmann, Jonathan; Bargar, John R.

In this paper, knowledge of the molecular ecology and environmental determinants of ammonia-oxidizing organisms is critical to understanding and predicting the global nitrogen (N) and carbon cycles, but an incomplete biochemical picture hinders in vitro studies of N-cycling enzymes. Although an integrative structural and dynamic characterization at the atomic scale would advance our understanding of function tremendously, structural knowlede of key N-cycling enzymes from ecologically-relevant ammonia oxidizers is unfortunately extremely limited. Here, we discuss the challenges and opportunities for examining the ecology of ammonia-oxidizing organisms, particularly uncultivated Thaumarchaeota, though (meta)genome-driven structural biology of the enzymes ammonia monooxygenase (AMO) andmore » nitrite reductase (NirK).« less

Integrated structural biology and molecular ecology of N-cycling enzymes from ammonia-oxidizing archaea

DOE PAGES

Tolar, Bradley B.; Herrmann, Jonathan; Bargar, John R.; ...

2017-07-05

In this paper, knowledge of the molecular ecology and environmental determinants of ammonia-oxidizing organisms is critical to understanding and predicting the global nitrogen (N) and carbon cycles, but an incomplete biochemical picture hinders in vitro studies of N-cycling enzymes. Although an integrative structural and dynamic characterization at the atomic scale would advance our understanding of function tremendously, structural knowlede of key N-cycling enzymes from ecologically-relevant ammonia oxidizers is unfortunately extremely limited. Here, we discuss the challenges and opportunities for examining the ecology of ammonia-oxidizing organisms, particularly uncultivated Thaumarchaeota, though (meta)genome-driven structural biology of the enzymes ammonia monooxygenase (AMO) andmore » nitrite reductase (NirK).« less

Integrated structural biology and molecular ecology of N-cycling enzymes from ammonia-oxidizing archaea.

PubMed

Tolar, Bradley B; Herrmann, Jonathan; Bargar, John R; van den Bedem, Henry; Wakatsuki, Soichi; Francis, Christopher A

2017-10-01

Knowledge of the molecular ecology and environmental determinants of ammonia-oxidizing organisms is critical to understanding and predicting the global nitrogen (N) and carbon cycles, but an incomplete biochemical picture hinders in vitro studies of N-cycling enzymes. Although an integrative structural and dynamic characterization at the atomic scale would advance our understanding of function tremendously, structural knowledge of key N-cycling enzymes from ecologically relevant ammonia oxidizers is unfortunately extremely limited. Here, we discuss the challenges and opportunities for examining the ecology of ammonia-oxidizing organisms, particularly uncultivated Thaumarchaeota, through (meta)genome-driven structural biology of the enzymes ammonia monooxygenase (AMO) and nitrite reductase (NirK). © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

How Neighborhoods Influence Health: Lessons to be learned from the application of political ecology.

PubMed

Chitewere, Tendai; Shim, Janet K; Barker, Judith C; Yen, Irene H

2017-05-01

This paper articulates how political ecology can be a useful tool for asking fundamental questions and applying relevant methods to investigate structures that impact relationship between neighborhood and health. Through a narrative analysis, we identify how political ecology can develop our future agendas for neighborhood-health research as it relates to social, political, environmental, and economic structures. Political ecology makes clear the connection between political economy and neighborhood by highlighting the historical and structural processes that produce and maintain social inequality, which affect health and well-being. These concepts encourage researchers to examine how people construct neighborhood and health in different ways that, in turn, can influence different health outcomes and, thus, efforts to address solutions. Published by Elsevier Ltd.

Effects of metal and predator stressors in larval southern toads (Anaxyrus terrestris).

PubMed

Rumrill, Caitlin T; Scott, David E; Lance, Stacey L

2016-08-01

Natural and anthropogenic stressors typically do not occur in isolation; therefore, understanding ecological risk of contaminant exposure should account for potential interactions of multiple stressors. Realistically, common contaminants can also occur chronically in the environment. Because parental exposure to stressors may cause transgenerational effects on offspring, affecting their ability to cope with the same or novel environmental stressors, the exposure histories of generations preceding that being tested should be considered. To examine multiple stressor and parental exposure effects we employed a 2 × 2 × 2 factorial design in outdoor 1000-L mesocosms (n = 24). Larval southern toads (Anaxyrus terrestris), bred from parents collected from reference and metal-contaminated sites, were exposed to two levels of both an anthropogenic (copper-0, 30 µg/L Cu) and natural (predator cue - present/absent) stressor and reared to metamorphosis. Toads from the metal-contaminated parental source population were smaller at metamorphosis and had delayed development; i.e., a prolonged larval period. Similarly, larval Cu exposure also reduced size at metamorphosis and prolonged the larval period. We, additionally, observed a significant interaction between larval Cu and predator-cue exposure on larval period, wherein delayed emergence was only present in the 30-µg/L Cu treatments in the absence of predator cues. The presence of parental effects as well as an interaction between aquatic stressors on commonly measured endpoints highlight the importance of conducting multistressor studies across generations to obtain data that are more relevant to field conditions in order to determine population-level effects of contaminant exposure.

The usefulness of a sediment bioassay with the gastropod Nassarius reticulatus in tributyltin monitoring programs.

PubMed

Laranjeiro, Filipe; Pérez, Sara; Navarro, Patricia; Carrero, José Antonio; Beiras, Ricardo

2015-11-01

Despite the use of tributyltin (TBT) had been banned worldwide in 2008 there is still evidence of its deleterious presence in environment. We evaluate the usefulness of a 28days sediment bioassay with Nassarius reticulatus females to monitor TBT pollution, using imposex as endpoint. In addition, butyltins were determined in sediments and tissues, and, whenever posible, imposex was assessed in native N. reticulatus at the same sites where sediments were sampled. In the bioassay, a significant increase in imposex parameters was obtained with three sediments (Vi2, Vi3, and Vi4). No correlation was found between this and TBT concentrations in sediment although good correlations were obtained for TBT in tissues, putting in evidence TBT bioavailability in sediment. A significant decrease in imposex from 2008 to 2013 in native snails was only observed at sites that did not cause any effect in the bioassay. In contrast, imposex levels in 2013 were kept as high as 2008 in one of the sites where a significant imposex increase in the bioassay was observed. The bioassay proves thus to be a practical and ecological relevant tool, as: (i) it can be conducted in sites with no native populations of snails, (ii) it provides early identification of polluted sites, anticipating future imposex levels or early identification of recovering, and (iii) it yields information on the bioavailable fraction of the TBT in the sediment. Therefore, this tool can be of extreme usefulness under the scope of recent European legislative frameworks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multi-laboratory evaluations of the performance of Catellicoccus marimammalium PCR assays developed to target gull fecal sources

