Comparison and Limitations of DVH-Based NTCP Models Derived From 3D-CRT and IMRT Data for Prediction of Gastrointestinal Toxicities in Prostate Cancer Patients by Using Propensity Score Matched Pair Analysis

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

Troeller, Almut; Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-Universität, Munich; Yan, Di, E-mail: dyan@beaumont.edu

2015-02-01

Purpose: This study compared normal tissue complication probability (NTCP) modeling of chronic gastrointestinal toxicities following prostate cancer treatment for 2 treatment modalities. Possible factors causing discrepancies in optimal NTCP model parameters between 3-dimensional conformal radiation therapy (3D-CRT) and intensity modulated RT (IMRT) were analyzed and discussed, including the impact of patient characteristics, image guidance, toxicity scoring bias, and NTCP model limitations. Methods and Materials: Rectal wall dose-volume histograms of 1115 patients treated for prostate cancer under an adaptive radiation therapy protocol were used to model gastrointestinal toxicity grade ≥2 (according to Common Terminology Criteria for Adverse Events). A total ofmore » 457 patients were treated with 3D-CRT and 658 with IMRT. 3D-CRT patients were matched to IMRT patients based on various patient characteristics, using a propensity score–based algorithm. Parameters of the Lyman equivalent uniform dose and cut-off dose logistic regression NTCP models were estimated for the 2 matched treatment modalities and the combined group. Results: After they were matched, the 3D-CRT and IMRT groups contained 275 and 550 patients with a large discrepancy of 28.7% versus 7.8% toxicities, respectively (P<.001). For both NTCP models, optimal parameters found for the 3D-CRT groups did not fit the IMRT patients well and vice versa. Models developed for the combined data overestimated NTCP for the IMRT patients and underestimated NTCP for the 3D-CRT group. Conclusions: Our analysis did not reveal a single definitive cause for discrepancies of model parameters between 3D-CRT and IMRT. Patient characteristics and bias in toxicity scoring, as well as image guidance alone, are unlikely causes of the large discrepancy of toxicities. Whether the cause was inherent to the specific NTCP models used in this study needs to be verified by future investigations. Because IMRT is increasingly

Influence of sediment chemistry and sediment toxicity on macroinvertebrate communities across 99 wadable streams of the Midwestern USA

USGS Publications Warehouse

Moran, Patrick W.; Nowell, Lisa H.; Kemble, Nile E.; Mahler, Barbara J.; Waite, Ian R.; Van Metre, Peter C.

2017-01-01

Simultaneous assessment of sediment chemistry, sediment toxicity, and macroinvertebrate communities can provide multiple lines of evidence when investigating relations between sediment contaminants and ecological degradation. These three measures were evaluated at 99 wadable stream sites across 11 states in the Midwestern United States during the summer of 2013 to assess sediment pollution across a large agricultural landscape. This evaluation considers an extensive suite of sediment chemistry totaling 274 analytes (polycyclic aromatic hydrocarbons, organochlorine compounds, polychlorinated biphenyls, polybrominated diphenyl ethers, trace elements, and current-use pesticides) and a mixture assessment based on the ratios of detected compounds to available effects-based benchmarks. The sediments were tested for toxicity with the amphipod Hyalella azteca (28-d exposure), the midge Chironomus dilutus (10-d), and, at a few sites, with the freshwater mussel Lampsilis siliquoidea (28-d). Sediment concentrations, normalized to organic carbon content, infrequently exceeded benchmarks for aquatic health, which was generally consistent with low rates of observed toxicity. However, the benchmark-based mixture score and the pyrethroid insecticide bifenthrin were significantly related to observed sediment toxicity. The sediment mixture score and bifenthrin were also significant predictors of the upper limits of several univariate measures of the macroinvertebrate community (EPT percent, MMI (Macroinvertebrate Multimetric Index) Score, Ephemeroptera and Trichoptera richness) using quantile regression. Multivariate pattern matching (Mantel-like tests) of macroinvertebrate species per site to identified contaminant metrics and sediment toxicity also indicate that the sediment mixture score and bifenthrin have weak, albeit significant, influence on the observed invertebrate community composition. Together, these three lines of evidence (toxicity tests, univariate metrics, and

Regulatory considerations in the design of comparative observational studies using propensity scores.

PubMed

Yue, Lilly Q

2012-01-01

In the evaluation of medical products, including drugs, biological products, and medical devices, comparative observational studies could play an important role when properly conducted randomized, well-controlled clinical trials are infeasible due to ethical or practical reasons. However, various biases could be introduced at every stage and into every aspect of the observational study, and consequently the interpretation of the resulting statistical inference would be of concern. While there do exist statistical techniques for addressing some of the challenging issues, often based on propensity score methodology, these statistical tools probably have not been as widely employed in prospectively designing observational studies as they should be. There are also times when they are implemented in an unscientific manner, such as performing propensity score model selection for a dataset involving outcome data in the same dataset, so that the integrity of observational study design and the interpretability of outcome analysis results could be compromised. In this paper, regulatory considerations on prospective study design using propensity scores are shared and illustrated with hypothetical examples.

Web based scoring is useful for validation and harmonisation of scoring criteria within RENEB.

PubMed

Romm, Horst; Ainsbury, Elizabeth A; Barquinero, Joan Francesc; Barrios, Leonardo; Beinke, Christina; Cucu, Alexandra; Domene, Mercedes Moreno; Filippi, Silvia; Monteiro Gil, Octávia; Gregoire, Eric; Hadjidekova, Valeria; Hatzi, Vasia; Lindholm, Carita; M Kacher, Radhia; Montoro, Alegria; Moquet, Jayne; Noditi, Mihaela; Oestreicher, Ursula; Palitti, Fabrizio; Pantelias, Gabriel; Prieto, María Jesús; Popescu, Irina; Rothkamm, Kai; Sebastià, Natividad; Sommer, Sylwester; Terzoudi, Georgia; Testa, Antonella; Wojcik, Andrzej

2017-01-01

To establish a training data set of digital images and to investigate the scoring criteria and dose assessment of the dicentric assay within the European network of biodosimetry (RENEB), a web based scoring inter-comparison was undertaken by 17 RENEB partners. Two sets of 50 high resolution images were uploaded onto the RENEB website. One set included metaphases after a moderate exposure (1.3 Gy) and the other set consisted of metaphases after a high dose exposure (3.5 Gy). The laboratories used their own calibration curves for estimating doses based on observed aberration frequencies. The dose estimations and 95% confidence limits were compared to the actual doses and the corresponding z-values were satisfactory for the majority; only the dose estimations from two laboratories were too low or too high. The coefficients of variation were 17.6% for the moderate and 11.2% for the high dose. Metaphases with controversial results could be identified for training purposes. Overall, the web based scoring of the two galleries by the 17 laboratories produced very good results. Application of web based scoring for the dicentric assay may therefore be a relevant strategy for an operational biodosimetry assistance network.

Generalizing observational study results: applying propensity score methods to complex surveys.

PubMed

Dugoff, Eva H; Schuler, Megan; Stuart, Elizabeth A

2014-02-01

To provide a tutorial for using propensity score methods with complex survey data. Simulated data and the 2008 Medical Expenditure Panel Survey. Using simulation, we compared the following methods for estimating the treatment effect: a naïve estimate (ignoring both survey weights and propensity scores), survey weighting, propensity score methods (nearest neighbor matching, weighting, and subclassification), and propensity score methods in combination with survey weighting. Methods are compared in terms of bias and 95 percent confidence interval coverage. In Example 2, we used these methods to estimate the effect on health care spending of having a generalist versus a specialist as a usual source of care. In general, combining a propensity score method and survey weighting is necessary to achieve unbiased treatment effect estimates that are generalizable to the original survey target population. Propensity score methods are an essential tool for addressing confounding in observational studies. Ignoring survey weights may lead to results that are not generalizable to the survey target population. This paper clarifies the appropriate inferences for different propensity score methods and suggests guidelines for selecting an appropriate propensity score method based on a researcher's goal. © Health Research and Educational Trust.

Evaluation of inter-observer agreement when using a clinical respiratory scoring system in pre-weaned dairy calves.

PubMed

Buczinski, S; Faure, C; Jolivet, S; Abdallah, A

2016-07-01

To determine inter-observer agreement for a clinical scoring system for the detection of bovine respiratory disease complex in calves, and the impact of classification of calves as sick or healthy based on different cut-off values. Two third-year veterinary students (Observer 1 and 2) and one post-graduate student (Observer 3) received 4 hours of training on scoring dairy calves for signs of respiratory disease, including rectal temperature, cough, eye and nasal discharge, and ear position. Observers 1 and 2 scored 40 pre-weaning dairy calves 24 hours apart (80 observations) over three visits to a calf-rearing facility, and Observers 1, 2 and 3 scored 20 calves on one visit. Inter-observer agreement was assessed using percentage of agreement (PA) and Kappa statistics for individual clinical signs, comparing Observers 1 and 2. Agreement between the three observers for total clinical score was assessed using cut-off values of ≥4, ≥5 and ≥6 to indicate unhealthy calves. Inter-observer PA for rectal temperature was 0.68, for cough 0.78, for nasal discharge 0.62, for eye discharge 0.63, and for ear position 0.85. Kappa values for all clinical signs indicated slight to fair agreement (<0.4), except temperature that had moderate agreement (0.6). The Fleiss' Kappa for total score, using cut-offs of ≥4, ≥5 and ≥6 to indicate unhealthy calves, was 0.35, 0.06 and 0.13, respectively, indicating slight to fair agreement. There was important inter-observer discrepancies in scoring clinical signs of respiratory disease, using relatively inexperienced observers. These disagreements may ultimately mean increased false negative or false positive diagnoses and incorrect treatment of cases. Visual assessment of clinical signs associated with bovine respiratory disease needs to be thoroughly validated when disease monitoring is based on the use of a clinical scoring system.

[Reliability and validity of the Chinese version on Comprehensive Scores for Financial Toxicity based on the patient-reported outcome measures].

PubMed

Yu, H H; Bi, X; Liu, Y Y

2017-08-10

Objective: To evaluate the reliability and validity of the Chinese version on comprehensive scores for financial toxicity (COST), based on the patient-reported outcome measures. Methods: A total of 118 cancer patients were face-to-face interviewed by well-trained investigators. Cronbach's α and Pearson correlation coefficient were used to evaluate reliability. Content validity index (CVI) and exploratory factor analysis (EFA) were used to evaluate the content validity and construct validity, respectively. Results: The Cronbach's α coefficient appeared as 0.889 for the whole questionnaire, with the results of test-retest were between 0.77 and 0.98. Scale-content validity index (S-CVI) appeared as 0.82, with item-content validity index (I-CVI) between 0.83 and 1.00. Two components were extracted from the Exploratory factor analysis, with cumulative rate as 68.04% and loading>0.60 on every item. Conclusion: The Chinese version of COST scale showed high reliability and good validity, thus can be applied to assess the financial situation in cancer patients.

Do Examinees Understand Score Reports for Alternate Methods of Scoring Computer Based Tests?

ERIC Educational Resources Information Center

Whittaker, Tiffany A.; Williams, Natasha J.; Dodd, Barbara G.

2011-01-01

This study assessed the interpretability of scaled scores based on either number correct (NC) scoring for a paper-and-pencil test or one of two methods of scoring computer-based tests: an item pattern (IP) scoring method and a method based on equated NC scoring. The equated NC scoring method for computer-based tests was proposed as an alternative…

Generalizing Observational Study Results: Applying Propensity Score Methods to Complex Surveys

PubMed Central

DuGoff, Eva H; Schuler, Megan; Stuart, Elizabeth A

2014-01-01

ObjectiveTo provide a tutorial for using propensity score methods with complex survey data. Data SourcesSimulated data and the 2008 Medical Expenditure Panel Survey. Study DesignUsing simulation, we compared the following methods for estimating the treatment effect: a naïve estimate (ignoring both survey weights and propensity scores), survey weighting, propensity score methods (nearest neighbor matching, weighting, and subclassification), and propensity score methods in combination with survey weighting. Methods are compared in terms of bias and 95 percent confidence interval coverage. In Example 2, we used these methods to estimate the effect on health care spending of having a generalist versus a specialist as a usual source of care. Principal FindingsIn general, combining a propensity score method and survey weighting is necessary to achieve unbiased treatment effect estimates that are generalizable to the original survey target population. ConclusionsPropensity score methods are an essential tool for addressing confounding in observational studies. Ignoring survey weights may lead to results that are not generalizable to the survey target population. This paper clarifies the appropriate inferences for different propensity score methods and suggests guidelines for selecting an appropriate propensity score method based on a researcher’s goal. PMID:23855598

Predictions of sediment toxicity using consensus-based freshwater sediment quality guidelines

USGS Publications Warehouse

Ingersoll, C.G.; MacDonald, D.D.; Wang, N.; Crane, J.L.; Field, L.J.; Haverland, P.S.; Kemble, N.E.; Lindskoog, R.A.; Severn, C.; Smorong, D.E.

2001-01-01

The objectives of this study were to compare approaches for evaluating the combined effects of chemical mixtures on the toxicity in field-collected sediments and to evaluate the ability of consensus-based probable effect concentrations (PECs) to predict toxicity in a freshwater database on both a national and regional geographic basis. A database was developed from 92 published reports, which included a total of 1,657 samples with high-quality matching sediment toxicity and chemistry data from across North America. The database was comprised primarily of 10- to 14-day or 28- to 42-day toxicity tests with the amphipod Hyalella azteca (designated as the HA10 or HA28 tests) and 10- to 14-day toxicity tests with the midges Chironomus tentans or C. riparius (designated as the CS10 test). Mean PEC quotients were calculated to provide an overall measure of chemical contamination and to support an evaluation of the combined effects of multiple contaminants in sediments. There was an overall increase in the incidence of toxicity with an increase in the mean quotients in all three tests. A consistent increase in the toxicity in all three tests occurred at a mean quotient > 0.5, however, the overall incidence of toxicity was greater in the HA28 test compared to the short-term tests. The longer-term tests, in which survival and growth are measured, tend to be more sensitive than the shorter-term tests, with acute to chronic ratios on the order of six indicated for H. azteca. Different patterns were observed among the various procedures used to calculate mean quotients. For example, in the HA28 test, a relatively abrupt increase in toxicity was associated with elevated polychlorinated biphenyls (PCBs) alone or with elevated polycyclic aromatic hydrocarbons (PAHs) alone, compared to the pattern of a gradual increase in toxicity observed with quotients calculated using a combination of metals, PAHs, and PCBs. These analyses indicate that the different patterns in toxicity may be

Predictive validity of the classroom strategies scale-observer form on statewide testing scores: an initial investigation.

PubMed

Reddy, Linda A; Fabiano, Gregory A; Dudek, Christopher M; Hsu, Louis

2013-12-01

The present study examined the validity of a teacher observation measure, the Classroom Strategies Scale--Observer Form (CSS), as a predictor of student performance on statewide tests of mathematics and English language arts. The CSS is a teacher practice observational measure that assesses evidence-based instructional and behavioral management practices in elementary school. A series of two-level hierarchical generalized linear models were fitted to data of a sample of 662 third- through fifth-grade students to assess whether CSS Part 2 Instructional Strategy and Behavioral Management Strategy scale discrepancy scores (i.e., ∑ |recommended frequency--frequency ratings|) predicted statewide mathematics and English language arts proficiency scores when percentage of minority students in schools was controlled. Results indicated that the Instructional Strategy scale discrepancy scores significantly predicted mathematics and English language arts proficiency scores: Relatively larger discrepancies on observer ratings of what teachers did versus what should have been done were associated with lower proficiency scores. Results offer initial evidence of the predictive validity of the CSS Part 2 Instructional Strategy discrepancy scores on student academic outcomes. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Impact of movie-based simulation training, with or without conventional verbal demonstration on observed OSPE scores in medical undergraduates: a double control study.

PubMed

Malik, Samina; Zaheer, Reema; Bilal, Muhammad

2013-01-01

Movie-based simulation training may be useful in delivering the preclinical observed OSPE curriculum, minimising the need of subjects/patients: however, a double-control trial needs to be performed and optimal timing and duration of training is yet to be defined. Likewise, gender-based response and students' feedback has to be assessed. The objective of this study was to compare the movie-based and traditional verbal demonstration teaching methodologies. Second-year medical undergraduates (n = 90) of Avicenna Medical College were randomised to movie-based simulation training (group B, n = 30), traditional verbal training alone (group C, n=30), and a combination (group A, n = 30). The scores were marked by observers using a standardised key and were compared for performance at 2 observed OSPE stations. Group B and A performed significantly better than group C on station 1 and 2. Gender factor did not seem to influence the score. A total of 99% students reported that combination of the 2 teaching modes is the best option. They believed it offers more clear understanding with interest (61%), long term memory (21%), use of both senses; seeing & hearing (10%) & better focus of attention (3%). Even half an hour of movie-based simulation training with traditional instructor-based training may improve student performance significantly, and the students prefer a combination of the both.

Non-localization and localization ROC analyses using clinically based scoring

NASA Astrophysics Data System (ADS)

Paquerault, Sophie; Samuelson, Frank W.; Myers, Kyle J.; Smith, Robert C.

2009-02-01

We are investigating the potential for differences in study conclusions when assessing the estimated impact of a computer-aided detection (CAD) system on readers' performance. The data utilized in this investigation were derived from a multi-reader multi-case observer study involving one hundred mammographic background images to which fixed-size and fixed-intensity Gaussian signals were added, generating a low- and high-intensity signal sets. The study setting allowed CAD assessment in two situations: when CAD sensitivity was 1) superior or 2) lower than the average reader. Seven readers were asked to review each set in the unaided and CAD-aided reading modes, mark and rate their findings. Using this data, we studied the effect on study conclusion of three clinically-based receiver operating characteristic (ROC) scoring definitions. These scoring definitions included both location-specific and non-location-specific rules. The results showed agreement in the estimated impact of CAD on the overall reader performance. In the study setting where CAD sensitivity is superior to the average reader, the mean difference in AUC between the CAD-aided read and unaided read was 0.049 (95%CIs: -0.027; 0.130) for the image scoring definition that is based on non-location-specific rules, and 0.104 (95%CIs: 0.036; 0.174) and 0.090 (95%CIs: 0.031; 0.155) for image scoring definitions that are based on location-specific rules. The increases in AUC were statistically significant for the location-specific scoring definitions. It was further observed that the variance on these estimates was reduced when using the location-specific scoring definitions compared to that using a non-location-specific scoring definition. In the study setting where CAD sensitivity is equivalent or lower than the average reader, the mean differences in AUC are slightly above 0.01 for all image scoring definitions. These increases in AUC were not statistical significant for any of the image scoring definitions

A toxicity-based method for evaluating safety of reclaimed water for environmental reuses.

PubMed

Xu, Jianying; Zhao, Chuntao; Wei, Dongbin; Du, Yuguo

2014-10-01

A large quantity of toxic chemical pollutants possibly remains in reclaimed water due to the limited removal efficiency in traditional reclamation processes. It is not enough to guarantee the safety of reclaimed water using conventional water quality criteria. An integrated assessment method based on toxicity test is necessary to vividly depict the safety of reclaimed water for reuse. A toxicity test battery consisting of lethality, genotoxicity and endocrine disrupting effect was designed to screen the multiple biological effects of residual toxic chemicals in reclaimed water. The toxicity results of reclaimed water were converted into the equivalent concentrations of the corresponding positive reference substances (EQC). Simultaneously, the predicted no-effect concentration (PNEC) of each positive reference substance was obtained by analyzing the species sensitivity distribution (SSD) of toxicity data. An index "toxicity score" was proposed and valued as 1, 2, 3, or 4 depending on the ratio of the corresponding EQC to PNEC. For vividly ranking the safety of reclaimed water, an integrated assessment index "toxicity rank" was proposed, which was classified into A, B, C, or D rank with A being the safest. The proposed method was proved to be effective in evaluating reclaimed water samples in case studies. Copyright © 2014. Published by Elsevier B.V.

Some Conceptual Issues in Observed-Score Equating

ERIC Educational Resources Information Center

van der Linden, Wim J.

2013-01-01

In spite of all of the technical progress in observed-score equating, several of the more conceptual aspects of the process still are not well understood. As a result, the equating literature struggles with rather complex criteria of equating, lack of a test-theoretic foundation, confusing terminology, and ad hoc analyses. A return to Lord's…

Prediction of true test scores from observed item scores and ancillary data.

PubMed

Haberman, Shelby J; Yao, Lili; Sinharay, Sandip

2015-05-01

In many educational tests which involve constructed responses, a traditional test score is obtained by adding together item scores obtained through holistic scoring by trained human raters. For example, this practice was used until 2008 in the case of GRE(®) General Analytical Writing and until 2009 in the case of TOEFL(®) iBT Writing. With use of natural language processing, it is possible to obtain additional information concerning item responses from computer programs such as e-rater(®). In addition, available information relevant to examinee performance may include scores on related tests. We suggest application of standard results from classical test theory to the available data to obtain best linear predictors of true traditional test scores. In performing such analysis, we require estimation of variances and covariances of measurement errors, a task which can be quite difficult in the case of tests with limited numbers of items and with multiple measurements per item. As a consequence, a new estimation method is suggested based on samples of examinees who have taken an assessment more than once. Such samples are typically not random samples of the general population of examinees, so that we apply statistical adjustment methods to obtain the needed estimated variances and covariances of measurement errors. To examine practical implications of the suggested methods of analysis, applications are made to GRE General Analytical Writing and TOEFL iBT Writing. Results obtained indicate that substantial improvements are possible both in terms of reliability of scoring and in terms of assessment reliability. © 2015 The British Psychological Society.

Measuring financial toxicity as a clinically relevant patient-reported outcome: The validation of the COmprehensive Score for financial Toxicity (COST).

PubMed

de Souza, Jonas A; Yap, Bonnie J; Wroblewski, Kristen; Blinder, Victoria; Araújo, Fabiana S; Hlubocky, Fay J; Nicholas, Lauren H; O'Connor, Jeremy M; Brockstein, Bruce; Ratain, Mark J; Daugherty, Christopher K; Cella, David

2017-02-01

Cancer and its treatment lead to increased financial distress for patients. To the authors' knowledge, to date, no standardized patient-reported outcome measure has been validated to assess this distress. Patients with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were recruited. Financial toxicity was measured by the COmprehensive Score for financial Toxicity (COST) measure. The authors collected data regarding patient characteristics, clinical trial participation, health care use, willingness to discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and health-related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy: General (FACT-G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires. Test-retest reliability, internal consistency, and validity of the COST measure were assessed using standard-scale construction techniques. Associations between the resulting factors and other variables were assessed using multivariable analyses. A total of 375 patients with advanced cancer were approached, 233 of whom (62.1%) agreed to participate. The COST measure demonstrated high internal consistency and test-retest reliability. Factor analyses revealed a coherent, single, latent variable (financial toxicity). COST values were found to be correlated with income (correlation coefficient [r] = 0.28; P<.001), psychosocial distress (r = -0.26; P<.001), and HRQOL, as measured by the FACT-G (r = 0.42; P<.001) and by the EORTC QOL instruments (r = 0.33; P<.001). Independent factors found to be associated with financial toxicity were race (P = .04), employment status (P<.001), income (P = .003), number of inpatient admissions (P = .01), and psychological distress (P = .003). Willingness to discuss costs was not found to be associated with the degree of financial distress (P = .49). The COST measure demonstrated reliability and

Malingering in Toxic Exposure. Classification Accuracy of Reliable Digit Span and WAIS-III Digit Span Scaled Scores

ERIC Educational Resources Information Center

Greve, Kevin W.; Springer, Steven; Bianchini, Kevin J.; Black, F. William; Heinly, Matthew T.; Love, Jeffrey M.; Swift, Douglas A.; Ciota, Megan A.

2007-01-01

This study examined the sensitivity and false-positive error rate of reliable digit span (RDS) and the WAIS-III Digit Span (DS) scaled score in persons alleging toxic exposure and determined whether error rates differed from published rates in traumatic brain injury (TBI) and chronic pain (CP). Data were obtained from the files of 123 persons…

Asymptotic Standard Errors of Observed-Score Equating with Polytomous IRT Models

ERIC Educational Resources Information Center

Andersson, Björn

2016-01-01

In observed-score equipercentile equating, the goal is to make scores on two scales or tests measuring the same construct comparable by matching the percentiles of the respective score distributions. If the tests consist of different items with multiple categories for each item, a suitable model for the responses is a polytomous item response…

[Evaluation of Brodifacoum-induced Toxicity by Metabonomics Approach Based on HPLC-TOF-MS].

PubMed

Yan, H; Zhuo, X Y; Shen, B H; Xiang, P; Shen, M

2017-06-01

To analyse the metabolic changes in urine of rats with brodifacoum intoxication, and to reveal the molecular mechanism of brodifacoum-induced toxicity on rats. By establishing a brodifacoum poisoning rats model, the urine metabolic profiling data of rats were acquired using high performance liquid chromatography-time of flight mass spectrometry （HPLC-TOF-MS）. The orthogonal partial least squares analysis-discrimination analysis （OPLS-DA） was applied for the multivariate statistics and the discovery of differential metabolites closely related to toxicity of brodifacoum. OPLS-DA score plot showed that the urinary metabolic at different time points before and after drug administration had good similarity within time period and presented clustering phenomenon. Comparing the urine samples of rats before drug administration with which after drug administration, twenty-two metabolites related to brodifacoum-induced toxicity were selected. The toxic effect of brodifacoum worked by disturbing the metabolic pathways in rats such as tricarboxylic cycle, glycolysis, sphingolipid metabolism and tryptophan metabolism, and the toxicity of brodifacoum is characterized of accumulation effect. The metabonomic method based on urine HPLC-TOF-MS can provide a novel insight into the study on molecular mechanism of brodifacoum-induced toxicity. Copyright© by the Editorial Department of Journal of Forensic Medicine

Wastewater toxicity of tannin- versus chromium-based leather tanneries in Marrakesh, Morocco.

PubMed

De Nicola, E; Meriç, S; Della Rocca, C; Gallo, M; Iaccarino, M; Manini, P; Petruzzelli, D; Belgiorno, V; Cheggour, M; Di Gennaro, A; Moukrim, A; Tünay, O; Pagano, G

2007-10-01

The toxicity of leather tanning wastewater from a traditional tannery (TT), which is based on vegetable tannin (VT), was compared with wastewater from a tannery combining the use of chromium-based tanning (CT) with VT-based tanning operations. Wastewater samples from a TT and a CT plant as well as from five sewer sampling points were collected in Marrakesh, Morocco, and the concentrations of VT and some selected inorganics were measured. A set of bioassays were used to test wastewater toxicity in sea urchin (Paracentrotus lividus) embryos and sperm, in Daphnia magna, and in marine microalgae (Dunaliella tertiolecta). Toxicity end points included: (1) developmental defects, embryonic mortality, sperm fertilization success, and offspring damage in sea urchins; (2) D. magna immobilization; and (3) algal growth rate inhibition. Toxicity tests on TT and CT effluents (TTE and CTE) were run at dilutions ranging from 0.1% to 2% (sea urchins and algae) or up to 12% in D. magna. Parallel bioassays were run on VT extract (VTE) at nominal tannin concentrations ranging from 0.1 to 10 mg l(-1). The results showed higher toxicity of CTE compared with TTE. CTE toxicity in sea urchins and algae showed concentration-related trends, whereas TTE exerted hormetic effects at levels of 0.1% to 0.2% and toxic effects at levels >or=1%. The same trends were observed for VTE, suggesting a prevailing role of tannin in TTE-associated effects. The moderate wastewater toxicity of VT-based tanneries might prompt interest in the VT tanning process.

Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

PubMed

Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

2017-02-01

Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

The potential ecotoxicological impact of pharmaceutical and personal care products on humans and freshwater, based on USEtox™ characterization factors. A Spanish case study of toxicity impact scores.

PubMed

Ortiz de García, Sheyla; García-Encina, Pedro A; Irusta-Mata, Rubén

2017-12-31

Pharmaceutical and personal care products (PPCPs) are being increasingly included in Life Cycle Assessment studies (LCAs) since they have brought into evidence both human and ecological adverse effects due to their presence in different environmental compartments, wastewater facilities and industry. Therefore, the main goal of this research was to estimate the characterization factors (CFs) of 27 PPCPs widely used worldwide in order to incorporate their values into Life Cycle Impact Assessment studies (LCIA) or to generate a toxicity impact score ranking. Physicochemical properties, degradation rates, bioaccumulation, ecotoxicity and human health effects were collected from experimental data, recognized databases or estimated using EPI Suite™ and the USEtox™ software, and were subsequently used for estimating CFs. In addition, a Spanish toxicity impact score ranking was carried out for 49 PPCPs using the 27 newly calculated CFs, and 22 CFs already available in the literature, besides the data related to the occurrence of PPCPs in the environment in Spain. It has been highlighted that emissions into the continental freshwater compartment showed the highest CFs values for human effects (ranging from 10 -9 to 10 -3 Cases·kg -1 ), followed by emissions into the air (10 -9 to 10 -5 Cases·kg -1 ), soil (10 -11 to 10 5 Cases·kg -1 ) and seawater (10 -12 to 10 -4 Cases·kg -1 ). CFs regarding the affectation of freshwater aquatic environments were the highest of those proceeding from emissions into continental freshwater (between 1 to 10 4 PAF·m 3 ·day·kg emission -1 ) due to the direct contact between the source of emission and the compartment affected, followed by soil (among 10 -1 to 10 4 PAF·m 3 ·day·kg emission -1 ), and air (among 10 -2 to 10 4 PAF·m 3 ·day·kg emission -1 ) while the lowest were the CFs of continental seawater (among 10 -28 to 10 -3 PAF·m 3 ·day·kg emission -1 ). Freshwater aquatic ecotoxicological CFs are much higher than human

Propensity score analysis with partially observed covariates: How should multiple imputation be used?

PubMed

Leyrat, Clémence; Seaman, Shaun R; White, Ian R; Douglas, Ian; Smeeth, Liam; Kim, Joseph; Resche-Rigon, Matthieu; Carpenter, James R; Williamson, Elizabeth J

2017-01-01

Inverse probability of treatment weighting is a popular propensity score-based approach to estimate marginal treatment effects in observational studies at risk of confounding bias. A major issue when estimating the propensity score is the presence of partially observed covariates. Multiple imputation is a natural approach to handle missing data on covariates: covariates are imputed and a propensity score analysis is performed in each imputed dataset to estimate the treatment effect. The treatment effect estimates from each imputed dataset are then combined to obtain an overall estimate. We call this method MIte. However, an alternative approach has been proposed, in which the propensity scores are combined across the imputed datasets (MIps). Therefore, there are remaining uncertainties about how to implement multiple imputation for propensity score analysis: (a) should we apply Rubin's rules to the inverse probability of treatment weighting treatment effect estimates or to the propensity score estimates themselves? (b) does the outcome have to be included in the imputation model? (c) how should we estimate the variance of the inverse probability of treatment weighting estimator after multiple imputation? We studied the consistency and balancing properties of the MIte and MIps estimators and performed a simulation study to empirically assess their performance for the analysis of a binary outcome. We also compared the performance of these methods to complete case analysis and the missingness pattern approach, which uses a different propensity score model for each pattern of missingness, and a third multiple imputation approach in which the propensity score parameters are combined rather than the propensity scores themselves (MIpar). Under a missing at random mechanism, complete case and missingness pattern analyses were biased in most cases for estimating the marginal treatment effect, whereas multiple imputation approaches were approximately unbiased as long as the

Evaluation of Two Methods for Modeling Measurement Errors When Testing Interaction Effects with Observed Composite Scores

ERIC Educational Resources Information Center

Hsiao, Yu-Yu; Kwok, Oi-Man; Lai, Mark H. C.

2018-01-01

Path models with observed composites based on multiple items (e.g., mean or sum score of the items) are commonly used to test interaction effects. Under this practice, researchers generally assume that the observed composites are measured without errors. In this study, we reviewed and evaluated two alternative methods within the structural…

Cellular toxicity of TiO2-based nanofilaments.

PubMed

Magrez, Arnaud; Horváth, Lenke; Smajda, Rita; Salicio, Valérie; Pasquier, Nathalie; Forró, László; Schwaller, Beat

2009-08-25

At present, nanofilaments are not exclusively based on carbon atoms but can be produced from many inorganic materials in the form of nanotubes and nanowires. It is essential to systematically assess the acute toxicity of these newly synthesized materials since it cannot be predicted from the known toxicity of the same material in another form. Here, the cellular toxicity of TiO2-based nanofilaments was studied in relation to their morphology and surface chemistry. These structures produced by hydrothermal treatment were titanate nanotubes and nanowires with a Na(x)TiO(2+delta) composition. The cytotoxic effect was mainly evaluated by MTT assays combined with direct cell counting and cytopathological analyses of the lung tumor cells. Our work clearly demonstrated that the presence of Na(x)TiO(2+delta) nanofilaments had a strong dose-dependent effect on cell proliferation and cell death. Nanofilament internalization and alterations in cell morphology were observed. Acid treatment performed to substitute Na(+) with H(+) in the Na(x)TiO(2+delta) nanofilaments strongly enhanced the cytotoxic action. This effect was attributed to structural imperfections, which are left by the atom diffusion during the substitution. On the basis of our findings, we conclude that TiO2-based nanofilaments are cytotoxic and thus precautions should be taken during their manipulation.

Electronic Medical Record-Based Radiation Oncology Toxicity Recording Instrument Aids Benchmarking and Quality Improvement in the Clinic.

PubMed

Albuquerque, Kevin; Rodgers, Kellie; Spangler, Ann; Rahimi, Asal; Willett, DuWayne

2018-03-01

The on-treatment visit (OTV) for radiation oncology is essential for patient management. Radiation toxicities recorded during the OTV may be inconsistent because of the use of free text and the lack of treatment site-specific templates. We developed a radiation oncology toxicity recording instrument (ROTOX) in a health system electronic medical record (EMR). Our aims were to assess improvement in documentation of toxicities and to develop clinic toxicity benchmarks. A ROTOX that was based on National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) with flow-sheet functionality was developed in the EMR. Improvement in documentation was assessed at various time intervals. High-grade toxicities (ie, grade ≥ 3 by CTCAE) by site were audited to develop benchmarks and to track nursing and physician actions taken in response to these. A random sample of OTV notes from each clinic physician before ROTOX implementation was reviewed and assigned a numerical document quality score (DQS) that was based on completeness and comprehensiveness of toxicity grading. The mean DQS improved from an initial level of 41% to 99% (of the maximum possible DQS) when resampled at 6 months post-ROTOX. This high-level DQS was maintained 3 years after ROTOX implementation at 96% of the maximum. For months 7 to 9 after implementation (during a 3-month period), toxicity grading was recorded in 4,443 OTVs for 698 unique patients; 107 episodes of high-grade toxicity were identified during this period, and toxicity-specific intervention was documented in 95%. An EMR-based ROTOX enables consistent recording of treatment toxicity. In a uniform sample of patients, local population toxicity benchmarks can be developed, and clinic response can be tracked.

Observed-Score Equating as a Test Assembly Problem.

ERIC Educational Resources Information Center

van der Linden, Wim J.; Luecht, Richard M.

1998-01-01

Derives a set of linear conditions of item-response functions that guarantees identical observed-score distributions on two test forms. The conditions can be added as constraints to a linear programming model for test assembly. An example illustrates the use of the model for an item pool from the Law School Admissions Test (LSAT). (SLD)

Chi-square-based scoring function for categorization of MEDLINE citations.

PubMed

Kastrin, A; Peterlin, B; Hristovski, D

2010-01-01

Text categorization has been used in biomedical informatics for identifying documents containing relevant topics of interest. We developed a simple method that uses a chi-square-based scoring function to determine the likelihood of MEDLINE citations containing genetic relevant topic. Our procedure requires construction of a genetic and a nongenetic domain document corpus. We used MeSH descriptors assigned to MEDLINE citations for this categorization task. We compared frequencies of MeSH descriptors between two corpora applying chi-square test. A MeSH descriptor was considered to be a positive indicator if its relative observed frequency in the genetic domain corpus was greater than its relative observed frequency in the nongenetic domain corpus. The output of the proposed method is a list of scores for all the citations, with the highest score given to those citations containing MeSH descriptors typical for the genetic domain. Validation was done on a set of 734 manually annotated MEDLINE citations. It achieved predictive accuracy of 0.87 with 0.69 recall and 0.64 precision. We evaluated the method by comparing it to three machine-learning algorithms (support vector machines, decision trees, naïve Bayes). Although the differences were not statistically significantly different, results showed that our chi-square scoring performs as good as compared machine-learning algorithms. We suggest that the chi-square scoring is an effective solution to help categorize MEDLINE citations. The algorithm is implemented in the BITOLA literature-based discovery support system as a preprocessor for gene symbol disambiguation process.

Improving Factor Score Estimation Through the Use of Observed Background Characteristics

PubMed Central

Curran, Patrick J.; Cole, Veronica; Bauer, Daniel J.; Hussong, Andrea M.; Gottfredson, Nisha

2016-01-01

A challenge facing nearly all studies in the psychological sciences is how to best combine multiple items into a valid and reliable score to be used in subsequent modelling. The most ubiquitous method is to compute a mean of items, but more contemporary approaches use various forms of latent score estimation. Regardless of approach, outside of large-scale testing applications, scoring models rarely include background characteristics to improve score quality. The current paper used a Monte Carlo simulation design to study score quality for different psychometric models that did and did not include covariates across levels of sample size, number of items, and degree of measurement invariance. The inclusion of covariates improved score quality for nearly all design factors, and in no case did the covariates degrade score quality relative to not considering the influences at all. Results suggest that the inclusion of observed covariates can improve factor score estimation. PMID:28757790

Preequating with Empirical Item Characteristic Curves: An Observed-Score Preequating Method

ERIC Educational Resources Information Center

Zu, Jiyun; Puhan, Gautam

2014-01-01

Preequating is in demand because it reduces score reporting time. In this article, we evaluated an observed-score preequating method: the empirical item characteristic curve (EICC) method, which makes preequating without item response theory (IRT) possible. EICC preequating results were compared with a criterion equating and with IRT true-score…

Numeric Estimates of Teratogenic Severity from Embryo-Fetal Developmental Toxicity Studies.

PubMed

Wise, L David

2016-02-01

A developing organism exposed to a toxicant will have a response that ranges from none to severe (i.e., death or malformation). The response at a given dosage may be termed teratogenic (or developmental toxic) severity and is dependent on exposure conditions. Prenatal/embryo-fetal developmental (EFD) toxicity studies in rodents and rabbits are the most consistent and definitive assessments of teratogenic severity, and teratogenesis screening assays are best validated against their results. A formula is presented that estimates teratogenic severity for each group, including control, within an EFD study. The developmental components include embryonic/fetal death, malformations, variations, and mean fetal weight. The contribution of maternal toxicity is included with multiplication factors to adjust for the extent of mortality, maternal body weight change, and other parameters deemed important. The derivation of the formula to calculate teratogenic severity is described. Various EFD data sets from the literature are presented to highlight considerations to the calculation of the various components of the formula. Each score is compared to the concurrent control group to obtain a relative teratogenic severity. The limited studies presented suggest relative scores of two- to scores ≥ fivefold higher than control have increasingly more severe teratogenicity. Such scores may help refine the concept of an exposure-based validation list for use by proponents of screening assays (Daston et al., 2014) by estimating the severity of "positive" exposures, or in other situations by defining the severity of a LOAEL (lowest observed adverse effect level). © 2016 Wiley Periodicals, Inc.

Relationships of Measurement Error and Prediction Error in Observed-Score Regression

ERIC Educational Resources Information Center

Moses, Tim

2012-01-01

The focus of this paper is assessing the impact of measurement errors on the prediction error of an observed-score regression. Measures are presented and described for decomposing the linear regression's prediction error variance into parts attributable to the true score variance and the error variances of the dependent variable and the predictor…

Influence of S. mutans on base-metal dental casting alloy toxicity.

PubMed

McGinley, E L; Dowling, A H; Moran, G P; Fleming, G J P

2013-01-01

We have highlighted that exposure of base-metal dental casting alloys to the acidogenic bacterium Streptococcus mutans significantly increases cellular toxicity following exposure to immortalized human TR146 oral keratinocytes. With Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), S. mutans-treated nickel-based (Ni-based) and cobalt-chromium-based (Co-Cr-based) dental casting alloys were shown to leach elevated levels of metal ions compared with untreated dental casting alloys. We targeted several biological parameters: cell morphology, viable cell counts, cell metabolic activity, cell toxicity, and inflammatory cytokine expression. S. mutans-treated dental casting alloys disrupted cell morphology, elicited significantly decreased viable cell counts (p < 0.0001) and cell metabolic activity (p < 0.0001), and significantly increased cell toxicity (p < 0.0001) and inflammatory cytokine expression (p < 0.0001). S. mutans-treated Ni-based dental casting alloys induced elevated levels of cellular toxicity compared with S. mutans-treated Co-Cr-based dental casting alloys. While our findings indicated that the exacerbated release of metal ions from S. mutans-treated base-metal dental casting alloys was the likely result of the pH reduction during S. mutans growth, the exact nature of mechanisms leading to accelerated dissolution of alloy-discs is not yet fully understood. Given the predominance of S. mutans oral carriage and the exacerbated cytotoxicity observed in TR146 cells following exposure to S. mutans-treated base-metal dental casting alloys, the implications for the long-term stability of base-metal dental restorations in the oral cavity are a cause for concern.

Computerized In Vitro Test for Chemical Toxicity Based on Tetrahymena Swimming Patterns

NASA Technical Reports Server (NTRS)

Noever, David A.; Matsos, Helen C.; Cronise, Raymond J.; Looger, Loren L.; Relwani, Rachna A.; Johnson, Jacqueline U.

1994-01-01

An apparatus and a method for rapidly determining chemical toxicity have been evaluated as an alternative to the rabbit eye initancy test (Draize). The toxicity monitor includes an automated scoring of how motile biological cells (Tetrahymena pyriformis) slow down or otherwise change their swimming patterns in a hostile chemical environment. The method, called the motility assay (MA), is tested for 30 s to determine the chemical toxicity in 20 aqueous samples containing trace organics and salts. With equal or better detection limits, results compare favorably to in vivo animal tests of eye irritancy.