USGS Publications Warehouse

Sinigalliano, Christopher D.; Ervin, Jared S.; Van De Werfhorst, Laurie C.; Badgley, Brian D.; Ballestée, Elisenda; Bartkowiaka, Jakob; Boehm, Alexandria B.; Byappanahalli, Muruleedhara N.; Goodwin, Kelly D.; Gourmelon, Michèle; Griffith, John; Holden, Patricia A.; Jay, Jenny; Layton, Blythe; Lee, Cheonghoon; Lee, Jiyoung; Meijer, Wim G.; Noble, Rachel; Raith, Meredith; Ryu, Hodon; Sadowsky, Michael J.; Schriewer, Alexander; Wang, Dan; Wanless, David; Whitman, Richard; Wuertz, Stefan; Santo Domingo, Jorge W.

2013-01-01

Here we report results from a multi-laboratory (n = 11) evaluation of four different PCR methods targeting the 16S rRNA gene of Catellicoccus marimammalium originally developed to detect gull fecal contamination in coastal environments. The methods included a conventional end-point PCR method, a SYBR® Green qPCR method, and two TaqMan® qPCR methods. Different techniques for data normalization and analysis were tested. Data analysis methods had a pronounced impact on assay sensitivity and specificity calculations. Across-laboratory standardization of metrics including the lower limit of quantification (LLOQ), target detected but not quantifiable (DNQ), and target not detected (ND) significantly improved results compared to results submitted by individual laboratories prior to definition standardization. The unit of measure used for data normalization also had a pronounced effect on measured assay performance. Data normalization to DNA mass improved quantitative method performance as compared to enterococcus normalization. The MST methods tested here were originally designed for gulls but were found in this study to also detect feces from other birds, particularly feces composited from pigeons. Sequencing efforts showed that some pigeon feces from California contained sequences similar to C. marimammalium found in gull feces. These data suggest that the prevalence, geographic scope, and ecology of C. marimammalium in host birds other than gulls require further investigation. This study represents an important first step in the multi-laboratory assessment of these methods and highlights the need to broaden and standardize additional evaluations, including environmentally relevant target concentrations in ambient waters from diverse geographic regions.

Movement trajectory smoothness is not associated with the endpoint accuracy of rapid multi-joint arm movements in young and older adults

PubMed Central

Poston, Brach; Van Gemmert, Arend W.A.; Sharma, Siddharth; Chakrabarti, Somesh; Zavaremi, Shahrzad H.; Stelmach, George

2013-01-01

The minimum variance theory proposes that motor commands are corrupted by signal-dependent noise and smooth trajectories with low noise levels are selected to minimize endpoint error and endpoint variability. The purpose of the study was to determine the contribution of trajectory smoothness to the endpoint accuracy and endpoint variability of rapid multi-joint arm movements. Young and older adults performed arm movements (4 blocks of 25 trials) as fast and as accurately as possible to a target with the right (dominant) arm. Endpoint accuracy and endpoint variability along with trajectory smoothness and error were quantified for each block of trials. Endpoint error and endpoint variance were greater in older adults compared with young adults, but decreased at a similar rate with practice for the two age groups. The greater endpoint error and endpoint variance exhibited by older adults were primarily due to impairments in movement extent control and not movement direction control. The normalized jerk was similar for the two age groups, but was not strongly associated with endpoint error or endpoint variance for either group. However, endpoint variance was strongly associated with endpoint error for both the young and older adults. Finally, trajectory error was similar for both groups and was weakly associated with endpoint error for the older adults. The findings are not consistent with the predictions of the minimum variance theory, but support and extend previous observations that movement trajectories and endpoints are planned independently. PMID:23584101

Shades of green: Measuring the ecology of urban green space in the context of human health and well-being

Treesearch

Anna Jorgensen; Paul H. Gobster

2010-01-01

In this paper we review and analyze the recent research literature on urban green space and human health and well-being, with an emphasis on studies that attempt to measure biodiversity and other green space concepts relevant to urban ecological restoration. We first conduct a broad scale assessment of the literature to identify typologies of urban green space and...

The ecology of anaerobic degraders of BTEX hydrocarbons in aquifers

PubMed Central

Lueders, Tillmann

2017-01-01

Abstract The degradation of benzene, toluene, ethylbenzene and xylene (BTEX) contaminants in groundwater relies largely on anaerobic processes. While the physiology and biochemistry of selected relevant microbes have been intensively studied, research has now started to take the generated knowledge back to the field, in order to trace the populations truly responsible for the anaerobic degradation of BTEX hydrocarbons in situ and to unravel their ecology in contaminated aquifers. Here, recent advances in our knowledge of the identity, diversity and ecology of microbes involved in these important ecosystem services are discussed. At several sites, distinct lineages within the Desulfobulbaceae, the Rhodocyclaceae and the Gram-positive Peptococcaceae have been shown to dominate the degradation of different BTEX hydrocarbons. Especially for the functional guild of anaerobic toluene degraders, specific molecular detection systems have been developed, allowing researchers to trace their diversity and distribution in contaminated aquifers. Their populations appear enriched in hot spots of biodegradation in situ. 13C-labelling experiments have revealed unexpected pathways of carbon sharing and obligate syntrophic interactions to be relevant in degradation. Together with feedback mechanisms between abiotic and biotic habitat components, this promotes an enhanced ecological perspective of the anaerobic degradation of BTEX hydrocarbons, as well as its incorporation into updated concepts for site monitoring and bioremediation. PMID:27810873

Recent advances in vertebrate and invertebrate transgenerational immunity in the light of ecology and evolution.