Congenital heart surgery: expected versus observed surgical performance according to the Aristotle complexity score.

PubMed

Photiadis, J; Sinzobahamvya, N; Arenz, C; Sata, S; Haun, C; Schindler, E; Asfour, B; Hraska, V

2011-08-01

The Aristotle score quantifies the complexity involved in congenital heart surgery. It defines surgical performance as complexity score times hospital survival. We studied how expected and observed surgical performance evolved over time. 2312 main procedures carried out between 2006 and 2010 were analyzed. The Aristotle basic score, corresponding hospital survival and related observed surgical performance were estimated. Expected survival was based on the mortality risks published by O'Brien and coauthors. Observed performance divided by expected performance was called the standardized ratio of performance. This should trend towards a figure above 100%. Survival rates and performance are given with 95% confidence intervals. The mean Aristotle basic score was 7.88 ± 2.68. 51 patients died: observed hospital survival was 97.8 % (97.1 %-98.3%). 115 deaths were anticipated: expected survival was 95.2% (93.5%-96.3%). Observed and expected surgical performance reached 7.71 (7.65-7.75) and 7.49 (7.37-7.59), respectively. Therefore the overall standardized ratio of performance was 102.94%. The ratio increased from 2006 (ratio = 101.60%) to 2009 (103.92%) and was 103.42% in 2010. Performance was high for the repair of congenital corrected transposition of the great arteries and ventricular septal defect (VSD) by atrial switch and Rastelli procedure, the Norwood procedure, repair of truncus arteriosus, aortic arch repair and VSD closure, and the Ross-Konno procedure, with corresponding standardized ratios of 123.30%, 116.83%, 112.99%, 110.86% and 110.38%, respectively. With a ratio of 82.87%, performance was low for repair of Ebstein's anomaly. The standardized ratio of surgical performance integrates three factors into a single value: procedure complexity, postoperative observed survival, and comparison with expected survival. It constitutes an excellent instrument for quality monitoring of congenital heart surgery programs over time. It allows an accurate comparison of

Automatically-computed prehospital severity scores are equivalent to scores based on medic documentation.

PubMed

Reisner, Andrew T; Chen, Liangyou; McKenna, Thomas M; Reifman, Jaques

2008-10-01

Prehospital severity scores can be used in routine prehospital care, mass casualty care, and military triage. If computers could reliably calculate clinical scores, new clinical and research methodologies would be possible. One obstacle is that vital signs measured automatically can be unreliable. We hypothesized that Signal Quality Indices (SQI's), computer algorithms that differentiate between reliable and unreliable monitored physiologic data, could improve the predictive power of computer-calculated scores. In a retrospective analysis of trauma casualties transported by air ambulance, we computed the Triage Revised Trauma Score (RTS) from archived travel monitor data. We compared the areas-under-the-curve (AUC's) of receiver operating characteristic curves for prediction of mortality and red blood cell transfusion for 187 subjects with comparable quantities of good-quality and poor-quality data. Vital signs deemed reliable by SQI's led to significantly more discriminatory severity scores than vital signs deemed unreliable. We also compared automatically-computed RTS (using the SQI's) versus RTS computed from vital signs documented by medics. For the subjects in whom the SQI algorithms identified 15 consecutive seconds of reliable vital signs data (n = 350), the automatically-computed scores' AUC's were the same as the medic-based scores' AUC's. Using the Prehospital Index in place of RTS led to very similar results, corroborating our findings. SQI algorithms improve automatically-computed severity scores, and automatically-computed scores using SQI's are equivalent to medic-based scores.

Scoring ligand similarity in structure-based virtual screening.

PubMed

Zavodszky, Maria I; Rohatgi, Anjali; Van Voorst, Jeffrey R; Yan, Honggao; Kuhn, Leslie A

2009-01-01

Scoring to identify high-affinity compounds remains a challenge in virtual screening. On one hand, protein-ligand scoring focuses on weighting favorable and unfavorable interactions between the two molecules. Ligand-based scoring, on the other hand, focuses on how well the shape and chemistry of each ligand candidate overlay on a three-dimensional reference ligand. Our hypothesis is that a hybrid approach, using ligand-based scoring to rank dockings selected by protein-ligand scoring, can ensure that high-ranking molecules mimic the shape and chemistry of a known ligand while also complementing the binding site. Results from applying this approach to screen nearly 70 000 National Cancer Institute (NCI) compounds for thrombin inhibitors tend to support the hypothesis. EON ligand-based ranking of docked molecules yielded the majority (4/5) of newly discovered, low to mid-micromolar inhibitors from a panel of 27 assayed compounds, whereas ranking docked compounds by protein-ligand scoring alone resulted in one new inhibitor. Since the results depend on the choice of scoring function, an analysis of properties was performed on the top-scoring docked compounds according to five different protein-ligand scoring functions, plus EON scoring using three different reference compounds. The results indicate that the choice of scoring function, even among scoring functions measuring the same types of interactions, can have an unexpectedly large effect on which compounds are chosen from screening. Furthermore, there was almost no overlap between the top-scoring compounds from protein-ligand versus ligand-based scoring, indicating the two approaches provide complementary information. Matchprint analysis, a new addition to the SLIDE (Screening Ligands by Induced-fit Docking, Efficiently) screening toolset, facilitated comparison of docked molecules' interactions with those of known inhibitors. The majority of interactions conserved among top-scoring compounds for a given scoring

Generation of GHS Scores from TEST and online sources ...

EPA Pesticide Factsheets

Alternatives assessment frameworks such as DfE (Design for the Environment) evaluate chemical alternatives in terms of human health effects, ecotoxicity, and fate. T.E.S.T. (Toxicity Estimation Software Tool) can be utilized to evaluate human health in terms of acute oral rat toxicity, developmental toxicity, endocrine activity, and mutagenicity. It can be used to evaluate ecotoxicity (in terms of acute fathead minnow toxicity) and fate (in terms of bioconcentration factor). It also be used to estimate a variety of key physicochemical properties such as melting point, boiling point, vapor pressure, water solubility, and bioconcentration factor. A web-based version of T.E.S.T. is currently being developed to allow predictions to be made from other web tools. Online data sources such as from NCCT’s Chemistry Dashboard, REACH dossiers, or from ChemHat.org can also be utilized to obtain GHS (Global Harmonization System) scores for comparing alternatives. The purpose of this talk is to show how GHS (Global Harmonization Score) data can be obtained from literature sources and from T.E.S.T. (Toxicity Estimation Software Tool). This data will be used to compare chemical alternatives in the alternatives assessment dashboard (a 2018 CSS product).

An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies

ERIC Educational Resources Information Center

Austin, Peter C.

2011-01-01

The propensity score is the probability of treatment assignment conditional on observed baseline characteristics. The propensity score allows one to design and analyze an observational (nonrandomized) study so that it mimics some of the particular characteristics of a randomized controlled trial. In particular, the propensity score is a balancing…

Computerized in vitro test for chemical toxicity based on tetrahymena swimming patterns

NASA Technical Reports Server (NTRS)

Noever, David A.; Matsos, Helen C.; Cronise, Raymond J.; Looger, Loren L.; Relwani, Rachna A.; Johnson, Jacqueline U.

1994-01-01

An apparatus and method for rapidly determining chemical toxicity was evaluated. The toxicity monitor includes an automated scoring of how motile biological cells (Tetrahymena pyriformis) slow down or otherwise change their swimming patterns in a hostile chemical environment. The device, called the Motility Assay Apparatus (MAA) is tested for 30 second determination of chemical toxicity in 20 aqueous samples containing trace organics and salts. With equal or better detection limits, results compare favorably to in vivo animal tests of eye irritancy, in addition to agreeing for all chemicals with previous manual evaluations of single cell motility.

Balancing Score Adjusted Targeted Minimum Loss-based Estimation

PubMed Central

Lendle, Samuel David; Fireman, Bruce; van der Laan, Mark J.

2015-01-01

Adjusting for a balancing score is sufficient for bias reduction when estimating causal effects including the average treatment effect and effect among the treated. Estimators that adjust for the propensity score in a nonparametric way, such as matching on an estimate of the propensity score, can be consistent when the estimated propensity score is not consistent for the true propensity score but converges to some other balancing score. We call this property the balancing score property, and discuss a class of estimators that have this property. We introduce a targeted minimum loss-based estimator (TMLE) for a treatment-specific mean with the balancing score property that is additionally locally efficient and doubly robust. We investigate the new estimator’s performance relative to other estimators, including another TMLE, a propensity score matching estimator, an inverse probability of treatment weighted estimator, and a regression-based estimator in simulation studies. PMID:26561539

Influence of container adsorption upon observed pyrethroid toxicity to Ceriodaphnia dubia and Hyalella azteca

PubMed Central

Wheelock, Craig E.; Miller, Jeff L.; Miller, Mike J.; Phillips, Bryn M.; Gee, Shirley J.; Tjeerdema, Ronald S.; Hammock, Bruce D.

2006-01-01

Pyrethroid insecticides are known for their potential toxicity to aquatic invertebrates and many fish species. A significant problem in the study of pyrethroid toxicity is their extreme hydrophobicity. They can adsorb to test container surfaces and many studies, therefore, report pyrethroid levels as nominal water concentrations. In this study, pyrethroid adsorption to sampling and test containers was measured and several container treatments were examined for their ability to decrease pyrethroid adsorption. None of the chemical treatments were successful at preventing pyrethroid loss from aqueous samples, but vortexing of containers served to resuspend pyrethroids. The effects of the observed adsorption on Ceriodaphnia dubia and Hyalella azteca permethrin toxicity were examined. Species-specific results showed a time-dependent decrease in toxicity following pyrethroid adsorption to test containers for C. dubia, but not for H. azteca. These results demonstrate that pyrethroid adsorption to containers can significantly affect the observed outcome in toxicity-testing and serves as a caution for researchers and testing laboratories. PMID:15951033

Should predictive scores based on vital signs be used in the same way as those based on laboratory data? A hypothesis generating retrospective evaluation of in-hospital mortality by four different scoring systems.

PubMed

Kellett, John; Murray, Alan

2016-05-01

few studies have compared the discrimination of predictive scores of in-hospital mortality that used vital signs with those using laboratory results in different patient populations. a hypothesis generating retrospective observational cohort study. A score that only used vital signs was compared with three other scores that used laboratory changes in 44,985 medical and 20,432 surgical patients. the discrimination of the score based only on vital signs was highest for the prediction of in-hospital death within 24h. In contrast the, albeit lower, discrimination of scores based only on laboratory data remained constant for the prediction of death up to 30 days after hospital admission. Moreover, the discrimination of scores based only on laboratory data was higher in surgical than in medical patients. in acutely ill medical patients a vital sign based score appears to predict mortality within 24h better than scores using laboratory data. This may be because in acutely ill patients vital sign changes indicate how well a patient is responding to a current insult. In contrast, for patients without acute illness laboratory data may be a more valuable indication of the patient's capacity to respond to insults in the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Autism Diagnostic Observation Schedule, Toddler Module: Standardized Severity Scores

PubMed Central

Esler, Amy N.; Bal, Vanessa Hus; Guthrie, Whitney; Wetherby, Amy; Weismer, Susan Ellis; Lord, Catherine

2016-01-01

Standardized calibrated severity scores (CSS) have been created for Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) Modules 1–4 as a metric of the relative severity of autism-specific behaviors. Total and domain CSS were created for the Toddler Module to facilitate comparison to other modules. Analyses included 388 children with ASD age 12 to 30 months and were replicated on 435 repeated assessments from 127 children with ASD. Compared to raw scores, associations between total and domain CSS and participant characteristics were reduced in the original sample. Verbal IQ effects on Social Affect-CSS were not reduced in the replication sample. Toddler Module CSS increases comparability of ADOS-2 scores across modules and allows studies of symptom trajectories to extend to earlier ages. PMID:25832801

Environmental and health impacts of fine and ultrafine metallic particles: assessment of threat scores.

PubMed

Goix, Sylvaine; Lévêque, Thibaut; Xiong, Tian-Tian; Schreck, Eva; Baeza-Squiban, Armelle; Geret, Florence; Uzu, Gaëlle; Austruy, Annabelle; Dumat, Camille

2014-08-01

This study proposes global threat scores to prioritize the harmfulness of anthropogenic fine and ultrafine metallic particles (FMP) emitted into the atmosphere at the global scale. (Eco)toxicity of physicochemically characterized FMP oxides for metals currently observed in the atmosphere (CdO, CuO, PbO, PbSO(4), Sb(2)O(3), and ZnO) was assessed by performing complementary in vitro tests: ecotoxicity, human bioaccessibility, cytotoxicity, and oxidative potential. Using an innovative methodology based on the combination of (eco)toxicity and physicochemical results, the following hazard classification of the particles is proposed: CdCl2~CdO>CuO>PbO>ZnO>PbSO(4)>Sb(2)O(3). Both cadmium compounds exhibited the highest threat score due to their high cytotoxicity and bioaccessible dose, whatever their solubility and speciation, suggesting that cadmium toxicity is due to its chemical form rather than its physical form. In contrast, the Sb(2)O(3) threat score was the lowest due to particles with low specific area and solubility, with no effects except a slight oxidative stress. As FMP physicochemical properties reveal differences in specific area, crystallization systems, dissolution process, and speciation, various mechanisms may influence their biological impact. Finally, this newly developed and global approach could be widely used in various contexts of pollution by complex metal particles and may improve risk management. Copyright © 2014 Elsevier Inc. All rights reserved.

Modeling late rectal toxicities based on a parameterized representation of the 3D dose distribution

NASA Astrophysics Data System (ADS)

Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Partridge, Mike

2011-04-01

Many models exist for predicting toxicities based on dose-volume histograms (DVHs) or dose-surface histograms (DSHs). This approach has several drawbacks as firstly the reduction of the dose distribution to a histogram results in the loss of spatial information and secondly the bins of the histograms are highly correlated with each other. Furthermore, some of the complex nonlinear models proposed in the past lack a direct physical interpretation and the ability to predict probabilities rather than binary outcomes. We propose a parameterized representation of the 3D distribution of the dose to the rectal wall which explicitly includes geometrical information in the form of the eccentricity of the dose distribution as well as its lateral and longitudinal extent. We use a nonlinear kernel-based probabilistic model to predict late rectal toxicity based on the parameterized dose distribution and assessed its predictive power using data from the MRC RT01 trial (ISCTRN 47772397). The endpoints under consideration were rectal bleeding, loose stools, and a global toxicity score. We extract simple rules identifying 3D dose patterns related to a specifically low risk of complication. Normal tissue complication probability (NTCP) models based on parameterized representations of geometrical and volumetric measures resulted in areas under the curve (AUCs) of 0.66, 0.63 and 0.67 for predicting rectal bleeding, loose stools and global toxicity, respectively. In comparison, NTCP models based on standard DVHs performed worse and resulted in AUCs of 0.59 for all three endpoints. In conclusion, we have presented low-dimensional, interpretable and nonlinear NTCP models based on the parameterized representation of the dose to the rectal wall. These models had a higher predictive power than models based on standard DVHs and their low dimensionality allowed for the identification of 3D dose patterns related to a low risk of complication.

The Kernel Levine Equipercentile Observed-Score Equating Function. Research Report. ETS RR-13-38

ERIC Educational Resources Information Center

von Davier, Alina A.; Chen, Haiwen

2013-01-01

In the framework of the observed-score equating methods for the nonequivalent groups with anchor test design, there are 3 fundamentally different ways of using the information provided by the anchor scores to equate the scores of a new form to those of an old form. One method uses the anchor scores as a conditioning variable, such as the Tucker…

Propensity Score-Based Methods versus MTE-Based Methods in Causal Inference: Identification, Estimation, and Application

ERIC Educational Resources Information Center

Zhou, Xiang; Xie, Yu

2016-01-01

Since the seminal introduction of the propensity score (PS) by Rosenbaum and Rubin, PS-based methods have been widely used for drawing causal inferences in the behavioral and social sciences. However, the PS approach depends on the ignorability assumption: there are no unobserved confounders once observed covariates are taken into account. For…

Timed Get Up and Go Test and Geriatric 8 Scores and the Association With (Chemo-)Radiation Therapy Noncompliance and Acute Toxicity in Elderly Cancer Patients.

PubMed

Middelburg, Judith G; Mast, Mirjam E; de Kroon, Maaike; Jobsen, Jan J; Rozema, Tom; Maas, Huub; Baartman, Elizabet A; Geijsen, Debby; van der Leest, Annija H; van den Bongard, Desirée J; van Loon, Judith; Budiharto, Tom; Coebergh, Jan Willem; Aarts, Mieke J; Struikmans, Henk

2017-07-15

To investigate whether the Geriatric 8 (G8) and the Timed Get Up and Go Test (TGUGT) and clinical and demographic patient characteristics were associated with acute toxicity of radiation therapy and noncompliance in elderly cancer patients being irradiated with curative intent. Patients were eligible if aged ≥65 years and diagnosed with breast, non-small cell lung, prostate, head and neck, rectal, or esophageal cancer, and were referred for curative radiation therapy. We recorded acute toxicity and noncompliance and identified potential predictors, including the G8 and TGUGT. We investigated 402 patients with a median age of 72 years (range, 65-96 years). According to the G8, 44.4% of the patients were frail. Toxicity grade ≥3 was observed in 22% of patients who were frail according to the G8 and 9.1% of patients who were not frail. The difference was 13% (confidence interval 5.2%-20%; P=.0006). According to the TGUGT 18.8% of the patients were frail; 21% of the frail according to the TGUGT developed toxicity grade ≥3, compared with 13% who were not frail. The difference was 7.3% (confidence interval -2.7% to 17%; P=.11). Overall compliance was 95%. Toxicity was most strongly associated with type of primary tumor, chemotherapy, age, and World Health Organization performance status. Compliance was associated with type of primary tumor and age. The usefulness of the TGUGT and G8 score in daily practice seems to be limited. Type of primary tumor, chemoradiotherapy, age, and World Health Organization performance status were more strongly associated with acute toxicity. Only chemoradiotherapy and age were associated with noncompliance. Overall the compliance was very high. To allow better-informed treatment decisions, a more accurate prediction of toxicity is desirable. Copyright © 2017. Published by Elsevier Inc.

A quantitative weight of evidence methodology for the assessment of reproductive and developmental toxicity and its application for classification and labeling of chemicals.

PubMed

Dekant, Wolfgang; Bridges, James

2016-12-01

Hazard assessment of chemicals usually applies narrative assessments with a number of weaknesses. Therefore, application of weight of evidence (WoE) approaches are often mandated but guidance to perform a WoE assessment is lacking. This manuscript describes a quantitative WoE (QWoE) assessment for reproductive toxicity data and its application for classification and labeling (C&L). Because C&L criteria are based on animal studies, the scope is restricted to animal toxicity data. The QWoE methodology utilizes numerical scoring sheets to assess reliability of a publication and the toxicological relevance of reported effects. Scores are given for fourteen quality aspects, best practice receives the highest score. The relevance/effects scores (0 to four) are adjusted to the key elements of the toxic response for the endpoint and include weighting factors for effects on different levels of the biological organization. The relevance/effects scores are then assessed against the criteria dose-response, magnitude and persistence of effects, consistency of observations with the hypothesis, and relation of effects to human disease. The quality/reliability scores and the relevance/effect scores are then multiplied to give a numerical strength of evidence for adverse effects. This total score is then used to assign the chemical to the different classes employed in classification. Copyright © 2016 Elsevier Inc. All rights reserved.

Proposal for a new categorization of aseptic processing facilities based on risk assessment scores.

PubMed

Katayama, Hirohito; Toda, Atsushi; Tokunaga, Yuji; Katoh, Shigeo

2008-01-01

Risk assessment of aseptic processing facilities was performed using two published risk assessment tools. Calculated risk scores were compared with experimental test results, including environmental monitoring and media fill run results, in three different types of facilities. The two risk assessment tools used gave a generally similar outcome. However, depending on the tool used, variations were observed in the relative scores between the facilities. For the facility yielding the lowest risk scores, the corresponding experimental test results showed no contamination, indicating that these ordinal testing methods are insufficient to evaluate this kind of facility. A conventional facility having acceptable aseptic processing lines gave relatively high risk scores. The facility showing a rather high risk score demonstrated the usefulness of conventional microbiological test methods. Considering the significant gaps observed in calculated risk scores and in the ordinal microbiological test results between advanced and conventional facilities, we propose a facility categorization based on risk assessment. The most important risk factor in aseptic processing is human intervention. When human intervention is eliminated from the process by advanced hardware design, the aseptic processing facility can be classified into a new risk category that is better suited for assuring sterility based on a new set of criteria rather than on currently used microbiological analysis. To fully benefit from advanced technologies, we propose three risk categories for these aseptic facilities.

Key physicochemical properties of nanomaterials in view of their toxicity: an exploratory systematic investigation for the example of carbon-based nanomaterial

NASA Astrophysics Data System (ADS)

Salieri, Beatrice; Pasteris, Andrea; Netkueakul, Woranan; Hischier, Roland

2017-03-01

Currently, a noncomprehensive understanding of the physicochemical properties of carbon-based nanomaterial (CBNs), which may affect toxic effects, is still observable. In this study, an exploratory systematic investigation into the key physicochemical properties of multiwall carbon nanotube (MWCNT), single-wall carbon nanotube (SWCNT), and C60-fullerene on their ecotoxicity has been undertaken. We undertook an extensive survey of the literature pertaining to the ecotoxicity of organism representative of the trophic level of algae, crustaceans, and fish. Based on this, a set of data reporting both the physicochemical properties of carbon-based nanomaterial and the observed toxic effect has been established. The relationship between physicochemical properties and observed toxic effect was investigated based on various statistical approaches. Specifically, analysis of variance by one-way ANOVA was used to assess the effect of categorical properties (use of a dispersant or treatments in the test medium, type of carbon-based nanomaterial, i.e., SWCNT, MWCNT, C60-fullerene, functionalization), while multiple regression analysis was used to assess the effect of quantitative properties (i.e., diameter length of nanotubes, secondary size) on the toxicity values. The here described investigations revealed significant relationships among the physicochemical properties and observed toxic effects. The research was mainly affected by the low availability of data and also by the low variability of the studies collected. Overall, our results demonstrate that the here proposed and applied approach could have a major role in identifying the physicochemical properties of relevance for the toxicity of nanomaterial. However, the future success of the approach would require that the ENMs and the experimental conditions used in the toxicity studies are fully characterized.

Observation Versus Embolization in Patients with Blunt Splenic Injury After Trauma: A Propensity Score Analysis.

PubMed

Olthof, Dominique C; Joosse, Pieter; Bossuyt, Patrick M M; de Rooij, Philippe P; Leenen, Loek P H; Wendt, Klaus W; Bloemers, Frank W; Goslings, J Carel

2016-05-01

Non-operative management (NOM) is the standard of care in hemodynamically stable patients with blunt splenic injury after trauma. Splenic artery embolization (SAE) is reported to increase observation success rate. Studies demonstrating improved splenic salvage rates with SAE primarily compared SAE with historical controls. The aim of this study was to investigate whether SAE improves success rate compared to observation alone in contemporaneous patients with blunt splenic injury. We included adult patients with blunt splenic injury admitted to five Level 1 Trauma Centers between January 2009 and December 2012 and selected for NOM. Successful treatment was defined as splenic salvage and no splenic re-intervention. We calculated propensity scores, expressing the probability of undergoing SAE, using multivariable logistic regression and created five strata based on the quintiles of the propensity score distribution. A weighted relative risk (RR) was calculated across strata to express the chances of success with SAE. Two hundred and six patients were included in the study. Treatment was successful in 180 patients: 134/146 (92 %) patients treated with observation and 48/57 (84 %) patients treated with SAE. The weighted RR for success with SAE was 1.17 (0.94-1.45); for complications, the weighted RR was 0.71 (0.41-1.22). The mean number of transfused blood products was 4.4 (SD 9.9) in the observation group versus 9.1 (SD 17.2) in the SAE group. After correction for confounders with propensity score stratification technique, there was no significant difference between embolization and observation alone with regard to successful treatment in patients with blunt splenic injury after trauma.

Resident training for eclampsia and magnesium toxicity management: simulation or traditional lecture?

PubMed

Fisher, Nelli; Bernstein, Peter S; Satin, Andrew; Pardanani, Setul; Heo, Hye; Merkatz, Irwin R; Goffman, Dena

2010-10-01

To compare eclampsia and magnesium toxicity management among residents randomly assigned to lecture or simulation-based education. Statified by year, residents (n = 38) were randomly assigned to 3 educational intervention groups: Simulation→Lecture, Simulation, and Lecture. Postintervention simulations were performed for all and scored using standardized lists. Maternal, fetal, eclampsia management, and magnesium toxcity scores were assigned. Mann-Whitney U, Wilcoxon rank sum and χ(2) tests were used for analysis. Postintervention maternal (16 and 15 vs 12; P < .05) and eclampsia (19 vs 16; P < .05) scores were significantly better in simulation based compared with lecture groups. Postintervention magnesium toxcitiy and fetal scores were not different among groups. Lecture added to simulation did not lead to incremental benefit when eclampsia scores were compared between Simulation→Lecture and Simulation (19 vs 19; P = nonsignificant). Simulation training is superior to traditional lecture alone for teaching crucial skills for the optimal management of both eclampsia and magnesium toxicity, 2 life-threatening obstetric emergencies. Published by Mosby, Inc.

Comparative toxicity of two glyphosate-based formulations to Eisenia andrei under laboratory conditions.

PubMed

Piola, Lucas; Fuchs, Julio; Oneto, María Luisa; Basack, Silvana; Kesten, Eva; Casabé, Norma

2013-04-01

Glyphosate-based products are the leading post-emergent agricultural herbicides in the world, particularly in association with glyphosate tolerant crops. However, studies on the effects of glyphosate-based formulations on terrestrial receptors are scarce. This study was conducted to evaluate the comparative toxicity of two glyphosate-based products: Roundup FG (monoammonium salt, 72% acid equivalent, glyphosate-A) and Mon 8750 (monoammonium salt, 85.4% acid equivalent, glyphosate-B), towards the earthworm Eisenia andrei. Median lethal concentration (LC50) showed that glyphosate-A was 4.5-fold more toxic than glyphosate-B. Sublethal concentrations caused a concentration-dependent weight loss, consistent with the reported effect of glyphosate as uncoupler of oxidative phosphorylation. Glyphosate-A showed deleterious effects on DNA and lysosomal damage at concentrations close to the applied environmental concentrations (14.4 μg ae cm(-2)). With glyphosate-B toxic effects were observed at higher doses, close to its LC50, suggesting that the higher toxicity of formulate A could be attributed to the effects of some of the so-called "inert ingredients", either due to a direct intrinsic toxicity, or to an enhancement in the bioavailability and/or bioaccumulation of the active ingredient. Our results highlight the importance of ecotoxicological assessment not only of the active ingredients, but also of the different formulations usually employed in agricultural practices. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improved scores for observed teamwork in the clinical environment following a multidisciplinary operating room simulation intervention.

PubMed

Weller, Jennifer M; Cumin, David; Civil, Ian D; Torrie, Jane; Garden, Alexander; MacCormick, Andrew D; Gurusinghe, Nishanthi; Boyd, Matthew J; Frampton, Christopher; Cokorilo, Martina; Tranvik, Magnus; Carlsson, Lisa; Lee, Tracey; Ng, Wai Leap; Crossan, Michael; Merry, Alan F

2016-08-05

We ran a Multidisciplinary Operating Room Simulation (MORSim) course for 20 complete general surgical teams from two large metropolitan hospitals. Our goal was to improve teamwork and communication in the operating room (OR). We hypothesised that scores for teamwork and communication in the OR would improve back in the workplace following MORSim. We used an extended Behavioural Marker Risk Index (BMRI) to measure teamwork and communication, because a relationship has previously been documented between BMRI scores and surgical patient outcomes. Trained observers scored general surgical teams in the OR at the two study hospitals before and after MORSim, using the BMRI. Analysis of BMRI scores for the 224 general surgical cases before and 213 cases after MORSim showed BMRI scores improved by more than 20% (0.41 v 0.32, p<0.001). Previous research suggests that this improved teamwork score would translate into a clinically important reduction in complications and mortality in surgical patients. We demonstrated an improvement in scores for teamwork and communication in general surgical ORs following our intervention. These results support the use of simulation-based multidisciplinary team training for OR staff to promote better teamwork and communication, and potentially improve outcomes for general surgical patients.

Application of a computed tomography based cystic fibrosis scoring system to chest tomosynthesis

NASA Astrophysics Data System (ADS)

Söderman, Christina; Johnsson, Åse; Vikgren, Jenny; Rystedt, Hans; Ivarsson, Jonas; Rossi Norrlund, Rauni; Nyberg Andersson, Lena; Bâth, Magnus

2013-03-01

In the monitoring of progression of lung disease in patients with cystic fibrosis (CF), recurrent computed tomography (CT) examinations are often used. The relatively new imaging technique chest tomosynthesis (CTS) may be an interesting alternative in the follow-up of these patients due to its visualization of the chest in slices at radiation doses and costs significantly lower than is the case with CT. A first step towards introducing CTS imaging in the diagnostics of CF patients is to establish a scoring system appropriate for evaluating the severity of CF pulmonary disease based on findings in CTS images. Previously, several such CF scoring systems based on CT imaging have been published. The purpose of the present study was to develop a CF scoring system for CTS, by starting from an existing scoring system dedicated for CT images and making modifications regarded necessary to make it appropriate for use with CTS images. In order to determine any necessary changes, three thoracic radiologists independently used a scoring system dedicated for CT on both CT and CTS images from CF patients. The results of the scoring were jointly evaluated by all the observers, which lead to suggestions for changes to the scoring system. Suggested modifications include excluding the scoring of air trapping and doing the scoring of the findings in quadrants of the image instead of in each lung lobe.

Using propensity scores to estimate the effects of insecticides on stream invertebrates from observational data

USGS Publications Warehouse

Lester L. Yuan,; Amina I. Pollard,; Carlisle, Daren M.

2009-01-01

Analyses of observational data can provide insights into relationships between environmental conditions and biological responses across a broader range of natural conditions than experimental studies, potentially complementing insights gained from experiments. However, observational data must be analyzed carefully to minimize the likelihood that confounding variables bias observed relationships. Propensity scores provide a robust approach for controlling for the effects of measured confounding variables when analyzing observational data. Here, we use propensity scores to estimate changes in mean invertebrate taxon richness in streams that have experienced insecticide concentrations that exceed aquatic life use benchmark concentrations. A simple comparison of richness in sites exposed to elevated insecticides with those that were not exposed suggests that exposed sites had on average 6.8 fewer taxa compared to unexposed sites. The presence of potential confounding variables makes it difficult to assert a causal relationship from this simple comparison. After controlling for confounding factors using propensity scores, the difference in richness between exposed and unexposed sites was reduced to 4.1 taxa, a difference that was still statistically significant. Because the propensity score analysis controlled for the effects of a wide variety of possible confounding variables, we infer that the change in richness observed in the propensity score analysis was likely caused by insecticide exposure.

Using propensity scores to estimate the effects of insecticides on stream invertebrates from observational data

USGS Publications Warehouse

Yuan, L.L.; Pollard, A.I.; Carlisle, D.M.

2009-01-01

Analyses of observational data can provide insights into relationships between environmental conditions and biological responses across a broader range of natural conditions than experimental studies, potentially complementing insights gained from experiments. However, observational data must be analyzed carefully to minimize the likelihood that confounding variables bias observed relationships. Propensity scores provide a robust approach for controlling for the effects of measured confounding variables when analyzing observational data. Here, we use propensity scores to estimate changes in mean invertebrate taxon richness in streams that have experienced insecticide concentrations that exceed aquatic life use benchmark concentrations. A simple comparison of richness in sites exposed to elevated insecticides with those that were not exposed suggests that exposed sites had on average 6.8 fewer taxa compared to unexposed sites. The presence of potential confounding variables makes it difficult to assert a causal relationship from this simple comparison. After controlling for confounding factors using propensity scores, the difference in richness between exposed and unexposed sites was reduced to 4.1 taxa, a difference that was still statistically significant. Because the propensity score analysis controlled for the effects of a wide variety of possible confounding variables, we infer that the change in richness observed in the propensity score analysis was likely caused by insecticide exposure. ?? 2009 SETAC.

Competency based training in robotic surgery: benchmark scores for virtual reality robotic simulation.

PubMed

Raison, Nicholas; Ahmed, Kamran; Fossati, Nicola; Buffi, Nicolò; Mottrie, Alexandre; Dasgupta, Prokar; Van Der Poel, Henk

2017-05-01

To develop benchmark scores of competency for use within a competency based virtual reality (VR) robotic training curriculum. This longitudinal, observational study analysed results from nine European Association of Urology hands-on-training courses in VR simulation. In all, 223 participants ranging from novice to expert robotic surgeons completed 1565 exercises. Competency was set at 75% of the mean expert score. Benchmark scores for all general performance metrics generated by the simulator were calculated. Assessment exercises were selected by expert consensus and through learning-curve analysis. Three basic skill and two advanced skill exercises were identified. Benchmark scores based on expert performance offered viable targets for novice and intermediate trainees in robotic surgery. Novice participants met the competency standards for most basic skill exercises; however, advanced exercises were significantly more challenging. Intermediate participants performed better across the seven metrics but still did not achieve the benchmark standard in the more difficult exercises. Benchmark scores derived from expert performances offer relevant and challenging scores for trainees to achieve during VR simulation training. Objective feedback allows both participants and trainers to monitor educational progress and ensures that training remains effective. Furthermore, the well-defined goals set through benchmarking offer clear targets for trainees and enable training to move to a more efficient competency based curriculum. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Bi-Factor MIRT Observed-Score Equating for Mixed-Format Tests

ERIC Educational Resources Information Center

Lee, Guemin; Lee, Won-Chan

2016-01-01

The main purposes of this study were to develop bi-factor multidimensional item response theory (BF-MIRT) observed-score equating procedures for mixed-format tests and to investigate relative appropriateness of the proposed procedures. Using data from a large-scale testing program, three types of pseudo data sets were formulated: matched samples,…

Can Mapping Algorithms Based on Raw Scores Overestimate QALYs Gained by Treatment? A Comparison of Mappings Between the Roland-Morris Disability Questionnaire and the EQ-5D-3L Based on Raw and Differenced Score Data.

PubMed

Madan, Jason; Khan, Kamran A; Petrou, Stavros; Lamb, Sarah E

2017-05-01

Mapping algorithms are increasingly being used to predict health-utility values based on responses or scores from non-preference-based measures, thereby informing economic evaluations. We explored whether predictions in the EuroQol 5-dimension 3-level instrument (EQ-5D-3L) health-utility gains from mapping algorithms might differ if estimated using differenced versus raw scores, using the Roland-Morris Disability Questionnaire (RMQ), a widely used health status measure for low back pain, as an example. We estimated algorithms mapping within-person changes in RMQ scores to changes in EQ-5D-3L health utilities using data from two clinical trials with repeated observations. We also used logistic regression models to estimate response mapping algorithms from these data to predict within-person changes in responses to each EQ-5D-3L dimension from changes in RMQ scores. Predicted health-utility gains from these mappings were compared with predictions based on raw RMQ data. Using differenced scores reduced the predicted health-utility gain from a unit decrease in RMQ score from 0.037 (standard error [SE] 0.001) to 0.020 (SE 0.002). Analysis of response mapping data suggests that the use of differenced data reduces the predicted impact of reducing RMQ scores across EQ-5D-3L dimensions and that patients can experience health-utility gains on the EQ-5D-3L 'usual activity' dimension independent from improvements captured by the RMQ. Mappings based on raw RMQ data overestimate the EQ-5D-3L health utility gains from interventions that reduce RMQ scores. Where possible, mapping algorithms should reflect within-person changes in health outcome and be estimated from datasets containing repeated observations if they are to be used to estimate incremental health-utility gains.

The Autism Diagnostic Observation Schedule, Module 4: Revised Algorithm and Standardized Severity Scores

ERIC Educational Resources Information Center

Hus, Vanessa; Lord, Catherine

2014-01-01

The recently published Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) includes revised diagnostic algorithms and standardized severity scores for modules used to assess younger children. A revised algorithm and severity scores are not yet available for Module 4, used with verbally fluent adults. The current study revises the Module 4…

Environmental and health impacts of fine and ultrafine metallic particles: Assessment of threat scores

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

Goix, Sylvaine; UMR 5245 CNRS-INP-UPS, EcoLab; Lévêque, Thibaut

2014-08-15

This study proposes global threat scores to prioritize the harmfulness of anthropogenic fine and ultrafine metallic particles (FMP) emitted into the atmosphere at the global scale. (Eco)toxicity of physicochemically characterized FMP oxides for metals currently observed in the atmosphere (CdO, CuO, PbO, PbSO{sub 4}, Sb{sub 2}O{sub 3}, and ZnO) was assessed by performing complementary in vitro tests: ecotoxicity, human bioaccessibility, cytotoxicity, and oxidative potential. Using an innovative methodology based on the combination of (eco)toxicity and physicochemical results, the following hazard classification of the particles is proposed: CdCl{sub 2}∼CdO>CuO>PbO>ZnO>PbSO{sub 4}>Sb{sub 2}O{sub 3}. Both cadmium compounds exhibited the highest threat score duemore » to their high cytotoxicity and bioaccessible dose, whatever their solubility and speciation, suggesting that cadmium toxicity is due to its chemical form rather than its physical form. In contrast, the Sb{sub 2}O{sub 3} threat score was the lowest due to particles with low specific area and solubility, with no effects except a slight oxidative stress. As FMP physicochemical properties reveal differences in specific area, crystallization systems, dissolution process, and speciation, various mechanisms may influence their biological impact. Finally, this newly developed and global approach could be widely used in various contexts of pollution by complex metal particles and may improve risk management. - Highlights: • Seven micro- and nano- monometallic characterized particles were studied as references. • Bioaccessibility, eco and cytotoxicity, and oxidative potential assays were performed. • According to calculated threat scores: CdCl{sub 2}∼CdO>CuO>PbO>ZnO>PbSO{sub 4}>Sb{sub 2}O{sub 3}.« less

The Autism Diagnostic Observation Schedule, Toddler Module: Standardized Severity Scores

ERIC Educational Resources Information Center

Esler, Amy N.; Bal, Vanessa Hus; Guthrie, Whitney; Wetherby, Amy; Weismer, Susan Ellis; Lord, Catherine

2015-01-01

Standardized calibrated severity scores (CSS) have been created for Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) Modules 1-4 as a metric of the relative severity of autism-specific behaviors. Total and domain CSS were created for the Toddler Module to facilitate comparison to other modules. Analyses included 388 children with ASD…

Trimethoprim/sulfamethoxazole-induced phenytoin toxicity in the elderly: a population-based study

PubMed Central

Antoniou, Tony; Gomes, Tara; Mamdani, Muhammad M; Juurlink, David N

2011-01-01

AIMS Pharmacokinetic studies suggest that trimethoprim (TMP) can inhibit the hepatic metabolism of phenytoin, but the clinical relevance of this is uncertain. We studied the risk of phenytoin toxicity following the prescription of trimethoprim/sulfamethoxazole (TMP/SMX), a commonly used antibiotic, among elderly patients receiving phenytoin. METHODS We conducted a population-based, nested case–control study of a cohort of Ontario residents aged 66 years of age or older treated with phenytoin over a 17-year period (April 1 1992 to March 31 2009). Within this group, case patients were those hospitalized with phenytoin toxicity. For each case, we identified up to four control patients from the same cohort, matched for age and sex, and determined the odds ratio (OR) for the association between phenytoin toxicity and receipt of TMP/SMX in the preceding 30 days. RESULTS Among 58 429 elderly patients receiving phenytoin during the study period, we identified 796 case patients hospitalized for phenytoin toxicity and 3148 matched controls. Following multivariable adjustment for potential confounders, we observed a more than doubling of the risk of phenytoin toxicity following the receipt of TMP/SMX [adjusted OR 2.11, 95% confidence interval (CI) 1.24, 3.60]. In contrast, we observed no such risk with amoxicillin, an antibiotic with similar indications but not expected to interact with phenytoin (adjusted OR 1.12, 95% CI 0.64, 1.98). CONCLUSION Among older patients receiving phenytoin, treatment with TMP/SMX is associated with a more than twofold increase in the risk of phenytoin toxicity. When clinically appropriate, alternate antibiotics should be considered for these patients. PMID:21395647

THE FUTURE OF COMPUTER-BASED TOXICITY PREDICTION: MECHANISM-BASED MODELS VS. INFORMATION MINING APPROACHES

EPA Science Inventory

The Future of Computer-Based Toxicity Prediction:
Mechanism-Based Models vs. Information Mining Approaches

When we speak of computer-based toxicity prediction, we are generally referring to a broad array of approaches which rely primarily upon chemical structure ...

Measurement of COPD Severity Using a Survey-Based Score

PubMed Central

Omachi, Theodore A.; Katz, Patricia P.; Yelin, Edward H.; Iribarren, Carlos; Blanc, Paul D.

2010-01-01

Background: A comprehensive survey-based COPD severity score has usefulness for epidemiologic and health outcomes research. We previously developed and validated the survey-based COPD Severity Score without using lung function or other physiologic measurements. In this study, we aimed to further validate the severity score in a different COPD cohort and using a combination of patient-reported and objective physiologic measurements. Methods: Using data from the Function, Living, Outcomes, and Work cohort study of COPD, we evaluated the concurrent and predictive validity of the COPD Severity Score among 1,202 subjects. The survey instrument is a 35-point score based on symptoms, medication and oxygen use, and prior hospitalization or intubation for COPD. Subjects were systemically assessed using structured telephone survey, spirometry, and 6-min walk testing. Results: We found evidence to support concurrent validity of the score. Higher COPD Severity Score values were associated with poorer FEV1 (r = −0.38), FEV1% predicted (r = −0.40), Body mass, Obstruction, Dyspnea, Exercise Index (r = 0.57), and distance walked in 6 min (r = −0.43) (P < .0001 in all cases). Greater COPD severity was also related to poorer generic physical health status (r = −0.49) and disease-specific health-related quality of life (r = 0.57) (P < .0001). The score also demonstrated predictive validity. It was also associated with a greater prospective risk of acute exacerbation of COPD defined as ED visits (hazard ratio [HR], 1.31; 95% CI, 1.24-1.39), hospitalizations (HR, 1.59; 95% CI, 1.44-1.75), and either measure of hospital-based care for COPD (HR, 1.34; 95% CI, 1.26-1.41) (P < .0001 in all cases). Conclusion: The COPD Severity Score is a valid survey-based measure of disease-specific severity, both in terms of concurrent and predictive validity. The score is a psychometrically sound instrument for use in epidemiologic and outcomes research in COPD. PMID:20040611

Intra- and inter-observer reliability of ten major histological scoring systems used for the evaluation of in vivo cartilage repair.