PubMed

Roth, Olivia; Beemelmanns, Anne; Barribeau, Seth M; Sadd, Ben M

2018-06-18

Parental experience with parasites and pathogens can lead to increased offspring resistance to infection, through a process known as transgenerational immune priming (TGIP). Broadly defined, TGIP occurs across a wide range of taxa, and can be viewed as a type of phenotypic plasticity, with hosts responding to the pressures of relevant local infection risk by altering their offspring's immune defenses. There are ever increasing examples of both invertebrate and vertebrate TGIP, which go beyond classical examples of maternal antibody transfer. Here we critically summarize the current evidence for TGIP in both invertebrates and vertebrates. Mechanisms underlying TGIP remain elusive in many systems, but while it is unlikely that they are conserved across the range of organisms with TGIP, recent insight into epigenetic modulation may challenge this view. We place TGIP into a framework of evolutionary ecology, discussing costs and relevant environmental variation. We highlight how the ecology of species or populations should affect if, where, when, and how TGIP is realized. We propose that the field can progress by incorporating evolutionary ecology focused designs to the study of the so far well chronicled, but mostly descriptive TGIP, and how rapidly developing -omic methods can be employed to further understand TGIP across taxa.

Mayan Children's Creation of Learning Ecologies by Initiative and Cooperative Action.

PubMed

de León, Lourdes

2015-01-01

This chapter examines Mayan children's initiatives in creating their own learning environments in collaboration with others as they engage in culturally relevant endeavors of family and community life. To this end, I carry out a fine-grained ethnographic and linguistic analysis of the interactional emergence of learning ecologies. Erickson defines learning ecology as a socioecological system where participants mutually influence one another through verbal and nonverbal actions, as well as through other forms of semiotic communication (2010, 254). In analyzing learning ecologies, I adopt a "theory of action" approach, taking into account multimodal communication (e.g., talk, gesture, gaze, body positioning), participants' sociospatial organization, embodied action, objects, tools, and other culturally relevant materials brought together to build action (Goodwin, 2000, 2013; Hutchins, 1995). I use microethnographic analysis (Erickson, 1992) to bring to the surface central aspects of children's agentive roles in learning through "cooperative actions" (Goodwin, 2013) and "hands-on" experience (Ingold, 2007) the skills of competent members of their community. I examine three distinct Learning Ecologies created by children's initiatives among the Mayan children that I observed: (i) children requesting guidance to collaborate in a task, (ii) older children working on their own initiative with subsequent monitoring and correction from competent members, and (iii) children with near competence in a task with occasional monitoring and no guidance. I argue that these findings enrich and add power to models of family- and community-based learning such as Learning by Observing and Pitching In (Rogoff, 2014). © 2015 Elsevier Inc. All rights reserved.

A Risk-Based Ecohydrological Approach to Assessing Environmental Flow Regimes

NASA Astrophysics Data System (ADS)

Mcgregor, Glenn B.; Marshall, Jonathan C.; Lobegeiger, Jaye S.; Holloway, Dean; Menke, Norbert; Coysh, Julie

2018-03-01

For several decades there has been recognition that water resource development alters river flow regimes and impacts ecosystem values. Determining strategies to protect or restore flow regimes to achieve ecological outcomes is a focus of water policy and legislation in many parts of the world. However, consideration of existing environmental flow assessment approaches for application in Queensland identified deficiencies precluding their adoption. Firstly, in managing flows and using ecosystem condition as an indicator of effectiveness, many approaches ignore the fact that river ecosystems are subjected to threatening processes other than flow regime alteration. Secondly, many focus on providing flows for responses without considering how often they are necessary to sustain ecological values in the long-term. Finally, few consider requirements at spatial-scales relevant to the desired outcomes, with frequent focus on individual places rather than the regions supporting sustainability. Consequently, we developed a risk-based ecohydrological approach that identifies ecosystem values linked to desired ecological outcomes, is sensitive to flow alteration and uses indicators of broader ecosystem requirements. Monitoring and research is undertaken to quantify flow-dependencies and ecological modelling is used to quantify flow-related ecological responses over an historical flow period. The relative risk from different flow management scenarios can be evaluated at relevant spatial-scales. This overcomes the deficiencies identified above and provides a robust and useful foundation upon which to build the information needed to support water planning decisions. Application of the risk assessment approach is illustrated here by two case studies.

Chest physiotherapy can affect the lung clearance index in cystic fibrosis patients.

PubMed

Grosse-Onnebrink, Joerg; Mellies, Uwe; Olivier, Margarete; Werner, Claudius; Stehling, Florian

2017-05-01

The lung clearance index (LCI) is determined by multiple-breath washout lung function (MBW). It is increasingly used as an endpoint in clinical trials. Chest physiotherapy (CP) is part of routine cystic fibrosis (CF) care. Whether the LCI is useful in detecting short-term treatment effects of CP has not been sufficiently investigated. We assessed the short-term influence of CP with highly standardized high-frequency chest wall oscillation (HFCWO) on the LCI in CF patients. In this randomized controlled study, the LCI was obtained in 20 CF patients (7-34 years) hospitalized for infective pulmonary exacerbation prior to and immediately after a single treatment of HFCWO. Twenty-one control group CF patients (7-51 years) received no treatment. We calculated the coefficient of repeatability (CR) to estimate the clinical relevance of possible treatment effects. HFCWO improved (ie, decreased) the LCI by a median of 0.9 (range -0.45; 3.47; P = 0.002); the LCI decreased in 15 of 20 intervention group patients. In five patients the decrease in LCI exceeded the CR (2.15), indicating a clinically relevant treatment effect; in five patients the LCI increased but did not exceed the CR. The LCI did not change significantly in the control group patients. HFCWO can have a short-term decreasing effect on the LCI, but the treatment response is heterogeneous. In future trials using LCI as an endpoint, the timing of CP in relation to MBW should be considered a possible bias. © 2017 Wiley Periodicals, Inc.

A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lips, Irene M., E-mail: i.m.lips@umcutrecht.nl; Gils, Carla H. van; Kotte, Alexis N.T.J.

2012-06-01

Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondarymore » outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.« less

Evaluation of food-relevant chemicals in the ToxCast high ...