PubMed

Bonasia, Davide Edoardo; Marmotti, Antongiulio; Massa, Alessandro Domenico Felice; Ferro, Andrea; Blonna, Davide; Castoldi, Filippo; Rossi, Roberto

2015-09-01

In the last two decades, many surgical techniques have been described for articular cartilage repair. Reliable histological scoring systems are fundamental tools to evaluate new procedures. Several histological scoring systems have been described, and these can be divided in elementary and comprehensive scores, according to the number of sub-items. The aim of this study was to test the inter- and intra-observer reliability of ten main scores used for the histological evaluation of in vivo cartilage repair. The authors tested the starting hypothesis that elementary scores would show superior intra- and inter-observer reliability compared with comprehensive scores. Fifty histological sections obtained from the trochlea of New Zealand Rabbit and stained with Safranin-O fast green were used. The histological sections were analysed by 4 observers: 2 experienced in cartilage histology and 2 inexperienced. Histological evaluations were performed at time 1 and time 2, separated by a 30-day interval. The following scores were used: Mankin, O'Driscoll, Pineda, Wakitani, Fortier, Selleres, ICRS, ICRSII, Oswestry (OsScore) and modified O'Driscoll. Intra- and inter-observer reliability were evaluated for each score. In addition, the pavement-ceiling effect and the Bland-Altman Coefficient of Repeatability were then evaluated for each sub-item of every score. Intra-observer reliability was high for all observers in every score, even though the reliability was significantly lower for non-expert observers compared with expert counterparts. In terms of Coefficient of Repeatability, some scores performed better (O'Driscoll, Modified O'Driscoll and ICRSII) than others (Fortier, Seller). Inter-observer reliability was high for all observers in every score, but significantly lower for non-expert compared with expert observers. In expert hands, all the scores showed high intra- and inter-observer reliability, independently of the complexity. Although every score has advantages and

Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients.

PubMed

De Meerleer, Gert; Vakaet, Luc; Meersschout, Sabine; Villeirs, Geert; Verbaeys, Antony; Oosterlinck, Wim; De Neve, Wilfried

2004-11-01

Dose escalation improves local control in prostate cancer. At Ghent University Hospital, intensity-modulated radiotherapy (IMRT) is used to increase the dose to the prostate and/or seminal vesicles. We report on acute toxicity in 114 patients who received IMRT for prostate cancer. Intensity-modulated radiotherapy was initiated after approval of our ethics committee. A class solution was used to plan all cases. Three beams (gantry 0 degrees , 116 degrees , and 244 degrees ) and anatomy-based segmentation were used to create an intensity-modulated dose distribution. Maximal rectal dose was set at 2 Gy per fraction. Detailed dose-volume histograms for all relevant structures were present. For all patients, we determined the pretreatment morbidity by a detailed preradiotherapy, in-house developed symptom scale. All patients were treated with 18 MV photons of an Elekta linear accelerator. Patients were seen on a weekly basis during treatment, and 1 month (M1) and 3 months (M3) thereafter. The registration of acute toxicity was standardized by a fixed questionnaire. The Radiation Therapy Oncology Group (RTOG) toxicity scale served as a basis, but additional symptoms, such as rectal blood loss, urgency, and incontinence, were scored as well. All 114 IMRT plans were delivered successfully without any interruption or technical problem. Daily treatment time was always less than 8 min and less than 6 min in 90% of the cases. Grade 1 and Grade 2 gastrointestinal (GI) toxicities were observed in 44% and 29% of the patients, respectively, during the whole period. If only the RTOG scale was used, Grade 1 and Grade 2 GI toxicities were noted in 39% and 27% of the patients, respectively, leaving 34% free of acute RTOG-scaled toxicity. Grade 3 genitourinary (GU) toxicity was seen in 8 patients (7%), all but 1 during treatment. Grade 2 and Grade 1 GU toxicities were seen in 36% and 47% of the patients, respectively, leaving only 10% free of acute GU toxicity. Anatomy-based IMRT to

Toxicity prediction of PHDDs and phenols in the light of nucleic acid bases and DNA base pair interaction.

PubMed

Mondal Roy, Sutapa; Roy, Debesh R; Sahoo, Suban K

2015-11-01

The applicability of Density Functional Theory (DFT) based descriptors for the development of quantitative structure-toxicity relationships (QSTR) is assessed for two different series of toxic aromatic compounds, viz., polyhalogenated dibenzo-p-dioxins (PHDDs) and phenols (PHs). A series of 20 compounds each for PHDDs and PHs with their experimental toxicities (IC50 and IGC50) is chosen in the present study to develop DFT based efficient quantum chemical parameters (QCPs) for explaining the toxin potential of the considered compounds. A systematic analysis to find out the electron donation/acceptance nature of these selected compounds with the considered model biosystems, viz., nucleic acid (NA) bases and DNA base pairs, is performed to identify potential QCPs. Accordingly, PHDDs is found to be electron acceptors whereas phenols as donors, during their interaction with biosystems. Two parameter regression model is carried out comprising global charge transfer (ΔN), and local Fukui Function's for nucleophilic attack (fk(+)) for PHDDs and the same for electrophilic attack (fk(-)) in case of PHs. It is heartening to note that our chosen descriptors, viz, charge transfer (ΔN) and Fukui Function (fk(±)) plays a crucial role by explaining more than 90% of the observed toxic behavior (in terms of correlation-coefficient, R) of PHDDs and PHs. The developed QCPs, viz., ΔN and fk(±) can be added as the new descriptors in the QSTR parlance. Copyright © 2015 Elsevier Inc. All rights reserved.

MRI target delineation may reduce long-term toxicity after prostate radiotherapy.

PubMed

Sander, Lotte; Langkilde, Niels Christian; Holmberg, Mats; Carl, Jesper

2014-06-01

Aiming for minimal toxicity after radical prostate cancer (PC) radiotherapy (RT), magnetic resonance imaging (MRI) target delineation could be a possible benefit knowing that clinical target volumes (CTV) are up to 30% smaller, when CTV delineation on MRI is compared to standard computed tomography (CT). This study compares long-term toxicity using CT or MRI delineation before PC RT. Urinary and rectal toxicity assessments 36 months after image-guided RT (78 Gy) using CTC-AE scores in two groups of PC patients. Peak symptom score values were registered. One group of patients (n=72) had standard CT target delineation and gold markers as fiducials. Another group of patients (n=73) had MRI target delineation and a nickel-titanium stent as fiducial. At 36 months no difference in overall survival (92% in both groups, p=0.29) or in PSA-relapse free survival was found between the groups (MRI=89% and CT=94%, p=0.67). A significantly smaller CTV was found in the MRI group (p=0.02). Urinary retention and frequency were significantly reduced in the MRI group (p=0.03 in the matter of both). The overall urinary and rectal toxicity did not differ between the two groups. MRI delineation leads to a significantly reduced CTV. Significantly lower urinary frequency and urinary retention toxicity scores were observed following MRI delineation. The study did not find significant differences in overall urinary or rectal toxicity between the two groups. PSA-relapse survival did not differ between the two groups at 36 months.

Does present use of cardiovascular medication reflect elevated cardiovascular risk scores estimated ten years ago? A population based longitudinal observational study

PubMed Central

2011-01-01

Background It is desirable that those at highest risk of cardiovascular disease should have priority for preventive measures, eg. treatment with prescription drugs to modify their risk. We wanted to investigate to what extent present use of cardiovascular medication (CVM) correlates with cardiovascular risk estimated by three different risk scores (Framingham, SCORE and NORRISK) ten years ago. Methods Prospective logitudinal observational study of 20 252 participants in The Hordaland Health Study born 1950-57, not using CVM in 1997-99. Prescription data obtained from The Norwegian Prescription Database in 2008. Results 26% of men and 22% of women aged 51-58 years had started to use some CVM during the previous decade. As a group, persons using CVM scored significantly higher on the risk algorithms Framingham, SCORE and NORRISK compared to those not treated. 16-20% of men and 20-22% of women with risk scores below the high-risk thresholds for the three risk scores were treated with CVM, while 60-65% of men and 25-45% of women with scores above the high-risk thresholds received no treatment. Among women using CVM, only 2.2% (NORRISK), 4.4% (SCORE) and 14.5% (Framingham) had risk scores above the high-risk values. Low education, poor self-reported general health, muscular pains, mental distress (in females only) and a family history of premature cardiovascular disease correlated with use of CVM. Elevated blood pressure was the single factor most strongly predictive of CVM treatment. Conclusion Prescription of CVM to middle-aged individuals by large seems to occur independently of estimated total cardiovascular risk, and this applies especially to females. PMID:21366925

Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG-ps) in patients receiving palliative chemotherapy for gastroesophageal cancer.

PubMed

Crumley, Andrew B C; Stuart, Robert C; McKernan, Margaret; McDonald, Alexander C; McMillan, Donald C

2008-08-01

The aim of the present study was to compare an inflammation-based prognostic score (Glasgow Prognostic Score, GPS) with performance status (ECOG-ps) in patients receiving platinum-based chemotherapy for palliation of gastroesophageal cancer. Sixty-five patients presenting with gastroesophageal carcinoma to the Royal Infirmary, Glasgow between January 1999 and December 2005 and who received palliative chemotherapy or chemo-radiotherapy were studied. ECOG-ps, C-reactive protein, and albumin were recorded at diagnosis. Patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS of 1 and patients with a normal C-reactive protein and albumin were allocated a score of 0. Toxicity was recorded using the Common Toxicity Criteria. The minimum follow up was 14 months. During the follow-up period, 59 (91%) of the patients died. On univariate and multivariate survival analysis, only the GPS (hazard ratios 1.65, 95% CI 1.10-2.47, P < 0.05) was a significant independent predictor of cancer survival. In addition, in comparison with patients with GPS of 0, those patients with a GPS of 1 or 2 required more frequent chemotherapy dose reduction (P < 0.05), were less likely to exhibit a clinical response to treatment (P < 0.05), and had shorter survival (P < 0.05). The presence of a systemic inflammatory response, as evidenced by the GPS, appears to be superior to the subjective assessment of performance status (ECOG-ps) in predicting the response to platinum-based chemotherapy in patients with advanced gastroesophageal cancer.

Propensity Score Estimation With Boosted Regression for Evaluating Causal Effects in Observational Studies

ERIC Educational Resources Information Center

McCaffrey, Daniel F.; Ridgeway, Greg; Morral, Andrew R.

2004-01-01

Causal effect modeling with naturalistic rather than experimental data is challenging. In observational studies participants in different treatment conditions may also differ on pretreatment characteristics that influence outcomes. Propensity score methods can theoretically eliminate these confounds for all observed covariates, but accurate…

Increased correlation coefficient between the written test score and tutors' performance test scores after training of tutors for assessment of medical students during problem-based learning course in Malaysia.

PubMed

Jaiprakash, Heethal; Min, Aung Ko Ko; Ghosh, Sarmishtha

2016-03-01

This paper is aimed at finding if there was a change of correlation between the written test score and tutors' performance test scores in the assessment of medical students during a problem-based learning (PBL) course in Malaysia. This is a cross-sectional observational study, conducted among 264 medical students in two groups from November 2010 to November 2012. The first group's tutors did not receive tutor training; while the second group's tutors were trained in the PBL process. Each group was divided into high, middle and low achievers based on their end-of-semester exam scores. PBL scores were taken which included written test scores and tutors' performance test scores. Pearson correlation coefficient was calculated between the two kinds of scores in each group. The correlation coefficient between the written scores and tutors' scores in group 1 was 0.099 (p<0.001) and for group 2 was 0.305 (p<0.001). The higher correlation coefficient in the group where tutors received the PBL training reinforces the importance of tutor training before their participation in the PBL course.

Scoring haemophilic arthropathy on X-rays: improving inter- and intra-observer reliability and agreement using a consensus atlas.

PubMed

Foppen, Wouter; van der Schaaf, Irene C; Beek, Frederik J A; Verkooijen, Helena M; Fischer, Kathelijn

2016-06-01

The radiological Pettersson score (PS) is widely applied for classification of arthropathy to evaluate costly haemophilia treatment. This study aims to assess and improve inter- and intra-observer reliability and agreement of the PS. Two series of X-rays (bilateral elbows, knees, and ankles) of 10 haemophilia patients (120 joints) with haemophilic arthropathy were scored by three observers according to the PS (maximum score 13/joint). Subsequently, (dis-)agreement in scoring was discussed until consensus. Example images were collected in an atlas. Thereafter, second series of 120 joints were scored using the atlas. One observer rescored the second series after three months. Reliability was assessed by intraclass correlation coefficients (ICC), agreement by limits of agreement (LoA). Median Pettersson score at joint level (PSjoint) of affected joints was 6 (interquartile range 3-9). Using the consensus atlas, inter-observer reliability of the PSjoint improved significantly from 0.94 (95 % confidence interval (CI) 0.91-0.96) to 0.97 (CI 0.96-0.98). LoA improved from ±1.7 to ±1.1 for the PSjoint. Therefore, true differences in arthropathy were differences in the PSjoint of >2 points. Intra-observer reliability of the PSjoint was 0.98 (CI 0.97-0.98), intra-observer LoA were ±0.9 points. Reliability and agreement of the PS improved by using a consensus atlas. • Reliability of the Pettersson score significantly improved using the consensus atlas. • The presented consensus atlas improved the agreement among observers. • The consensus atlas could be recommended to obtain a reproducible Pettersson score.

Enhancement of toxicity of saporin-based toxins by Gypsophila saponins--kinetic of the saponin.

PubMed

Weng, Alexander; Görick, Cornelia; Melzig, Matthias F

2009-08-01

Saponins are amphiphilic substances consisting of a hydrophobic backbone with one or two hydrophilic sugar units. Recently it was shown that saponinum album (SA) from Gypsophila paniculata L. enhanced cytotoxicity of a saporin-based chimeric toxin (up to 385,000-fold) as well as the toxicity of saporin (up to 100,000-fold) with N-glycosidase activity. Previously we have shown that toxicity of other N-glycosidases such as ricin A-chain, nigrin b, and toxins such as diphtheria toxin or microcystin-LR was not enhanced by SA. This points to a specific SA-dependent mechanism of toxicity enhancement on saporin and saporin-based toxins. Although the cytotoxicity enhancing effect was observed in up to 10 different cell lines, nothing is known about the kinetic of SA under cell culture conditions. Therefore SA was titrated, and the uptake respective liberation profile of SA was investigated in ECV-304 cells. Treatment of cells with [(3)H]-SA leads to an immediate uptake of saponin molecules. After cells were saturated with [(3)H]-SA, a first equilibrium (first eq.) was reached. The first eq. was disturbed by washing until a second equilibrium was reached between the activity observed within cells and that seen in the supernatant. After a further extensive washing, a small portion of saponin molecules remained durable associated with the cell. This portion was sufficient to induce a drastic toxicity enhancement on saporin indicating a long-lasting sensitization of cells against the toxin.

The autism diagnostic observation schedule, module 4: revised algorithm and standardized severity scores.

PubMed

Hus, Vanessa; Lord, Catherine

2014-08-01

The recently published Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) includes revised diagnostic algorithms and standardized severity scores for modules used to assess younger children. A revised algorithm and severity scores are not yet available for Module 4, used with verbally fluent adults. The current study revises the Module 4 algorithm and calibrates raw overall and domain totals to provide metrics of autism spectrum disorder (ASD) symptom severity. Sensitivity and specificity of the revised Module 4 algorithm exceeded 80 % in the overall sample. Module 4 calibrated severity scores provide quantitative estimates of ASD symptom severity that are relatively independent of participant characteristics. These efforts increase comparability of ADOS scores across modules and should facilitate efforts to examine symptom trajectories from toddler to adulthood.

Five Methods to Score the Teacher Observation of Classroom Adaptation Checklist and to Examine Group Differences

ERIC Educational Resources Information Center

Wang, Ze; Rohrer, David; Chuang, Chi-ching; Fujiki, Mayo; Herman, Keith; Reinke, Wendy

2015-01-01

This study compared 5 scoring methods in terms of their statistical assumptions. They were then used to score the Teacher Observation of Classroom Adaptation Checklist, a measure consisting of 3 subscales and 21 Likert-type items. The 5 methods used were (a) sum/average scores of items, (b) latent factor scores with continuous indicators, (c)…

Enhancing the Value of Population-Based Risk Scores for Institutional-Level Use.

PubMed

Raza, Sajjad; Sabik, Joseph F; Rajeswaran, Jeevanantham; Idrees, Jay J; Trezzi, Matteo; Riaz, Haris; Javadikasgari, Hoda; Nowicki, Edward R; Svensson, Lars G; Blackstone, Eugene H

2016-07-01

We hypothesized that factors associated with an institution's residual risk unaccounted for by population-based models may be identifiable and used to enhance the value of population-based risk scores for quality improvement. From January 2000 to January 2010, 4,971 patients underwent aortic valve replacement (AVR), either isolated (n = 2,660) or with concomitant coronary artery bypass grafting (AVR+CABG; n = 2,311). Operative mortality and major morbidity and mortality predicted by The Society of Thoracic Surgeons (STS) risk models were compared with observed values. After adjusting for patients' STS score, additional and refined risk factors were sought to explain residual risk. Differences between STS model coefficients (risk-factor strength) and those specific to our institution were calculated. Observed operative mortality was less than predicted for AVR (1.6% [42 of 2,660] vs 2.8%, p < 0.0001) and AVR+CABG (2.6% [59 of 2,311] vs 4.9%, p < 0.0001). Observed major morbidity and mortality was also lower than predicted for isolated AVR (14.6% [389 of 2,660] vs 17.5%, p < 0.0001) and AVR+CABG (20.0% [462 of 2,311] vs 25.8%, p < 0.0001). Shorter height, higher bilirubin, and lower albumin were identified as additional institution-specific risk factors, and body surface area, creatinine, glomerular filtration rate, blood urea nitrogen, and heart failure across all levels of functional class were identified as refined risk-factor variables associated with residual risk. In many instances, risk-factor strength differed substantially from that of STS models. Scores derived from population-based models can be enhanced for institutional level use by adjusting for institution-specific additional and refined risk factors. Identifying these and measuring differences in institution-specific versus population-based risk-factor strength can identify areas to target for quality improvement initiatives. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier

Validation of the German Diabetes Risk Score within a population-based representative cohort.

PubMed

Hartwig, S; Kuss, O; Tiller, D; Greiser, K H; Schulze, M B; Dierkes, J; Werdan, K; Haerting, J; Kluttig, A

2013-09-01

To validate the German Diabetes Risk Score within the population-based cohort of the Cardiovascular Disease - Living and Ageing in Halle (CARLA) study. The sample included 582 women and 719 men, aged 45-83 years, who did not have diabetes at baseline. The individual risk of every participant was calculated using the German Diabetes Risk Score, which was modified for 4 years of follow-up. Predicted probabilities and observed outcomes were compared using Hosmer-Lemeshow goodness-of-fit tests and receiver-operator characteristic analyses. Changes in prediction power were investigated by expanding the German Diabetes Risk Score to include metabolic variables and by subgroup analyses. We found 58 cases of incident diabetes. The median 4-year probability of developing diabetes based on the German Diabetes Risk Score was 6.5%. The observed and predicted probabilities of developing diabetes were similar, although estimation was imprecise owing to the small number of cases, and the Hosmer-Lemeshow test returned a poor correlation (chi-squared = 55.3; P = 5.8*10⁻¹²). The area under the receiver-operator characteristic curve (AUC) was 0.70 (95% CI 0.64-0.77), and after excluding participants ≥66 years old, the AUC increased to 0.77 (95% CI 0.70-0.84). Consideration of glycaemic diagnostic variables, in addition to self-reported diabetes, reduced the AUC to 0.65 (95% CI 0.58-0.71). A new model that included the German Diabetes Risk Score and blood glucose concentration (AUC 0.81; 95% CI 0.76-0.86) or HbA(1c) concentration (AUC 0.84; 95% CI 0.80-0.91) was found to peform better. Application of the German Diabetes Risk Score in the CARLA cohort did not reproduce the findings in the European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam study, which may be explained by cohort differences and model overfit in the latter; however, a high score does provide an indication of increased risk of diabetes. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes

Prioritization of reproductive toxicants in unconventional oil and gas operations using a multi-country regulatory data-driven hazard assessment.

PubMed

Inayat-Hussain, Salmaan H; Fukumura, Masao; Muiz Aziz, A; Jin, Chai Meng; Jin, Low Wei; Garcia-Milian, Rolando; Vasiliou, Vasilis; Deziel, Nicole C

2018-08-01

Recent trends have witnessed the global growth of unconventional oil and gas (UOG) production. Epidemiologic studies have suggested associations between proximity to UOG operations with increased adverse birth outcomes and cancer, though specific potential etiologic agents have not yet been identified. To perform effective risk assessment of chemicals used in UOG production, the first step of hazard identification followed by prioritization specifically for reproductive toxicity, carcinogenicity and mutagenicity is crucial in an evidence-based risk assessment approach. To date, there is no single hazard classification list based on the United Nations Globally Harmonized System (GHS), with countries applying the GHS standards to generate their own chemical hazard classification lists. A current challenge for chemical prioritization, particularly for a multi-national industry, is inconsistent hazard classification which may result in misjudgment of the potential public health risks. We present a novel approach for hazard identification followed by prioritization of reproductive toxicants found in UOG operations using publicly available regulatory databases. GHS classification for reproductive toxicity of 157 UOG-related chemicals identified as potential reproductive or developmental toxicants in a previous publication was assessed using eleven governmental regulatory agency databases. If there was discordance in classifications across agencies, the most stringent classification was assigned. Chemicals in the category of known or presumed human reproductive toxicants were further evaluated for carcinogenicity and germ cell mutagenicity based on government classifications. A scoring system was utilized to assign numerical values for reproductive health, cancer and germ cell mutation hazard endpoints. Using a Cytoscape analysis, both qualitative and quantitative results were presented visually to readily identify high priority UOG chemicals with evidence of multiple

Pharmacophore-Based Similarity Scoring for DOCK

PubMed Central

2015-01-01

Pharmacophore modeling incorporates geometric and chemical features of known inhibitors and/or targeted binding sites to rationally identify and design new drug leads. In this study, we have encoded a three-dimensional pharmacophore matching similarity (FMS) scoring function into the structure-based design program DOCK. Validation and characterization of the method are presented through pose reproduction, crossdocking, and enrichment studies. When used alone, FMS scoring dramatically improves pose reproduction success to 93.5% (∼20% increase) and reduces sampling failures to 3.7% (∼6% drop) compared to the standard energy score (SGE) across 1043 protein–ligand complexes. The combined FMS+SGE function further improves success to 98.3%. Crossdocking experiments using FMS and FMS+SGE scoring, for six diverse protein families, similarly showed improvements in success, provided proper pharmacophore references are employed. For enrichment, incorporating pharmacophores during sampling and scoring, in most cases, also yield improved outcomes when docking and rank-ordering libraries of known actives and decoys to 15 systems. Retrospective analyses of virtual screenings to three clinical drug targets (EGFR, IGF-1R, and HIVgp41) using X-ray structures of known inhibitors as pharmacophore references are also reported, including a customized FMS scoring protocol to bias on selected regions in the reference. Overall, the results and fundamental insights gained from this study should benefit the docking community in general, particularly researchers using the new FMS method to guide computational drug discovery with DOCK. PMID:25229837

Validation of a literature-based adherence score to Mediterranean diet: the MEDI-LITE score.

PubMed

Sofi, Francesco; Dinu, Monica; Pagliai, Giuditta; Marcucci, Rossella; Casini, Alessandro

2017-09-01

Numerous studies have demonstrated a relationship between adherence to Mediterranean diet and prevention of chronic degenerative diseases. The aim of this study was to validate a novel instrument to measure adherence to Mediterranean diet based on the literature (the MEDI-LITE score). Two-hundred-and-four clinically healthy subjects completed both the MEDI-LITE score and the validated MedDietScore (MDS). Significant positive correlation between the MEDI-LITE and the MDS scores was found in the study population (R = .70; p < .0001). Furthermore, statistically significant positive correlations were found for all the nine different food groups. According to the receiver operating characteristic (ROC) curve analysis, MEDI-LITE evidenced a significant discriminative capacity between adherents and non-adherents to the Mediterranean diet pattern (optimal cut-off point = 8.50; sensitivity = 96%; specificity = 38%). In conclusion, our findings show that the MEDI-LITE score well correlate with MDS in both global score and in most of the items related to the specific food categories.

Wearable PPG sensor based alertness scoring system.

PubMed

Dey, Jishnu; Bhowmik, Tanmoy; Sahoo, Saswata; Tiwari, Vijay Narayan

2017-07-01

Quantifying mental alertness in today's world is important as it enables the person to adopt lifestyle changes for better work efficiency. Miniaturized sensors in wearable devices have facilitated detection/monitoring of mental alertness. Photoplethysmography (PPG) sensors through Heart Rate Variability (HRV) offer one such opportunity by providing information about one's daily alertness levels without requiring any manual interference from the user. In this paper, a smartwatch based alertness estimation system is proposed. Data collected from PPG sensor of smartwatch is processed and fed to machine learning based model to get a continuous alertness score. Utility functions are designed based on statistical analysis to give a quality score on different stages of alertness such as awake, long sleep and short duration power nap. An intelligent data collection approach is proposed in collaboration with the motion sensor in the smartwatch to reduce battery drainage. Overall, our proposed wearable based system provides a detailed analysis of alertness over a period in a systematic and optimized manner. We were able to achieve an accuracy of 80.1% for sleep/awake classification along with alertness score. This opens up the possibility for quantifying alertness levels using a single PPG sensor for better management of health related activities including sleep.

Dose-finding designs using a novel quasi-continuous endpoint for multiple toxicities

PubMed Central

Ezzalfani, Monia; Zohar, Sarah; Qin, Rui; Mandrekar, Sumithra J; Deley, Marie-Cécile Le

2013-01-01

The aim of a phase I oncology trial is to identify a dose with an acceptable safety profile. Most phase I designs use the dose-limiting toxicity, a binary endpoint, to assess the unacceptable level of toxicity. The dose-limiting toxicity might be incomplete for investigating molecularly targeted therapies as much useful toxicity information is discarded. In this work, we propose a quasi-continuous toxicity score, the total toxicity profile (TTP), to measure quantitatively and comprehensively the overall severity of multiple toxicities. We define the TTP as the Euclidean norm of the weights of toxicities experienced by a patient, where the weights reflect the relative clinical importance of each grade and toxicity type. We propose a dose-finding design, the quasi-likelihood continual reassessment method (CRM), incorporating the TTP score into the CRM, with a logistic model for the dose–toxicity relationship in a frequentist framework. Using simulations, we compared our design with three existing designs for quasi-continuous toxicity score (the Bayesian quasi-CRM with an empiric model and two nonparametric designs), all using the TTP score, under eight different scenarios. All designs using the TTP score to identify the recommended dose had good performance characteristics for most scenarios, with good overdosing control. For a sample size of 36, the percentage of correct selection for the quasi-likelihood CRM ranged from 80% to 90%, with similar results for the quasi-CRM design. These designs with TTP score present an appealing alternative to the conventional dose-finding designs, especially in the context of molecularly targeted agents. PMID:23335156

The SED-TOX: Toxicity-directed management tool to assess and rank sediments based on their hazard -- concept and application

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

Bombardier, M.; Bermingham, N.

1999-04-01

This article introduces the sediment Toxicity (SED-TOX) Index for the assessment and ranking of toxic hazards in sediment. Major features include expression of toxicity responses on a single scale of measurement (dry weight-based toxic units), consideration of multiple routes of exposure (pore water, organic extract, wet sediment, and whole sediment), application of differential treatments to toxicity data depending on the level of response, and use of weighting factors to discriminate sediment exposure phases and effect endpoints on the basis of sensitivity. A battery of seven bioassays with four test species (Vibrio fischeri, Escherichia coli, Lytechinus pictus, and Amphiporeia virginiana) wasmore » conducted on 49 marine sediment samples collected from six sites at Anse-a-Beaufils and Cap-aux-Meules, which are in the Gulf of St. Lawrence. The SED-TOX scores were calculated for each sampling station and compared with sediment contaminant concentrations. Results indicate that physico-chemical characterization is not sufficient to assess contaminated-sediment hazard for organisms; furthermore, using several exposure phases and test species belonging to various trophic levels increases the possibility of correctly identifying toxic sediments. The results of this study indicate that the SED-TOX approach is valuable as a toxicity assessment and ranking tool for sediments. It could easily be combined with other measures of ecosystem disturbance to discriminate between polluted and unpolluted sites.« less

A dysmorphology score system for assessing embryo abnormalities in rat whole embryo culture.

PubMed

Zhang, Cindy X; Danberry, Tracy; Jacobs, Mary Ann; Augustine-Rauch, Karen

2010-12-01

The rodent whole embryo culture (WEC) system is a well-established model for characterizing developmental toxicity of test compounds and conducting mechanistic studies. Laboratories have taken various approaches in describing type and severity of developmental findings of organogenesis-stage rodent embryos, but the Brown and Fabro morphological score system is commonly used as a quantitative approach. The associated score criteria is based upon developmental stage and growth parameters, where a series of embryonic structures are assessed and assigned respective scores relative to their gestational stage, with a Total Morphological Score (TMS) assigned to the embryo. This score system is beneficial because it assesses a series of stage-specific anatomical landmarks, facilitating harmonized evaluation across laboratories. Although the TMS provides a quantitative approach to assess growth and determine developmental delay, it is limited to its ability to identify and/or delineate subtle or structure-specific abnormalities. Because of this, the TMS may not be sufficiently sensitive for identifying compounds that induce structure or organ-selective effects. This study describes a distinct morphological score system called the "Dysmorphology Score System (DMS system)" that has been developed for assessing gestation day 11 (approximately 20-26 somite stage) rat embryos using numerical scores to differentiate normal from abnormal morphology and define the respective severity of dysmorphology of specific embryonic structures and organ systems. This method can also be used in scoring mouse embryos of the equivalent developmental stage. The DMS system enhances capabilities to rank-order compounds based upon teratogenic potency, conduct structure- relationships of chemicals, and develop statistical prediction models to support abbreviated developmental toxicity screens. © 2010 Wiley-Liss, Inc.

A Novel Scoring Metrics for Quality Assurance of Ocean Color Observations

NASA Astrophysics Data System (ADS)

Wei, J.; Lee, Z.

2016-02-01

Interpretation of the ocean bio-optical properties from ocean color observations depends on the quality of the ocean color data, specifically the spectrum of remote sensing reflectance (Rrs). The in situ and remotely measured Rrs spectra are inevitably subject to errors induced by instrument calibration, sea-surface correction and atmospheric correction, and other environmental factors. Great efforts have been devoted to the ocean color calibration and validation. Yet, there exist no objective and consensus criteria for assessment of the ocean color data quality. In this study, the gap is filled by developing a novel metrics for such data quality assurance and quality control (QA/QC). This new QA metrics is not intended to discard "suspicious" Rrs spectra from available datasets. Rather, it takes into account the Rrs spectral shapes and amplitudes as a whole and grades each Rrs spectrum. This scoring system is developed based on a large ensemble of in situ hyperspectral remote sensing reflectance data measured from various aquatic environments and processed with robust procedures. This system is further tested with the NASA bio-Optical Marine Algorithm Data set (NOMAD), with results indicating significant improvements in the estimation of bio-optical properties when Rrs spectra marked with higher quality assurance are used. This scoring system is further verified with simulated data and satellite ocean color data in various regions, and we envision higher quality ocean color products with the implementation of such a quality screening system.

Toxicity Assessment of the Xanthid Crab Demania cultripes from Cebu Island, Philippines

PubMed Central

Asakawa, Manabu; Gomez-Delan, Gloria; Tsuruda, Shintaro; Shimomura, Michitaka; Shida, Yasuo; Taniyama, Shigeto; Barte-Quilantang, Mercy; Shindo, Jo

2010-01-01

Several cases of poisoning resulting in human fatalities and stemming from the ingestion of coral reef crabs have been reported from the Indo-Pacific region. We assessed the toxicity of the unidentified xanthid crab collected from the Camotes Sea off the eastern coast of Cebu Island, central Visayas region of Philippines from the food hygienic point of view. All seven specimens, which were identified with Demania cultripes, collected in 2006 were toxic to mice irrespective of the season of collection and induced paralytic symptoms typical of tetrodotoxin (TTX) and paralytic shellfish poison (PSP). The activity was expressed in mouse unit (MU) being defined as the amount of TTX to kill a 20 g ddY male mice in 30 min after i.p. injection. Toxicity scores for viscera and appendages of specimens were 18.2 ± 16.0 (mean ± S.D.) and 4.4 ± 2.6 MU/g, respectively. The highest individual toxicity scores observed for viscera and appendages were 52.1 and 7.7 MU/g, respectively. The frequency of toxic samples was 100%. Toxin profiles as determined by high-performance liquid chromatography-fluorescent detection analysis (HPLC-FLD) revealed that TTX was the main toxic principle accounting for about 90% of the total toxicity along with 4-epi TTX and 4,9-anhydroTTX. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis revealed mass fragment ion peaks at m/z 376, 392 and 407, which were characteristic of the quinazoline skeleton (C9-base) specific to TTX. In addition, only a small amount of PSP containing gonyautoxins1–4 and hydroxysaxitoxin was detected. To our knowledge, this is the first report presenting evidence of occurrence of TTX and PSP in the xanthid crab D. cultripes inhabiting waters surrounding Cebu Island. From food hygienic point of view, people in coastal areas should be warned of the potential hazard of this crab in order to prevent its intentional or accidental consumption. PMID:21209702

Sarcopenia is linked to treatment toxicity in patients with metastatic colorectal cancer.

PubMed

Barret, Maximilien; Antoun, Sami; Dalban, Cécile; Malka, David; Mansourbakht, Touraj; Zaanan, Aziz; Latko, Ewa; Taieb, Julien

2014-01-01

Chemotherapy toxicity could be linked to decreased skeletal muscle (sarcopenia). We evaluated the effect of sarcopenia on chemotherapy toxicity among metastatic colorectal cancer (mCRC) patients. All consecutive mCRC patients in 3 hospitals were enrolled in this prospective, cross-sectional, multicenter study. Several nutritional indexes and scores were generated. Computed tomography (CT) images were analyzed to evaluate cross-sectional areas of muscle tissue (MT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Toxicities were evaluated in the 2 mo following clinical evaluation. Fifty-one mCRC patients were included in the study. Sarcopenia was observed in 71% of patients (39% of women and 82% of men) whereas only 4% and 18% were considered as underweight using body mass index (BMI) or severely malnourished using the Nutritional Risk Index (NRI), respectively. Grade 3-4 toxicities were observed in 28% of patients. In multivariate analysis including age, sex, BMI, sarcopenia, SAT, and VAT, the only factor associated with Grade 3-4 toxicities was sarcopenia (odds ratio = 13.55; 95% confidence interval [1.08; 169.31], P = 0.043). In mCRC patients undergoing chemotherapy, sarcopenia was much more frequently observed than visible malnutrition. Despite the small number of patients included in our study, we found sarcopenia to be significantly associated with severe chemotherapy toxicity.

Investigation on modes of toxic action to rats based on aliphatic and aromatic compounds and comparison with fish toxicity based on exposure routes.

PubMed

He, Jia; Li, Jin J; Wen, Yang; Tai, Hong W; Yu, Yang; Qin, Wei C; Su, Li M; Zhao, Yuan H

2015-06-01

The modes of toxic action (MOAs) play an important role in the assessment of the ecotoxicity of organic pollutants. However, few studies have been reported on the MOAs in rat toxicity. In this paper, the toxic contributions of functional groups in 1255 aromatic compounds were calculated from regression and were then compared with the toxic contributions in aliphatic compounds. The results show that some functional groups have same toxic contributions both in aromatic and aliphatic compounds, but some have not. To investigate the MOAs in rat toxicity, the distribution of toxic ratio (TR) was examined for well-known baseline and less inert compounds and thresholds of log TR=0.3 and 0.5 were used to classify baseline, less inert and reactive compounds. The results showed that some compounds identified as baseline compounds in fish toxicity were also classified as baseline compounds in rat toxicity. Except for phenols and anilines which were identified as less inert compounds in fish toxicity, aromatic compounds with functional groups such as ether, nitrile, nitrophenol, isocyanatoe and chloro were identified as less inert chemicals in rat toxicity. Reactive compounds identified in fish toxicity exhibit greater toxicity to rats. These compounds can undergo nucleophilic substitution, acylation and Schiff base formation with biological macromolecules. The critical body residues (CBRs) calculated from absorption and bioconcentration show that log 1/CBRs in rat toxicity are not equal to that in fish for some compounds. It suggests that the exposure route can affect the identification of MOAs between these two species for these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

Correlation of emphysema score with perceived malignancy of pulmonary nodules: a multi-observer study using the LIDC-IDRI CT lung database

NASA Astrophysics Data System (ADS)

Wiemker, Rafael; Bülow, Thomas; Blaffert, Thomas; Dharaiya, Ekta

2009-02-01

Presence of emphysema is recognized to be one of the single most significant risk factors in risk models for the prediction of lung cancer. Therefore, an automatically computed emphysema score would be a prime candidate as an additional numerical feature for computer aided diagnosis (CADx) for indeterminate pulmonary nodules. We have applied several histogram-based emphysema scores to 460 thoracic CT scans from the IDRI CT lung image database, and analyzed the emphysema scores in conjunction with 3000 nodule malignancy ratings of 1232 pulmonary nodules made by expert observers. Despite the emphysema being a known risk factor, we have not found any impact on the readers' malignancy rating of nodules found in a patient with higher emphysema score. We have also not found any correlation between the number of expert-detected nodules in a patient and his emphysema score, or the relative craniocaudal location of the nodules and their malignancy rating. The inter-observer agreement of the expert ratings was excellent on nodule diameter (as derived from manual delineations), good for calcification, and only modest for malignancy and shape descriptions such as spiculation, lobulation, margin, etc.

Integrated scientific data bases review on asulacrine and associated toxicity.

PubMed

Afzal, Attia; Sarfraz, Muhammad; Wu, Zimei; Wang, Guangji; Sun, Jianguo

2016-08-01

Asulacrine (ASL), a weakly basic and highly lipophilic drug was synthesized in 1980's in cancer research laboratory of Auckland by modifications to the acridine portion of amsacrine on 3-, 4- and 5-substitution patterns. In contrast to its precursor amsacrine (m-AMSA), ASL was effective not only against leukemia and Lewis lung tumor system but also a wide variety of solid tumor. Its metabolic pathway is not same to amsacrine hence different side effects, hepatotoxicity and excretion was observed. Asulacrine is under phase II clinical trials and has showed promising results but its toxicity especially phlebitis is stumbling block in its clinical implementation. This review is an effort to give a possible clue, based on scientifically proven results, to the researchers to solve the mystery of associated toxicity, phlebitis. Review covers the available literature on asulacrine and other acridine derivatives regarding pharmacology, pharmacokinetics, quantitative structure activity relationship and toxicology via electronic search using scientific databases like PubMed and others. To date, all abstracts and full-text articles were discussed and analyzed. The tabulated comparisons and circuitry mechanism of ASL are the added features of the review which give a complete understanding of hidden aspects of possible route cause of associated toxicity, the phlebitis. Copyright © 2016. Published by Elsevier Ireland Ltd.

Cheminformatics meets molecular mechanics: a combined application of knowledge-based pose scoring and physical force field-based hit scoring functions improves the accuracy of structure-based virtual screening.

PubMed

Hsieh, Jui-Hua; Yin, Shuangye; Wang, Xiang S; Liu, Shubin; Dokholyan, Nikolay V; Tropsha, Alexander

2012-01-23

Poor performance of scoring functions is a well-known bottleneck in structure-based virtual screening (VS), which is most frequently manifested in the scoring functions' inability to discriminate between true ligands vs known nonbinders (therefore designated as binding decoys). This deficiency leads to a large number of false positive hits resulting from VS. We have hypothesized that filtering out or penalizing docking poses recognized as non-native (i.e., pose decoys) should improve the performance of VS in terms of improved identification of true binders. Using several concepts from the field of cheminformatics, we have developed a novel approach to identifying pose decoys from an ensemble of poses generated by computational docking procedures. We demonstrate that the use of target-specific pose (scoring) filter in combination with a physical force field-based scoring function (MedusaScore) leads to significant improvement of hit rates in VS studies for 12 of the 13 benchmark sets from the clustered version of the Database of Useful Decoys (DUD). This new hybrid scoring function outperforms several conventional structure-based scoring functions, including XSCORE::HMSCORE, ChemScore, PLP, and Chemgauss3, in 6 out of 13 data sets at early stage of VS (up 1% decoys of the screening database). We compare our hybrid method with several novel VS methods that were recently reported to have good performances on the same DUD data sets. We find that the retrieved ligands using our method are chemically more diverse in comparison with two ligand-based methods (FieldScreen and FLAP::LBX). We also compare our method with FLAP::RBLB, a high-performance VS method that also utilizes both the receptor and the cognate ligand structures. Interestingly, we find that the top ligands retrieved using our method are highly complementary to those retrieved using FLAP::RBLB, hinting effective directions for best VS applications. We suggest that this integrative VS approach combining

An internally validated new clinical and inflammation-based prognostic score for patients with advanced hepatocellular carcinoma treated with sorafenib.