EPA Pesticide Factsheets

There are thousands of chemicals that are directly added to or come in contact with food, many of which have undergone little to no toxicological evaluation. The ToxCast high-throughput screening (HTS) program has evaluated over 1,800 chemicals in concentration-response across ~820 assay endpoints and continues to grow; with all data completely available to the public, this resource serves as a unique opportunity to evaluate the bioactivity of chemicals in vitro. This study investigated the chemical landscape of the food-relevant chemical universe using cheminformatics analyses, and subsequently evaluated the bioactivity of food-relevant chemicals included in the ToxCast HTS program. Initially, a list of 9,437 food-relevant chemicals was compiled by comprehensively mining publicly available sources for direct food additives, food contact substances, indirect food additives, and pesticides. Of these food-relevant chemicals, 4,638 were associated with curated structure definition files amenable to defining physical/chemical features used to generate chemical fingerprints. Clustering was conducted based on the chemical fingerprints using a self-organizing map approach. This revealed that pesticides, food contact substances, and direct food additives generally clustered apart from one another, supporting that these categories reflect not only different uses but also distinct chemistries. Subsequently, 967 of the 9,437 food-relevant chemicals were identified in the T

Eco-HAB as a fully automated and ecologically relevant assessment of social impairments in mouse models of autism.

PubMed

Puścian, Alicja; Łęski, Szymon; Kasprowicz, Grzegorz; Winiarski, Maciej; Borowska, Joanna; Nikolaev, Tomasz; Boguszewski, Paweł M; Lipp, Hans-Peter; Knapska, Ewelina

2016-10-12

Eco-HAB is an open source, RFID-based system for automated measurement and analysis of social preference and in-cohort sociability in mice. The system closely follows murine ethology. It requires no contact between a human experimenter and tested animals, overcoming the confounding factors that lead to irreproducible assessment of murine social behavior between laboratories. In Eco-HAB, group-housed animals live in a spacious, four-compartment apparatus with shadowed areas and narrow tunnels, resembling natural burrows. Eco-HAB allows for assessment of the tendency of mice to voluntarily spend time together in ethologically relevant mouse group sizes. Custom-made software for automated tracking, data extraction, and analysis enables quick evaluation of social impairments. The developed protocols and standardized behavioral measures demonstrate high replicability. Unlike classic three-chambered sociability tests, Eco-HAB provides measurements of spontaneous, ecologically relevant social behaviors in group-housed animals. Results are obtained faster, with less manpower, and without confounding factors.

Understanding psychiatric disorder by capturing ecologically relevant features of learning and decision-making.

PubMed

Scholl, Jacqueline; Klein-Flügge, Miriam

2017-09-28

Recent research in cognitive neuroscience has begun to uncover the processes underlying increasingly complex voluntary behaviours, including learning and decision-making. Partly this success has been possible by progressing from simple experimental tasks to paradigms that incorporate more ecological features. More specifically, the premise is that to understand cognitions and brain functions relevant for real life, we need to introduce some of the ecological challenges that we have evolved to solve. This often entails an increase in task complexity, which can be managed by using computational models to help parse complex behaviours into specific component mechanisms. Here we propose that using computational models with tasks that capture ecologically relevant learning and decision-making processes may provide a critical advantage for capturing the mechanisms underlying symptoms of disorders in psychiatry. As a result, it may help develop mechanistic approaches towards diagnosis and treatment. We begin this review by mapping out the basic concepts and models of learning and decision-making. We then move on to consider specific challenges that emerge in realistic environments and describe how they can be captured by tasks. These include changes of context, uncertainty, reflexive/emotional biases, cost-benefit decision-making, and balancing exploration and exploitation. Where appropriate we highlight future or current links to psychiatry. We particularly draw examples from research on clinical depression, a disorder that greatly compromises motivated behaviours in real-life, but where simpler paradigms have yielded mixed results. Finally, we highlight several paradigms that could be used to help provide new insights into the mechanisms of psychiatric disorders. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Promise and progress in environmental genomics: a status report on the applications of gene expression-based microarray studies in ecologically relevant fish species.

PubMed

Hook, S E

2010-12-01

The advent of any new technology is typically met with great excitement. So it was a few years ago, when the combination of advances in sequencing technology and the development of microarray technology made measurements of global gene expression in ecologically relevant species possible. Many of the review papers published around that time promised that these new technologies would revolutionize environmental biology as they had revolutionized medicine and related fields. A few years have passed since these technological advancements have been made, and the use of microarray studies in non-model fish species has been adopted in many laboratories internationally. Has the relatively widespread adoption of this technology really revolutionized the fields of environmental biology, including ecotoxicology, aquaculture and ecology, as promised? Or have these studies merely become a novelty and a potential distraction for scientists addressing environmentally relevant questions? In this review, the promises made in early review papers, in particular about the advances that the use of microarrays would enable, are summarized; these claims are compared to the results of recent studies to determine whether the forecasted changes have materialized. Some applications, as discussed in the paper, have been realized and have led to advances in their field, others are still under development. © 2010 CSIRO. Journal of Fish Biology © 2010 The Fisheries Society of the British Isles.

Identification of hydrologic indicators related to fish diversity and abundance: A data mining approach for fish community analysis

NASA Astrophysics Data System (ADS)

Yang, Yi-Chen E.; Cai, Ximing; Herricks, Edwin E.

2008-04-01

This paper develops a new approach to identify hydrologic indicators related to fish community and generate a quantitative function between an ecological target index and the identified hydrologic indicators. The approach is based on genetic programming (GP), a data mining method. Using the Shannon Index (a fish community diversity index) or the number of individuals (total abundance) of a fish community, as an ecological target, the GP identified the most ecologically relevant hydrologic indicators (ERHIs) from 32 indicators of hydrologic alteration, for the case study site, the upper Illinois River. Robustness analysis showed that different GP runs found a similar set of ERHIs; each of the identified ERHI from different GP runs had a consistent relationship with the target index. By comparing the GP results with those from principal component analysis and autecology matrix, the three approaches identified a small number (six) of common ERHIs. Particularly, the timing of low flow (Dmin) seems to be more relevant to the diversity of the fish community, while the magnitude of the low flow (Qb) is more relevant to the total fish abundance; large rising rates result in a significant improvement of fish diversity, which is counterintuitive and against previous findings. The quantitative function developed by GP was further used to construct an indicator impact matrix (IIM), which was demonstrated as a potentially useful tool for streamflow restoration design.