PubMed

Diaz-Beveridge, R; Bruixola, G; Lorente, D; Caballero, J; Rodrigo, E; Segura, Á; Akhoundova, D; Giménez, A; Aparicio, J

2018-03-01

Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis. To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management. Retrospective review of 145 pts bNLR, overall toxicity, early toxicity rates and overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the coefficients found in the Cox analysis. ROC curves and pseudoR2 index were used for internal validation. Discrimination ability and calibration were tested by Harrel's c-index (HCI) and Akaike criteria (AIC). The optimal bNLR cut-off for the prediction of OS was 4 (AUC 0.62). Independent prognostic factors in multivariate analysis for OS were performance status (PS) (p < .0001), Child-Pugh (C-P) score (p = 0.005), early-onset diarrhoea (p = 0.006) and BNLR (0.011). The prognostic score based on these four variables was found efficient (HCI = 0.659; AIC = 1.180). Four risk groups for OS could be identified: a very low-risk (median OS = 48.6 months), a low-risk (median OS = 11.6 months), an intermediate-risk (median OS = 8.3 months) and a high-risk group (median OS = 4.4 months). PS and C-P score were the main prognostic factors for OS, followed by early-onset diarrhoea and bNLR. We identified four risk groups for OS depending on these parameters. This prognostic model could be useful for patient stratification, but an external validation is needed.

Observational studies using propensity score analysis underestimated the effect sizes in critical care medicine.

PubMed

Zhang, Zhongheng; Ni, Hongying; Xu, Xiao

2014-08-01

Propensity score (PS) analysis has been increasingly used in critical care medicine; however, its validation has not been systematically investigated. The present study aimed to compare effect sizes in PS-based observational studies vs. randomized controlled trials (RCTs) (or meta-analysis of RCTs). Critical care observational studies using PS were systematically searched in PubMed from inception to April 2013. Identified PS-based studies were matched to one or more RCTs in terms of population, intervention, comparison, and outcome. The effect sizes of experimental treatments were compared for PS-based studies vs. RCTs (or meta-analysis of RCTs) with sign test. Furthermore, ratio of odds ratio (ROR) was calculated from the interaction term of treatment × study type in a logistic regression model. A ROR < 1 indicates greater benefit for experimental treatment in RCTs compared with PS-based studies. RORs of each comparison were pooled by using meta-analytic approach with random-effects model. A total of 20 PS-based studies were identified and matched to RCTs. Twelve of the 20 comparisons showed greater beneficial effect for experimental treatment in RCTs than that in PS-based studies (sign test P = 0.503). The difference was statistically significant in four comparisons. ROR can be calculated from 13 comparisons, of which four showed significantly greater beneficial effect for experimental treatment in RCTs. The pooled ROR was 0.71 (95% CI: 0.63, 0.79; P = 0.002), suggesting that RCTs (or meta-analysis of RCTs) were more likely to report beneficial effect for the experimental treatment than PS-based studies. The result remained unchanged in sensitivity analysis and meta-regression. In critical care literature, PS-based observational study is likely to report less beneficial effect of experimental treatment compared with RCTs (or meta-analysis of RCTs). Copyright © 2014 Elsevier Inc. All rights reserved.

Diet composition exacerbates or attenuates soman toxicity in rats: implied metabolic control of nerve agent toxicity.

PubMed

Myers, Todd M; Langston, Jeffrey L

2011-06-01

To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was recorded throughout the study. Toxic signs and survival were evaluated at key times for up to 72 h following soman exposure. Additionally, acquisition of discriminated shuttlebox avoidance performance was characterized beginning 24h after soman challenge and across the next 8 d (six behavioral sessions). Prior to exposure, body weight was highest in the standard diet group and lowest in the ketogenic diet group. Upon exposure, differences in soman toxicity as a function of diet became apparent within the first hour, with mortality in the glucose-enriched diet group reaching 80% and exceeding all other groups (in which mortality ranged from 0 to 6%). At 72 h after exposure, mortality was 100% in the glucose-enriched diet group, and survival approximated 50% in the standard and choline-enriched diet groups, but equaled 87% in the ketogenic diet group. Body weight loss was significantly reduced in the ketogenic and choline-enriched diet groups, relative to the standard diet group. At 1 and 4h after exposure, rats in the ketogenic diet group had significantly lower toxic sign scores than all other groups. The ketogenic diet group performed significantly better than the standard diet group on two measures of active avoidance performance. The exacerbated soman toxicity observed in the glucose-enriched diet group coupled with the attenuated soman toxicity observed in the ketogenic diet group implicates glucose availability in the toxic effects of soman. This increased glucose availability may enhance acetylcholine synthesis and/or utilization, thereby exacerbating peripheral and central soman toxicity. Published by Elsevier B.V.

¹H NMR-based metabolic profiling of naproxen-induced toxicity in rats.

PubMed

Jung, Jeeyoun; Park, Minhwa; Park, Hye Jin; Shim, Sun Bo; Cho, Yang Ha; Kim, Jinho; Lee, Ho-Sub; Ryu, Do Hyun; Choi, Donwoong; Hwang, Geum-Sook

2011-01-15

The dose-dependent perturbations in urinary metabolite concentrations caused by naproxen toxicity were investigated using ¹H NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic evaluation of naproxen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) of ¹H NMR from rat urine revealed a dose-dependent metabolic shift between the vehicle-treated control rats and rats treated with low-dose (10 mg/kg body weight), moderate-dose (50 mg/kg), and high-dose (100 mg/kg) naproxen, coinciding with their gastric damage scores after naproxen administration. The resultant metabolic profiles demonstrate that the naproxen-induced gastric damage exhibited energy metabolism perturbations that elevated their urinary levels of citrate, cis-aconitate, creatine, and creatine phosphate. In addition, naproxen administration decreased choline level and increased betaine level, indicating that it depleted the main protective constituent of the gastric mucosa. Moreover, naproxen stimulated the decomposition of tryptophan into kynurenate, which inhibits fibroblast growth factor-1 and delays ulcer healing. These findings demonstrate that ¹H NMR-based urinary metabolic profiling can facilitate noninvasive and rapid diagnosis of drug side effects and is suitable for elucidating possible biological pathways perturbed by drug toxicity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The Autism Diagnostic Observation Schedule, Module 4: Revised Algorithm and Standardized Severity Scores

PubMed Central

Hus, Vanessa; Lord, Catherine

2014-01-01

The Autism Diagnostic Observation Schedule, 2nd Edition includes revised diagnostic algorithms and standardized severity scores for modules used to assess children and adolescents of varying language abilities. Comparable revisions have not yet been applied to the Module 4, used with verbally fluent adults. The current study revises the Module 4 algorithm and calibrates raw overall and domain totals to provide metrics of ASD symptom severity. Sensitivity and specificity of the revised Module 4 algorithm exceeded 80% in the overall sample. Module 4 calibrated severity scores provide quantitative estimates of ASD symptom severity that are relatively independent of participant characteristics. These efforts increase comparability of ADOS scores across modules and should facilitate efforts to increase understanding of adults with ASD. PMID:24590409

SSRIs and risk of suicide attempts in young people - A Danish observational register-based historical cohort study, using propensity score.

PubMed

Christiansen, Erik; Agerbo, Esben; Bilenberg, Niels; Stenager, Elsebeth

2016-01-01

SSRIs are widely used in the treatment of mental illness for both children and adults. Studies have found a slightly increased risk of suicidal thoughts and suicide attempts in young people using SSRIs but SSRIs' impact on risk for suicides in youth is not well-established. Is there indication that SSRIs might raise risk for suicide attempts in young people? We used an observational register-based historical cohort design, a large cohort of all Danish individuals born in 1983-1989 (n = 392,458) and a propensity score approach to analyse the impact from SSRIs on risk for suicide attempts. Every suicide attempt and redeemed prescription of SSRIs was analysed by Cox regression. We found a significant overlap between redeeming a prescription on SSRIs and subsequent suicide attempt. The risk for suicide attempt was highest in the first 3 months after redeeming the first prescription. The hazard ratio for suicide attempts after redeeming a prescription was estimated to 5.23, 95% CI 4.82-5.68. We conclude that the risk of suicide attempt is higher for young people in the first months after redeeming their first prescription for SSRIs, compared to non-users. For SSRI users with lower propensity score (fewer risk factors for SSRIs) the risk of suicide attempt is estimated to be highest. Although the design may miss some explicit reason for prescription of SSRIs and SSRIs might be a marker for those in high risk rather than a causal risk factor, we would recommend systematic risk assessment in the period after redeeming the first prescription.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

PubMed

Guyon, Laurent; Lajaunie, Christian; Fer, Frédéric; Bhajun, Ricky; Sulpice, Eric; Pinna, Guillaume; Campalans, Anna; Radicella, J Pablo; Rouillier, Philippe; Mary, Mélissa; Combe, Stéphanie; Obeid, Patricia; Vert, Jean-Philippe; Gidrol, Xavier

2015-09-18

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

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

On the use and misuse of scalar scores of confounders in design and analysis of observational studies.

PubMed

Pfeiffer, R M; Riedl, R

2015-08-15

We assess the asymptotic bias of estimates of exposure effects conditional on covariates when summary scores of confounders, instead of the confounders themselves, are used to analyze observational data. First, we study regression models for cohort data that are adjusted for summary scores. Second, we derive the asymptotic bias for case-control studies when cases and controls are matched on a summary score, and then analyzed either using conditional logistic regression or by unconditional logistic regression adjusted for the summary score. Two scores, the propensity score (PS) and the disease risk score (DRS) are studied in detail. For cohort analysis, when regression models are adjusted for the PS, the estimated conditional treatment effect is unbiased only for linear models, or at the null for non-linear models. Adjustment of cohort data for DRS yields unbiased estimates only for linear regression; all other estimates of exposure effects are biased. Matching cases and controls on DRS and analyzing them using conditional logistic regression yields unbiased estimates of exposure effect, whereas adjusting for the DRS in unconditional logistic regression yields biased estimates, even under the null hypothesis of no association. Matching cases and controls on the PS yield unbiased estimates only under the null for both conditional and unconditional logistic regression, adjusted for the PS. We study the bias for various confounding scenarios and compare our asymptotic results with those from simulations with limited sample sizes. To create realistic correlations among multiple confounders, we also based simulations on a real dataset. Copyright © 2015 John Wiley & Sons, Ltd.

Microbial fuel cell-based biosensor for toxic carbon monoxide monitoring.

PubMed

Zhou, Shaofeng; Huang, Shaobin; Li, Yi; Zhao, Nannan; Li, Han; Angelidaki, Irini; Zhang, Yifeng

2018-08-15

This study presents an innovative microbial fuel cell-based biosensor for carbon monoxide (CO) monitoring. The hypothesis for the function of the biosensor is that CO inhibits bacterial activity in the anode and thereby reduces electricity production. A mature electrochemically active biofilm on the anode was exposed to CO gas at varied concentrations. A proportional linear relationship (R 2 = 0.987) between CO concentration and voltage drop (0.8 to 24 mV) in the range of 10% and 70% of CO concentration was observed. Notably, no further decrease of voltage output was observed by with further increasing CO concentration over 70%. Besides, the response time of the biosensor was 1 h. The compact design and simple operation of the biosensor makes it easy to be integrated in existing CO-based industrial facilities either as a forewarning sensor for CO toxicity or even as an individual on-line monitoring device. Copyright © 2018 Elsevier B.V. All rights reserved.

Using Spider-Web Patterns To Determine Toxicity

NASA Technical Reports Server (NTRS)

Noever, David A.; Cronise, Raymond J.; Relwani, Rachna A.

1995-01-01

Method of determining toxicities of chemicals involves recording and analysis of spider-web patterns. Based on observation spiders exposed to various chemicals spin webs that differ, in various ways, from normal webs. Potential alternative to toxicity testing on higher animals.

The Flipside of the Power of Engineered T Cells: Observed and Potential Toxicities of Genetically Modified T Cells as Therapy.

PubMed

Bedoya, Felipe; Frigault, Matthew J; Maus, Marcela V

2017-02-01

Autologous T cells modified to recognize novel antigen targets are a novel form of therapy for cancer. We review the various potential forms of observed and hypothetical toxicities associated with genetically modified T cells. Despite the focus on toxicities in this review, re-directed T cells represent a powerful and highly effective form of anti-cancer therapy; we remain optimistic that the common toxicities will become routinely manageable and that some theoretical toxicity will be exceedingly rare, if ever observed. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

TOWARDS REFINED USE OF TOXICITY DATA IN STATISTICALLY BASED SAR MODELS FOR DEVELOPMENTAL TOXICITY.

EPA Science Inventory

In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

AQUIRE: Aquatic Toxicity Information Retrieval data base. Data file

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

Anderson, E.; Pilli, A.

The purpose of Aquatic Toxicity Information Retrieval (AQUIRE) data base is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for AQUIRE. Independently compiled data files that meet AQUIRE parameter and quality assurance criteria are also included. Selected toxicity-test results and related testing information for any individual chemical from laboratory and field aquatic toxicity tests are extracted and added to AQUIRE. Acute, sublethal, and bioconcentration effects are included for tests withmore » freshwater and marine organisms. The total number of data records in AQUIRE now equals 104,500. This includes data from 6000 references, for 5200 chemicals and 2400 test species. A major data file, Acute Toxicity of Organic Chemicals (ATOC), has been incorporated into AQUIRE. The ATOC file contains laboratory acute test data on 525 organic chemicals using juvenile fathead minnows. The complete data file can be accessed by requesting review code 5 as a search parameter.« less

Toxicities and risk assessment of heavy metals in sediments of Taihu Lake, China, based on sediment quality guidelines.

PubMed

Zhang, Yanfeng; Han, Yuwei; Yang, Jinxi; Zhu, Lingyan; Zhong, Wenjue

2017-12-01

The occurrence, toxicities, and ecological risks of five heavy metals (Pb, Cu, Cd, Zn and Ni) in the sediment of Taihu Lake were investigated in this study. To evaluate the toxicities caused by the heavy metals, the toxicities induced by organic contaminants and ammonia in the sediments were screened out with activated carbon and zeolite. The toxicities of heavy metals in sediments were tested with benthic invertebrates (tubificid and chironomid). The correlations between toxicity of sediment and the sediment quality guidelines (SQGs) derived previously were evaluated. There were significant correlations (p<0.0001) between the observed toxicities and the total risk quotients of the heavy metals based on SQGs, indicating that threshold effect level (TEL) and probable effect level (PEL) were reliable to predict the toxicities of heavy metals in the sediments of Taihu Lake. By contrast, the method based on acid volatile sulfides (AVS) and simultaneously extracted metals (SEM), such as ∑SEM/AVS and ∑SEM-AVS, did not show correlations with the toxicities. Moreover, the predictive ability of SQGs was confirmed by a total predicting accuracy of 77%. Ecological risk assessment based on TELs and PELs showed that the contaminations of Pb, Cu, Cd and Zn in the sediments of Taihu Lake were at relatively low or medium levels. The risks caused by heavy metals in the sediments of northern bay of the lake, which received more wastewater discharge from upper stream, were higher than other area of the lake. Copyright © 2017. Published by Elsevier B.V.

Immunization-based scores as independent prognostic predictors in soft tissue sarcoma patients

PubMed Central

Jiang, Shan-Shan; Jiang, Long; Weng, De-Sheng; Li, Yuan-fang; Pan, Qiu-Zhong; Zhao, Jing-Jing; Tang, Yan; Zhou, Zhi-Wei; Xia, Jian-Chuan

2017-01-01

Background: The purpose of this study was to examine and compare the prognostic value of different immunization-based scoring systems in patients with soft tissue sarcoma (STS). Methods: We conducted a retrospective study evaluating a cohort of 165 patients diagnosed with STS between July 2007 and July 2014. The relative Glasgow prognostic score (GPS) of these patients was calculated using 3 different systems: the traditional GPS system (tGPS), the modified GPS system 1 (m1GPS), and the modified GPS system 2 (m2GPS). Then, we evaluated the relationships between each GPS system and clinicopathological characteristics. The mean follow-up for survivors in the cohort was 73.7 months as of March 2015. Results: The most favorable overall survival (OS) rate was associated with the score 0 groups, and the poorest progression-free survival (PFS) rate was associated with the score 2 groups, regardless of which system was used to calculate the score. Specifically, the m1GPS provided the greatest accuracy in predicting OS and PFS. Moreover, the same effect was observed in a separate analysis restricted to patients with metastases. Remarkably, in patients with a score of 2 as measured by all 3 systems, local treatment resulted in a poorer prognosis compared to patients with a score of 2 who did not receive local treatment. Conclusion: The GPS is a valuable prognostic marker and has the capability to predict the appropriate treatment strategy for STS patients with metastases. The modified GPS systems demonstrated superior prognostic and predictive value compared with the traditional GPS system. PMID:28367240

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

PubMed Central

Guyon, Laurent; Lajaunie, Christian; fer, Frédéric; bhajun, Ricky; sulpice, Eric; pinna, Guillaume; campalans, Anna; radicella, J. Pablo; rouillier, Philippe; mary, Mélissa; combe, Stéphanie; obeid, Patricia; vert, Jean-Philippe; gidrol, Xavier

2015-01-01

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection. PMID:26382112

Standardized Computer-based Organized Reporting of EEG: SCORE

PubMed Central

Beniczky, Sándor; Aurlien, Harald; Brøgger, Jan C; Fuglsang-Frederiksen, Anders; Martins-da-Silva, António; Trinka, Eugen; Visser, Gerhard; Rubboli, Guido; Hjalgrim, Helle; Stefan, Hermann; Rosén, Ingmar; Zarubova, Jana; Dobesberger, Judith; Alving, Jørgen; Andersen, Kjeld V; Fabricius, Martin; Atkins, Mary D; Neufeld, Miri; Plouin, Perrine; Marusic, Petr; Pressler, Ronit; Mameniskiene, Ruta; Hopfengärtner, Rüdiger; Emde Boas, Walter; Wolf, Peter

2013-01-01

The electroencephalography (EEG) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis of the recordings. The interobserver agreement in EEG interpretation is only moderate. This is partly due to the method of reporting the findings in free-text format. The purpose of our endeavor was to create a computer-based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video-EEG recordings). A working group of EEG experts took part in consensus workshops in Dianalund, Denmark, in 2010 and 2011. The faculty was approved by the Commission on European Affairs of the International League Against Epilepsy (ILAE). The working group produced a consensus proposal that went through a pan-European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer-based Organised Reporting of EEG (SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, “episodes” (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. The following specific aspects of the neonatal EEGs are scored: alertness, temporal organization, and spatial organization. For each EEG finding, relevant features are scored using predefined terms. Definitions are provided for all EEG terms and features. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer-assisted analysis into the report, it will make

Aquatic Toxicity Screening of an ACWA Secondary Waste, GB-Hydrolysate

DTIC Science & Technology

2009-01-01

Toxicity Comparison for GB-hydrolysates, Acetone, and Malathion Using O’Bryan and Ross Chemical Scoring System for Hazard and Exposure Identification ...hydrolysates, Acetone, and Malathion Using O’Bryan and Ross Chemical Scoring System for Hazard and Exposure Identification (5) and the U.S. Fish and...WWTF) or a TSDF. The toxicity results were ranked using the Chemical Scoring System for Hazard and Exposure Identification (5). This system is

Co-Attention Based Neural Network for Source-Dependent Essay Scoring

ERIC Educational Resources Information Center

Zhang, Haoran; Litman, Diane

2018-01-01

This paper presents an investigation of using a co-attention based neural network for source-dependent essay scoring. We use a co-attention mechanism to help the model learn the importance of each part of the essay more accurately. Also, this paper shows that the co-attention based neural network model provides reliable score prediction of…

Cell culture-based biosensing techniques for detecting toxicity in water.

PubMed

Tan, Lu; Schirmer, Kristin

2017-06-01

The significant increase of contaminants entering fresh water bodies calls for the development of rapid and reliable methods to monitor the aquatic environment and to detect water toxicity. Cell culture-based biosensing techniques utilise the overall cytotoxic response to external stimuli, mediated by a transduced signal, to specify the toxicity of aqueous samples. These biosensing techniques can effectively indicate water toxicity for human safety and aquatic organism health. In this review we account for the recent developments of the mainstream cell culture-based biosensing techniques for water quality evaluation, discuss their key features, potentials and limitations, and outline the future prospects of their development. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Estimation of a Preference-Based Summary Score for the Patient-Reported Outcomes Measurement Information System: The PROMIS®-Preference (PROPr) Scoring System.

PubMed

Dewitt, Barry; Feeny, David; Fischhoff, Baruch; Cella, David; Hays, Ron D; Hess, Rachel; Pilkonis, Paul A; Revicki, Dennis A; Roberts, Mark S; Tsevat, Joel; Yu, Lan; Hanmer, Janel

2018-06-01

Health-related quality of life (HRQL) preference-based scores are used to assess the health of populations and patients and for cost-effectiveness analyses. The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS ® ) consists of patient-reported outcome measures developed using item response theory. PROMIS is in need of a direct preference-based scoring system for assigning values to health states. To produce societal preference-based scores for 7 PROMIS domains: Cognitive Function-Abilities, Depression, Fatigue, Pain Interference, Physical Function, Sleep Disturbance, and Ability to Participate in Social Roles and Activities. Online survey of a US nationally representative sample ( n = 983). Preferences for PROMIS health states were elicited with the standard gamble to obtain both single-attribute scoring functions for each of the 7 PROMIS domains and a multiplicative multiattribute utility (scoring) function. The 7 single-attribute scoring functions were fit using isotonic regression with linear interpolation. The multiplicative multiattribute summary function estimates utilities for PROMIS multiattribute health states on a scale where 0 is the utility of being dead and 1 the utility of "full health." The lowest possible score is -0.022 (for a state viewed as worse than dead), and the highest possible score is 1. The online survey systematically excludes some subgroups, such as the visually impaired and illiterate. A generic societal preference-based scoring system is now available for all studies using these 7 PROMIS health domains.