Functions and ecological status of eight Italian lagoons examined using biological traits analysis (BTA).

PubMed

Marchini, Agnese; Munari, Cristina; Mistri, Michele

2008-06-01

The soft-bottom communities of eight Italian lagoons were analyzed for eight biological traits (feeding, mobility, adult life habitat, body size, life span, reproductive technique, type of larva and reproductive frequency) in order to identify the dominant traits in different transitional environments. We considered the ecological quality status (EcoQS) of the stations, assessed by two biotic indices, AMBI and Bentix. Stations were categorized into EcoQS classes to investigate the relationship between biological functions and ecological quality. The results indicate that the variability of the data was governed by traits linked to resource utilization rather than to life cycle. Lagoons affected by chronic disturbance displayed a poor functional composition, which usually corresponded to poor EcoQS in some cases, correlations between ecological groups and traits modalities were ecologically relevant; however, classes of EcoQS were found to be relatively independent from the functional structure of the considered stations.

Mastering Foreign Language Competence of Ecology and Environment Managers for Mining Industry of Kuzbass

NASA Astrophysics Data System (ADS)

Greenwald, Oksana; Islamov, Roman; Sergeychick, Tatyana

2017-11-01

The necessity to solve nature conservation problems of Kuzbass mining industry demands from postgraduate education institutions to train highly qualified specialists in ecology and environment management. As 21st century education is competence-based one, the article clarifies the concept of competence in education, focuses on key competences, namely foreign language competence and its relevance for specialists in ecology and environment management. Foreign language competence is acquired through the course of "Foreign Language" discipline which covers the following aspects: academic reading, academic writing and public speaking. The article also describes the experience of organizing students' individual work taking into account their motivation and specific conditions of the discipline as well. Thus, both the content of the discipline and the approach to organize students' learning contribute to mastering foreign language competence of ecology and environment managers as inherent condition of their professional efficiency for solving ecological problems of mining industry in Kuzbass region.

Where the wild things are: informal experience and ecological reasoning.

PubMed

Coley, John D

2012-01-01

Category-based induction requires selective use of different relations to guide inferences; this article examines the development of inferences based on ecological relations among living things. Three hundred and forty-six 6-, 8-, and 10-year-old children from rural, suburban, and urban communities projected novel diseases or insides from one species to an ecologically or taxonomically related species; they were also surveyed about hobbies and activities. Frequency of ecological inferences increased with age and with reports of informal exploration of nature, and decreased with population density. By age 10, children preferred taxonomic inferences for insides and ecological inferences for disease, but this pattern emerged earlier among rural children. These results underscore the importance of context by demonstrating effects of both domain-relevant experience and environment on biological reasoning. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Bringing an ecological view of change to Landsat-based remote sensing

USGS Publications Warehouse

Kennedy, Robert E.; Andrefouet, Serge; Cohen, Warren; Gomez, Cristina; Griffiths, Patrick; Hais, Martin; Healey, Sean; Helmer, Eileen H.; Hostert, Patrick; Lyons, Mitchell; Meigs, Garrett; Pflugmacher, Dirk; Phinn, Stuart; Powell, Scott; Scarth, Peter; Susmita, Sen; Schroeder, Todd A.; Schneider, Annemarie; Sonnenschein, Ruth; Vogelmann, James; Wulder, Michael A.; Zhu, Zhe

2014-01-01

When characterizing the processes that shape ecosystems, ecologists increasingly use the unique perspective offered by repeat observations of remotely sensed imagery. However, the concept of change embodied in much of the traditional remote-sensing literature was primarily limited to capturing large or extreme changes occurring in natural systems, omitting many more subtle processes of interest to ecologists. Recent technical advances have led to a fundamental shift toward an ecological view of change. Although this conceptual shift began with coarser-scale global imagery, it has now reached users of Landsat imagery, since these datasets have temporal and spatial characteristics appropriate to many ecological questions. We argue that this ecologically relevant perspective of change allows the novel characterization of important dynamic processes, including disturbances, long-term trends, cyclical functions, and feedbacks, and that these improvements are already facilitating our understanding of critical driving forces, such as climate change, ecological interactions, and economic pressures.

Relevance of randomised controlled trials in oncology.

PubMed

Tannock, Ian F; Amir, Eitan; Booth, Christopher M; Niraula, Saroj; Ocana, Alberto; Seruga, Bostjan; Templeton, Arnoud J; Vera-Badillo, Francisco

2016-12-01

Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather than commercial interest, avoid non-validated surrogate endpoints in registration trials, and have entry criteria that allow inclusion of all patients who are fit to receive treatment. Furthermore, RCTs should be reported with complete accounting of frequency and management of toxicities, and with strict guidelines to ensure freedom from bias. Premature reporting of results should be avoided. The bar for clinical benefit should be raised for drug registration, which should require publication and review of mature data from RCTs, post-marketing health outcome studies, and value-based pricing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation).

PubMed

Goodman, Shaun G; Wojdyla, Daniel M; Piccini, Jonathan P; White, Harvey D; Paolini, John F; Nessel, Christopher C; Berkowitz, Scott D; Mahaffey, Kenneth W; Patel, Manesh R; Sherwood, Matthew W; Becker, Richard C; Halperin, Jonathan L; Hacke, Werner; Singer, Daniel E; Hankey, Graeme J; Breithardt, Gunter; Fox, Keith A A; Califf, Robert M

2014-03-11

This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Contributions of cultural services to the ecosystem services agenda

PubMed Central

Daniel, Terry C.; Muhar, Andreas; Arnberger, Arne; Aznar, Olivier; Boyd, James W.; Chan, Kai M. A.; Costanza, Robert; Elmqvist, Thomas; Flint, Courtney G.; Gobster, Paul H.; Grêt-Regamey, Adrienne; Lave, Rebecca; Muhar, Susanne; Penker, Marianne; Ribe, Robert G.; Schauppenlehner, Thomas; Sikor, Thomas; Soloviy, Ihor; Spierenburg, Marja; Taczanowska, Karolina; Tam, Jordan; von der Dunk, Andreas

2012-01-01

Cultural ecosystem services (ES) are consistently recognized but not yet adequately defined or integrated within the ES framework. A substantial body of models, methods, and data relevant to cultural services has been developed within the social and behavioral sciences before and outside of the ES approach. A selective review of work in landscape aesthetics, cultural heritage, outdoor recreation, and spiritual significance demonstrates opportunities for operationally defining cultural services in terms of socioecological models, consistent with the larger set of ES. Such models explicitly link ecological structures and functions with cultural values and benefits, facilitating communication between scientists and stakeholders and enabling economic, multicriterion, deliberative evaluation and other methods that can clarify tradeoffs and synergies involving cultural ES. Based on this approach, a common representation is offered that frames cultural services, along with all ES, by the relative contribution of relevant ecological structures and functions and by applicable social evaluation approaches. This perspective provides a foundation for merging ecological and social science epistemologies to define and integrate cultural services better within the broader ES framework. PMID:22615401

Be meek or be bold? A colony-level behavioural syndrome in ants

PubMed Central

Bengston, S. E.; Dornhaus, A.

2014-01-01

Consistent individual variation in animal behaviour is nearly ubiquitous and has important ecological and evolutionary implications. Additionally, suites of behavioural traits are often correlated, forming behavioural syndromes in both humans and other species. Such syndromes are often described by testing for variation in traits across commonly described dimensions (e.g. aggression and neophobia), independent of whether this variation is ecologically relevant to the focal species. Here, we use a variety of ecologically relevant behavioural traits to test for a colony-level behavioural syndrome in rock ants (Temnothorax rugatulus). Specifically, we combine field and laboratory assays to measure foraging effort, how colonies respond to different types of resources, activity level, response to threat and aggression level. We find evidence for a colony level syndrome that suggests colonies consistently differ in coping style—some are more risk-prone, whereas others are more risk-averse. Additionally, by collecting data across the North American range of this species, we show that environmental variation may affect how different populations maintain consistent variation in colony behaviour. PMID:25100691

High-volume forced diuresis with matched hydration using the RenalGuard System to prevent contrast-induced nephropathy: A meta-analysis of randomized trials.

PubMed

Shah, Rahman; Wood, Sarah J; Khan, Sajjad A; Chaudhry, Amina; Rehan Khan, M; Morsy, Mohamed S

2017-12-01

Contrast-induced nephropathy (CIN) is a well-recognized complication of coronary angiography that is associated with poor outcomes. Several small randomized controlled trials (RCTs) have recently shown that in patients with chronic kidney disease (CKD), furosemide-induced forced diuresis with matched hydration using the RenalGuard system can prevent its occurrence. However, individual studies have been underpowered and thus cannot show significant differences in major clinical endpoints. Forced diuresis with matched hydration using the RenalGuard system improves clinical outcomes in patients undergoing coronary angiography. Scientific databases and websites were searched for relevant RCTs. The pooled risk ratios were calculated using random-effects models. The primary endpoint was CIN, and the secondary endpoints were major adverse clinical events (MACEs) and the need for renal replacement therapy. Data from 3 trials including 586 patients were analyzed. High-volume forced diuresis with matched hydration using the RenalGuard system decreased risk of CIN by 60% (risk ratio: 0.40, 95% confidence interval: 0.25 to 0.65, P < 0.001), MACE rate by 59%, and the need for renal replacement therapy by 78%, compared with the standard of care. In patients with CKD undergoing coronary angiography, high-volume forced diuresis with matched hydration using the RenalGuard system significantly reduces the risk of CIN, MACE rate, and the need for renal replacement therapy. Larger RCTs with sufficient power are needed to confirm these findings. © 2017 Wiley Periodicals, Inc.

The Design of Phase II Clinical Trials Testing Cancer Therapeutics: Consensus Recommendations from the Clinical Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee

PubMed Central

Seymour, Lesley; Ivy, S. Percy; Sargent, Daniel; Spriggs, David; Baker, Laurence; Rubinstein, Larry; Ratain, Mark J; Le Blanc, Michael; Stewart, David; Crowley, John; Groshen, Susan; Humphrey, Jeffrey S; West, Pamela; Berry, Donald

2010-01-01

The optimal design of phase II studies continues to be the subject of vigorous debate, especially with regards to studies of newer molecularly targeted agents. The observations that many new therapeutics ‘fail’ in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials further emphasizes the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force(CTD-TF)of the NCI Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on Phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations regarding aspects of phase II trial design which are the subject of frequent debate such as endpoints(response vs. progression free survival), randomization(single arm designs vs. randomization), inclusion of biomarkers, biomarker based patient enrichment strategies, and statistical design(e.g. two stage designs vs. multiple-group adaptive designs). While these recommendations in general encourage the use of progression-free survival as the primary endpoint, the use of randomization, the inclusion of biomarkers and the incorporation of newer designs, we acknowledge that objective response as an endpoint, and single arm designs, remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on the characteristic specific to the situation. PMID:20215557

Multicenter Randomized Controlled Trial on Duration of Therapy for Thrombosis in Children and Young Adults (Kids-DOTT): Pilot/Feasibility Phase Findings

PubMed Central

Goldenberg, N.A.; Abshire, T.; Blatchford, P.J.; Fenton, L.Z.; Halperin, J.L.; Hiatt, W.R.; Kessler, C.M.; Kittelson, J.M.; Manco-Johnson, M.J.; Spyropoulos, A.C.; Steg, P.G.; Stence, N.V.; Turpie, A.G.G.; Schulman, S.

2015-01-01

BACKGROUND Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. RESULTS No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (κ-statistic=0.75; 95% confidence interval [CI] 0.48–1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3–11.5%) and 1.4% (0.03–7.4%). CONCLUSIONS The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. PMID:26118944

Assessment of cosmetic ingredients in the in vitro reconstructed human epidermis test method EpiSkin™ using HPLC/UPLC-spectrophotometry in the MTT-reduction assay.

PubMed

Alépée, N; Hibatallah, J; Klaric, M; Mewes, K R; Pfannenbecker, U; McNamee, P

2016-06-01

Cosmetics Europe recently established HPLC/UPLC-spectrophotometry as a suitable alternative endpoint detection system for measurement of formazan in the MTT-reduction assay of reconstructed human tissue test methods irrespective of the test system involved. This addressed a known limitation for such test methods that use optical density for measurement of formazan and may be incompatible for evaluation of strong MTT reducer and/or coloured chemicals. To build on the original project, Cosmetics Europe has undertaken a second study that focuses on evaluation of chemicals with functionalities relevant to cosmetic products. Such chemicals were primarily identified from the Scientific Committee on Consumer Safety (SCCS) 2010 memorandum (addendum) on the in vitro test EpiSkin™ for skin irritation testing. Fifty test items were evaluated in which both standard photometry and HPLC/UPLC-spectrophotometry were used for endpoint detection. The results obtained in this study: 1) provide further support for Within Laboratory Reproducibility of HPLC-UPLC-spectrophotometry for measurement of formazan; 2) demonstrate, through use a case study with Basazol C Blue pr. 8056, that HPLC/UPLC-spectrophotometry enables determination of an in vitro classification even when this is not possible using standard photometry and 3) addresses the question raised by SCCS in their 2010 memorandum (addendum) to consider an endpoint detection system not involving optical density quantification in in vitro reconstructed human epidermis skin irritation test methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quality Matters: Systematic Analysis of Endpoints Related to “Cellular Life” in Vitro Data of Radiofrequency Electromagnetic Field Exposure

PubMed Central

Simkó, Myrtill; Remondini, Daniel; Zeni, Olga; Scarfi, Maria Rosaria

2016-01-01

Possible hazardous effects of radiofrequency electromagnetic fields (RF-EMF) at low exposure levels are controversially discussed due to inconsistent study findings. Therefore, the main focus of the present study is to detect if any statistical association exists between RF-EMF and cellular responses, considering cell proliferation and apoptosis endpoints separately and with both combined as a group of “cellular life” to increase the statistical power of the analysis. We searched for publications regarding RF-EMF in vitro studies in the PubMed database for the period 1995–2014 and extracted the data to the relevant parameters, such as cell culture type, frequency, exposure duration, SAR, and five exposure-related quality criteria. These parameters were used for an association study with the experimental outcome in terms of the defined endpoints. We identified 104 published articles, from which 483 different experiments were extracted and analyzed. Cellular responses after exposure to RF-EMF were significantly associated to cell lines rather than to primary cells. No other experimental parameter was significantly associated with cellular responses. A highly significant negative association with exposure condition-quality and cellular responses was detected, showing that the more the quality criteria requirements were satisfied, the smaller the number of detected cellular responses. According to our knowledge, this is the first systematic analysis of specific RF-EMF bio-effects in association to exposure quality, highlighting the need for more stringent quality procedures for the exposure conditions. PMID:27420084

Depressive symptoms and outcomes in patients with heart failure: data from the COACH study.

PubMed

Lesman-Leegte, Ivonne; van Veldhuisen, Dirk J; Hillege, Hans L; Moser, Debra; Sanderman, Robbert; Jaarsma, Tiny

2009-12-01

To study the prognostic value of depressive symptoms on heart failure (HF) readmission and mortality, in a large and clinically relevant population of hospitalized HF patients adjusted for disease severity by B-type natriuretic peptide (BNP) level. We studied 958 patients enrolled after hospitalization for HF; 37% female; mean age 71 +/- 11 years; New York Heart Association class II (51%) or III/IV (49%). Left ventricular ejection fraction: 33% +/- 14%, and median BNP level: 454 pg/mL (75% CI, 195-876 pg/mL). In total, 377 patients (39%) had depressive symptoms [Centre for Epidemiological Studies Depression Scale (CES-D) score >or=16] and 200 (21%) had severe depressive symptoms (score >or=24). During 18 months of follow-up, 386 (40%) patients reached the primary endpoint of death or readmission for HF. In multivariate analyses, CES-D was significantly associated with the primary endpoint [hazard ratio (HR) 1.13, P = 0.02], and also with both individual components of the primary endpoint [HF readmission (HR 1.165, P = 0.02) and mortality (HR 1.169, P = 0.02)]. Patients with severe depressive symptoms had a >40% higher risk for HF readmission or death. In patients with HF, depression is independently associated with poor outcomes. These findings highlight the need for continued exploration of whether improvements in depression lead to better cardiovascular outcomes. The study was registered at clinical trial (www.trialregister.nl): NCT 98675639.

Multimodal representation of limb endpoint position in the posterior parietal cortex.

PubMed

Shi, Ying; Apker, Gregory; Buneo, Christopher A

2013-04-01

Understanding the neural representation of limb position is important for comprehending the control of limb movements and the maintenance of body schema, as well as for the development of neuroprosthetic systems designed to replace lost limb function. Multiple subcortical and cortical areas contribute to this representation, but its multimodal basis has largely been ignored. Regarding the parietal cortex, previous results suggest that visual information about arm position is not strongly represented in area 5, although these results were obtained under conditions in which animals were not using their arms to interact with objects in their environment, which could have affected the relative weighting of relevant sensory signals. Here we examined the multimodal basis of limb position in the superior parietal lobule (SPL) as monkeys reached to and actively maintained their arm position at multiple locations in a frontal plane. On half of the trials both visual and nonvisual feedback of the endpoint of the arm were available, while on the other trials visual feedback was withheld. Many neurons were tuned to arm position, while a smaller number were modulated by the presence/absence of visual feedback. Visual modulation generally took the form of a decrease in both firing rate and variability with limb vision and was associated with more accurate decoding of position at the population level under these conditions. These findings support a multimodal representation of limb endpoint position in the SPL but suggest that visual signals are relatively weakly represented in this area, and only at the population level.

[In Process Citation].

PubMed

2015-01-01

The encyclical letter of Papa Francesco on an integral ecology (with its universal, not religious or catholic approach to the theme) includes a very comprehensive "care" of the world. It appears to be of specific interest and relevance for an innovative understanding of the role of the nursing profession, which crosses also frequently the fragile victims of the violations of the "human ecology", and which is called to be among the actors of active promotion of fundamental rights to life.

Information and research: an essential partnership

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oen, C.J.; White, M.G.; Dunaway, P.B.

Information support is provided to the Nevada Applied Ecology Group (NAEG) through the Ecological Sciences Information Center (ESIC) at Oak Ridge National Laboratory to offer an effective, easy-to-use link between the individual researcher and the literature relevant to his work. Information within the interest areas defined by NAEG administration is identified and entered into a computerized system that provides rapid, accurate retrieval. The primary topics are the environmental aspects of the transuranic elements. (auth)

Multiple micro-predators controlling bacterial communities in the environment.

PubMed

Johnke, Julia; Cohen, Yossi; de Leeuw, Marina; Kushmaro, Ariel; Jurkevitch, Edouard; Chatzinotas, Antonis

2014-06-01

Predator-prey interactions are a main issue in ecological theory, including multispecies predator-prey relationships and intraguild predation. This knowledge is mainly based on the study of plants and animals, while its relevance for microorganisms is not well understood. The three key groups of micro-predators include protists, predatory bacteria and bacteriophages. They greatly differ in size, in prey specificity, in hunting strategies and in the resulting population dynamics. Yet, their potential to jointly control bacterial populations and reducing biomass in complex environments such as wastewater treatment plants is vast. Here, we present relevant ecological concepts and recent findings on micropredators, and propose that an integrative approach to predation at the microscale should be developed enabling the exploitation of this potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

Protected areas as social-ecological systems: perspectives from resilience and social-ecological systems theory.

PubMed

Cumming, Graeme S; Allen, Craig R

2017-09-01

Conservation biology and applied ecology increasingly recognize that natural resource management is both an outcome and a driver of social, economic, and ecological dynamics. Protected areas offer a fundamental approach to conserving ecosystems, but they are also social-ecological systems whose ecological management and sustainability are heavily influenced by people. This editorial, and the papers in the invited feature that it introduces, discuss three emerging themes in social-ecological systems approaches to understanding protected areas: (1) the resilience and sustainability of protected areas, including analyses of their internal dynamics, their effectiveness, and the resilience of the landscapes within which they occur; (2) the relevance of spatial context and scale for protected areas, including such factors as geographic connectivity, context, exchanges between protected areas and their surrounding landscapes, and scale dependency in the provision of ecosystem services; and (3) efforts to reframe what protected areas are and how they both define and are defined by the relationships of people and nature. These emerging themes have the potential to transform management and policy approaches for protected areas and have important implications for conservation, in both theory and practice. © 2017 by the Ecological Society of America.

Threshold concepts: implications for the management of natural resources

USGS Publications Warehouse

Guntenspergen, Glenn R.; Gross, John

2014-01-01

Threshold concepts can have broad relevance in natural resource management. However, the concept of ecological thresholds has not been widely incorporated or adopted in management goals. This largely stems from the uncertainty revolving around threshold levels and the post hoc analyses that have generally been used to identify them. Natural resource managers have a need for new tools and approaches that will help them assess the existence and detection of conditions that demand management actions. Recognition of additional threshold concepts include: utility thresholds (which are based on human values about ecological systems) and decision thresholds (which reflect management objectives and values and include ecological knowledge about a system) as well as ecological thresholds. All of these concepts provide a framework for considering the use of threshold concepts in natural resource decision making.

Telemonitoring in heart failure: Big Brother watching over you.

PubMed

Dierckx, R; Pellicori, P; Cleland, J G F; Clark, A L

2015-01-01

Heart failure (HF) is a leading cause of hospitalisations in older people. Several strategies, supported by novel technologies, are now available to monitor patients' health from a distance. Although studies have suggested that remote monitoring may reduce HF hospitalisations and mortality, the study of different patient populations, the use of different monitoring technologies and the use of different endpoints limit the generalisability of the results of the clinical trials reported, so far. In this review, we discuss the existing home monitoring modalities, relevant trials and focus on future directions for telemonitoring.

Using Wetlands to Teach Ecology & Environmental Awareness in General Biology.

ERIC Educational Resources Information Center

O'Neal, Lyman H.

1995-01-01

Presents advantages of using wetlands educationally and their relevance to local, national, and global environmental issues. Discusses field trips to mangrove forests and freshwater marshes. (Author/MKR)

Phase 3 randomised study of the proposed biosimilar adalimumab GP2017 in psoriasis - impact of multiple switches.

PubMed

Blauvelt, A; Lacour, J-P; Fowler, J F; Weinberg, J M; Gospodinov, D; Schuck, E; Jauch-Lembach, J; Balfour, A; Leonardi, C L

2018-06-19

The impact of multiple switches between GP2017 and reference adalimumab (ref-ADMB) was assessed following the demonstration of equivalent efficacy and similar safety and immunogenicity, in adult patients with active, clinically stable, moderate-to-severe plaque psoriasis. This 51-week double-blinded, phase 3 study randomly assigned patients to GP2017 (N=231) or ref-ADMB (N=234) 80 mg subcutaneously at Week 0, then 40 mg biweekly from Week 1. At Week 17, patients were re-randomised to switch (n=126) or continue (n=253) treatment. Primary endpoint: patients achieving Psoriasis Area and Severity Index (PASI)75 at Week 16 (equivalence confirmed if the 95% confidence interval [CI] for the difference in PASI75 between treatments was ±18%). Key secondary endpoint: change from baseline to Week 16 in continuous PASI. Other endpoints: PASI over time, PASI 50/75/90/100, pharmacokinetics, safety, tolerability and immunogenicity for the switched and continued treatment groups. Equivalent efficacy between GP2017 and ref-ADMB was confirmed for the primary (66.8% and 65.0%, respectively; 95% CI, -7.46, 11.15) and key secondary (-60.7% and -61.5%, respectively; 95% CI, -3.15, 4.84) endpoints. PASI improved over time and was similar between treatment groups at Week 16, and the switched/continued groups from Weeks 17-51. There were no relevant safety or immunogenicity differences between GP2017 and ref-ADMB at Week 16, or the switched/continued groups from Weeks 17-51. No hypersensitivity to adalimumab was reported upon switching. Following the demonstration of GP2017 biosimilarity to ref-ADMB, switching up to four times between GP2017 and ref-ADMB had no detectable impact on efficacy, safety or immunogenicity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.