Performance of toxicity probability interval based designs in contrast to the continual reassessment method

PubMed Central

Horton, Bethany Jablonski; Wages, Nolan A.; Conaway, Mark R.

2016-01-01

Toxicity probability interval designs have received increasing attention as a dose-finding method in recent years. In this study, we compared the two-stage, likelihood-based continual reassessment method (CRM), modified toxicity probability interval (mTPI), and the Bayesian optimal interval design (BOIN) in order to evaluate each method's performance in dose selection for Phase I trials. We use several summary measures to compare the performance of these methods, including percentage of correct selection (PCS) of the true maximum tolerable dose (MTD), allocation of patients to doses at and around the true MTD, and an accuracy index. This index is an efficiency measure that describes the entire distribution of MTD selection and patient allocation by taking into account the distance between the true probability of toxicity at each dose level and the target toxicity rate. The simulation study considered a broad range of toxicity curves and various sample sizes. When considering PCS, we found that CRM outperformed the two competing methods in most scenarios, followed by BOIN, then mTPI. We observed a similar trend when considering the accuracy index for dose allocation, where CRM most often outperformed both the mTPI and BOIN. These trends were more pronounced with increasing number of dose levels. PMID:27435150

Association of a Dietary Score with Incident Type 2 Diabetes: The Dietary-Based Diabetes-Risk Score (DDS)

PubMed Central

Dominguez, Ligia J.; Bes-Rastrollo, Maira; Basterra-Gortari, Francisco Javier; Gea, Alfredo; Barbagallo, Mario; Martínez-González, Miguel A.

2015-01-01

Background Strong evidence supports that dietary modifications may decrease incident type 2 diabetes mellitus (T2DM). Numerous diabetes risk models/scores have been developed, but most do not rely specifically on dietary variables or do not fully capture the overall dietary pattern. We prospectively assessed the association of a dietary-based diabetes-risk score (DDS), which integrates optimal food patterns, with the risk of developing T2DM in the SUN (“Seguimiento Universidad de Navarra”) longitudinal study. Methods We assessed 17,292 participants initially free of diabetes, followed-up for a mean of 9.2 years. A validated 136-item FFQ was administered at baseline. Taking into account previous literature, the DDS positively weighted vegetables, fruit, whole cereals, nuts, coffee, low-fat dairy, fiber, PUFA, and alcohol in moderate amounts; while it negatively weighted red meat, processed meats and sugar-sweetened beverages. Energy-adjusted quintiles of each item (with exception of moderate alcohol consumption that received either 0 or 5 points) were used to build the DDS (maximum: 60 points). Incident T2DM was confirmed through additional detailed questionnaires and review of medical records of participants. We used Cox proportional hazards models adjusted for socio-demographic and anthropometric parameters, health-related habits, and clinical variables to estimate hazard ratios (HR) of T2DM. Results We observed 143 T2DM confirmed cases during follow-up. Better baseline conformity with the DDS was associated with lower incidence of T2DM (multivariable-adjusted HR for intermediate (25–39 points) vs. low (11–24) category 0.43 [95% confidence interval (CI) 0.21, 0.89]; and for high (40–60) vs. low category 0.32 [95% CI: 0.14, 0.69]; p for linear trend: 0.019). Conclusions The DDS, a simple score exclusively based on dietary components, showed a strong inverse association with incident T2DM. This score may be applicable in clinical practice to improve

Synthesis, molecular docking, antimicrobial, antioxidant and toxicity assessment of quinoline peptides.

PubMed

Thangaraj, Muthu; Gengan, Robert Moonsamy; Ranjan, Bibhuti; Muthusamy, Ramesh

2018-01-01

A series of quinoline based peptides were synthesized by a one-pot reaction through Ugi-four component condensation of lipoic acid, cyclohexyl isocyanide, aniline derivatives and 2-methoxy quinoline-3-carbaldehyde derivatives under microwave irradiation. The products were obtained in excellent yields and high purity. Solvent optimization and the effect of microwave irradiation with various powers were also observed. All the synthesized compounds were characterized by FTIR, NMR spectral data and elemental analysis. A total of eight peptides were subjected to antimicrobial, antioxidant and toxicity evaluation. Among them, four peptides showed potential towards antibacterial screening with Bacillus cereus, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis and Candida albicans, Candida utilis and three peptides showed antioxidant test positive (DPPH). Besides, toxicity of all the peptides were evaluated by using brine shrimp and it was observed that four peptides showed mortality rate less than 50% up to 48h. Molecular docking studies revealed that the higher binding affinity of the two peptides toward DNA gyrase than ciprofloxacin based on Libdock score. The described chemistry represents a facile tool to synthesize complex heterocycles of pharmaceutical relevance in a highly efficient and one-pot fashion. The advantages of this method are its green approach, inexpensive solvent, shorter reaction times and excellent yields. Copyright © 2017 Elsevier B.V. All rights reserved.

Propensity score models in observational comparative effectiveness studies: cornerstone of design or statistical afterthought?

PubMed

Robinson, John W

2012-03-01

Propensity score models are increasingly used in observational comparative effectiveness studies to reduce confounding by covariates that are associated with both a study outcome and treatment choice. Any such potentially confounding covariate will bias estimation of the effect of treatment on the outcome, unless the distribution of that covariate is well-balanced between treatment and control groups. Constructing a subsample of treated and control subjects who are matched on estimated propensity scores is a means of achieving such balance for covariates that are included in the propensity score model. If, during study design, investigators assemble a comprehensive inventory of known and suspected potentially confounding covariates, examination of how well this inventory is covered by the chosen dataset yields an assessment of the extent of bias reduction that is possible by matching on estimated propensity scores. These considerations are explored by examining the designs of three recently published comparative effectiveness studies.

Feature and Score Fusion Based Multiple Classifier Selection for Iris Recognition

PubMed Central

Islam, Md. Rabiul

2014-01-01

The aim of this work is to propose a new feature and score fusion based iris recognition approach where voting method on Multiple Classifier Selection technique has been applied. Four Discrete Hidden Markov Model classifiers output, that is, left iris based unimodal system, right iris based unimodal system, left-right iris feature fusion based multimodal system, and left-right iris likelihood ratio score fusion based multimodal system, is combined using voting method to achieve the final recognition result. CASIA-IrisV4 database has been used to measure the performance of the proposed system with various dimensions. Experimental results show the versatility of the proposed system of four different classifiers with various dimensions. Finally, recognition accuracy of the proposed system has been compared with existing N hamming distance score fusion approach proposed by Ma et al., log-likelihood ratio score fusion approach proposed by Schmid et al., and single level feature fusion approach proposed by Hollingsworth et al. PMID:25114676

Feature and score fusion based multiple classifier selection for iris recognition.

PubMed

Islam, Md Rabiul

2014-01-01

The aim of this work is to propose a new feature and score fusion based iris recognition approach where voting method on Multiple Classifier Selection technique has been applied. Four Discrete Hidden Markov Model classifiers output, that is, left iris based unimodal system, right iris based unimodal system, left-right iris feature fusion based multimodal system, and left-right iris likelihood ratio score fusion based multimodal system, is combined using voting method to achieve the final recognition result. CASIA-IrisV4 database has been used to measure the performance of the proposed system with various dimensions. Experimental results show the versatility of the proposed system of four different classifiers with various dimensions. Finally, recognition accuracy of the proposed system has been compared with existing N hamming distance score fusion approach proposed by Ma et al., log-likelihood ratio score fusion approach proposed by Schmid et al., and single level feature fusion approach proposed by Hollingsworth et al.

Statistical Assessment of Estimated Transformations in Observed-Score Equating

ERIC Educational Resources Information Center

Wiberg, Marie; González, Jorge

2016-01-01

Equating methods make use of an appropriate transformation function to map the scores of one test form into the scale of another so that scores are comparable and can be used interchangeably. The equating literature shows that the ways of judging the success of an equating (i.e., the score transformation) might differ depending on the adopted…

XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients

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

Seibold, Petra; Behrens, Sabine; Schmezer, Peter

Purpose: To identify single-nucleotide polymorphisms (SNPs) in oxidative stress–related genes associated with risk of late toxicities in breast cancer patients receiving radiation therapy. Methods and Materials: Using a 2-stage design, 305 SNPs in 59 candidate genes were investigated in the discovery phase in 753 breast cancer patients from 2 prospective cohorts from Germany. The 10 most promising SNPs in 4 genes were evaluated in the replication phase in up to 1883 breast cancer patients from 6 cohorts identified through the Radiogenomics Consortium. Outcomes of interest were late skin toxicity and fibrosis of the breast, as well as an overall toxicity score (Standardized Totalmore » Average Toxicity). Multivariable logistic and linear regression models were used to assess associations between SNPs and late toxicity. A meta-analysis approach was used to summarize evidence. Results: The association of a genetic variant in the base excision repair gene XRCC1, rs2682585, with normal tissue late radiation toxicity was replicated in all tested studies. In the combined analysis of discovery and replication cohorts, carrying the rare allele was associated with a significantly lower risk of skin toxicities (multivariate odds ratio 0.77, 95% confidence interval 0.61-0.96, P=.02) and a decrease in Standardized Total Average Toxicity scores (−0.08, 95% confidence interval −0.15 to −0.02, P=.016). Conclusions: Using a stage design with replication, we identified a variant allele in the base excision repair gene XRCC1 that could be used in combination with additional variants for developing a test to predict late toxicities after radiation therapy in breast cancer patients.« less

Weighted Feature Significance: A Simple, Interpretable Model of Compound Toxicity Based on the Statistical Enrichment of Structural Features

PubMed Central

Huang, Ruili; Southall, Noel; Xia, Menghang; Cho, Ming-Hsuang; Jadhav, Ajit; Nguyen, Dac-Trung; Inglese, James; Tice, Raymond R.; Austin, Christopher P.

2009-01-01

In support of the U.S. Tox21 program, we have developed a simple and chemically intuitive model we call weighted feature significance (WFS) to predict the toxicological activity of compounds, based on the statistical enrichment of structural features in toxic compounds. We trained and tested the model on the following: (1) data from quantitative high–throughput screening cytotoxicity and caspase activation assays conducted at the National Institutes of Health Chemical Genomics Center, (2) data from Salmonella typhimurium reverse mutagenicity assays conducted by the U.S. National Toxicology Program, and (3) hepatotoxicity data published in the Registry of Toxic Effects of Chemical Substances. Enrichments of structural features in toxic compounds are evaluated for their statistical significance and compiled into a simple additive model of toxicity and then used to score new compounds for potential toxicity. The predictive power of the model for cytotoxicity was validated using an independent set of compounds from the U.S. Environmental Protection Agency tested also at the National Institutes of Health Chemical Genomics Center. We compared the performance of our WFS approach with classical classification methods such as Naive Bayesian clustering and support vector machines. In most test cases, WFS showed similar or slightly better predictive power, especially in the prediction of hepatotoxic compounds, where WFS appeared to have the best performance among the three methods. The new algorithm has the important advantages of simplicity, power, interpretability, and ease of implementation. PMID:19805409

Safety Evaluation of Silk Protein Film (A Novel Wound Healing Agent) in Terms of Acute Dermal Toxicity, Acute Dermal Irritation and Skin Sensitization

PubMed Central

Padol, Amol R.; Jayakumar, K.; Shridhar, N. B.; Narayana Swamy, H. D.; Narayana Swamy, M.; Mohan, K.

2011-01-01

Acute dermal toxicity study was conducted in rats. The parameters studied were body weight, serum biochemistry and gross pathology. The animals were also observed for clinical signs and mortality after the application of test film. The dermal irritation potential of silk protein film was examined using Draize test. In the initial test, three test patches were applied sequentially for 3 min, 1 and 4 hours, respectively, and skin reaction was graded. The irritant or negative response was confirmed using two additional animals, each with one patch, for an exposure period of 4 hours. The responses were scored at 1, 24, 48 and 72 hours after the patch removal. Skin sensitization study was conducted according to Buehler test in guinea pigs, in which on day 0, 7 and 14, the animals were exposed to test material for 6 hours (Induction phase) and on day 28, the animals were exposed for a period of 24 hours (Challenge phase). The skin was observed and recorded at 24 and 48 hours after the patch removal. In acute dermal toxicity study, the rats dermally treated with silk film did not show any abnormal clinical signs and the body weight, biochemical parameters and gross pathological observations were not significantly different from the control group. In acute dermal irritation study, the treated rabbits showed no signs of erythema, edema and eschar, and the scoring was given as “0” for all time points of observations according to Draize scoring system. In skin sensitization study, there were no skin reactions 24 and 48 hours after the removal of challenge patch, which was scored “0” based on Magnusson/Kligman grading scale. PMID:21430915

SYNTAX score based on coronary computed tomography angiography may have a prognostic value in patients with complex coronary artery disease: An observational study from a retrospective cohort.

PubMed

Suh, Young Joo; Han, Kyunghwa; Chang, Suyon; Kim, Jin Young; Im, Dong Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Hur, Jin; Kim, Young Jin; Choi, Byoung Wook

2017-09-01

The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score is an invasive coronary angiography (ICA)-based score for quantifying the complexity of coronary artery disease (CAD). Although the SYNTAX score was originally developed based on ICA, recent publications have reported that coronary computed tomography angiography (CCTA) is a feasible modality for the estimation of the SYNTAX score.The aim of our study was to investigate the prognostic value of the SYNTAX score, based on CCTA for the prediction of major adverse cardiac and cerebrovascular events (MACCEs) in patients with complex CAD.The current study was approved by the institutional review board of our institution, and informed consent was waived for this retrospective cohort study. We included 251 patients (173 men, mean age 66.0 ± 9.29 years) who had complex CAD [3-vessel disease or left main (LM) disease] on CCTA. SYNTAX score was obtained on the basis of CCTA. Follow-up clinical outcome data regarding composite MACCEs were also obtained. Cox proportional hazards models were developed to predict the risk of MACCEs based on clinical variables, treatment, and computed tomography (CT)-SYNTAX scores.During the median follow-up period of 1517 days, there were 48 MACCEs. Univariate Cox hazards models demonstrated that MACCEs were associated with advanced age, low body mass index (BMI), and dyslipidemia (P < .2). In patients with LM disease, MACCEs were associated with a higher SYNTAX score. In patients with CT-SYNTAX score ≥23, patients who underwent coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention had significantly lower hazard ratios than patients who were treated with medication alone. In multivariate Cox hazards model, advanced age, low BMI, and higher SYNTAX score showed an increased hazard ratio for MACCE, while treatment with CABG showed a lower hazard ratio (P < .2).On the basis of our results, CT-SYNTAX score

Anomalous diffusion in the evolution of soccer championship scores: Real data, mean-field analysis, and an agent-based model

NASA Astrophysics Data System (ADS)

da Silva, Roberto; Vainstein, Mendeli H.; Gonçalves, Sebastián; Paula, Felipe S. F.

2013-08-01

Statistics of soccer tournament scores based on the double round robin system of several countries are studied. Exploring the dynamics of team scoring during tournament seasons from recent years we find evidences of superdiffusion. A mean-field analysis results in a drift velocity equal to that of real data but in a different diffusion coefficient. Along with the analysis of real data we present the results of simulations of soccer tournaments obtained by an agent-based model which successfully describes the final scoring distribution [da Silva , Comput. Phys. Commun.CPHCBZ0010-465510.1016/j.cpc.2012.10.030 184, 661 (2013)]. Such model yields random walks of scores over time with the same anomalous diffusion as observed in real data.

Toxicities of glyphosate- and cypermethrin-based pesticides are antagonic in the tenspotted livebearer fish (Cnesterodon decemmaculatus).

PubMed

Brodeur, Julie Céline; Malpel, Solène; Anglesio, Ana Belén; Cristos, Diego; D'Andrea, María Florencia; Poliserpi, María Belén

2016-07-01

Although pesticide contamination of surface waters normally occurs in the form of mixtures, the toxicity and interactions displayed by such mixtures have been little characterized until now. The present study examined the interactions prevailing in equitoxic and non-equitoxic binary mixtures of formulations of glyphosate (Glifoglex(®)) and cypermethrin (Glextrin(®)) to the tenspotted livebearer (Cnesterodon decemmaculatus), a widely distributed South American fish. The following 96 h-LC50s were obtained when pesticide formulations were tested individually: Glifoglex(®) 41.4 and 53 mg ae glyphosate/L; Glextrin(®) 1.89 and 2.60 μg cypermethrin/L. Equitoxic and non-equitoxic mixtures were significantly antagonic in all combinations tested. The magnitude of the antagonism (factor by which toxicity differed from concentration addition) varied between 1.37 and 3.09 times in the different non-equitoxic mixtures tested. Antagonism was due to a strong inhibition of cypermethrin toxicity by the glyphosate formulation, the toxicity of the cypermethrin-based pesticide being almost completely overridden by the glyphosate formulation. Results obtained in the current study with fish are radically opposite to those previously observed in tadpoles where synergy was observed when Glifoglex(®) and Glextrin(®) were present in mixtures (Brodeur et al., 2014). Copyright © 2016 Elsevier Ltd. All rights reserved.

A urinary biomarker-based risk score correlates with multiparametric MRI for prostate cancer detection.

PubMed

Hendriks, Rianne J; van der Leest, Marloes M G; Dijkstra, Siebren; Barentsz, Jelle O; Van Criekinge, Wim; Hulsbergen-van de Kaa, Christina A; Schalken, Jack A; Mulders, Peter F A; van Oort, Inge M

2017-10-01

Prostate cancer (PCa) diagnostics would greatly benefit from more accurate, non-invasive techniques for the detection of clinically significant disease, leading to a reduction of over-diagnosis and over-treatment. The aim of this study was to determine the association between a novel urinary biomarker-based risk score (SelectMDx), multiparametric MRI (mpMRI) outcomes, and biopsy results for PCa detection. This retrospective observational study used data from the validation study of the SelectMDx score, in which urine was collected after digital rectal examination from men undergoing prostate biopsies. A subset of these patients also underwent a mpMRI scan of the prostate. The indications for performing mpMRI were based on persistent clinical suspicion of PCa or local staging after PCa was found upon biopsy. All mpMRI images were centrally reviewed in 2016 by an experienced radiologist blinded for the urine test results and biopsy outcome. The PI-RADS version 2 was used. In total, 172 patients were included for analysis. Hundred (58%) patients had PCa detected upon prostate biopsy, of which 52 (52%) had high-grade disease correlated with a significantly higher SelectMDx score (P < 0.01). The median SelectMDx score was significantly higher in patients with a suspicious significant lesion on mpMRI compared to no suspicion of significant PCa (P < 0.01). For the prediction of mpMRI outcome, the area-under-the-curve of SelectMDx was 0.83 compared to 0.66 for PSA and 0.65 for PCA3. There was a positive association between SelectMDx score and the final PI-RADS grade. There was a statistically significant difference in SelectMDx score between PI-RADS 3 and 4 (P < 0.01) and between PI-RADS 4 and 5 (P < 0.01). The novel urinary biomarker-based SelectMDx score is a promising tool in PCa detection. This study showed promising results regarding the correlation between the SelectMDx score and mpMRI outcomes, outperforming PCA3. Our results suggest that this risk

Etanercept therapy for toxic epidermal necrolysis.

PubMed

Paradisi, Andrea; Abeni, Damiano; Bergamo, Fabio; Ricci, Francesco; Didona, Dario; Didona, Biagio

2014-08-01

Toxic epidermal necrolysis (TEN) is a severe and potentially lethal drug reaction for which no standard treatment is available. To describe a case series of patients with TEN treated with a single dose of etanercept. We observed 10 consecutive patients with TEN. For each patient, we recorded the presence of comorbidities and all the drugs recently started (ie, in the last month). In all cases, 50 mg of etanercept was administered in a single subcutaneous injection. The clinical severity of disease was computed using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Using the probabilities of death linked to each level of SCORTEN score, we calculated the expected probability of death in our patients. Healing was defined as complete reepithelialization, and a time to healing curve was then obtained using the Kaplan-Meier method. All patients promptly responded to treatment, reaching complete reepithelialization without complications or side effects. The median time to healing was 8.5 days. This is a small, uncontrolled case series. These preliminary results suggest the possibility that tumor necrosis factor-alfa may be an effective target for control of TEN, a dangerous skin condition for which no effective cure has yet been found. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

NASA Astrophysics Data System (ADS)

Nam, I. F.; Zhuk, V. V.

2015-04-01

Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

Effects of Body-Mind Training and Relaxation Stretching on Persons with Chronic Toxic Encephalopathy.

ERIC Educational Resources Information Center

Engel, Lis; Andersen, Lars Bo

2000-01-01

Investigates the psychological and physical effects of training of body awareness and slow stretching on persons (N=8) with chronic toxic encephalopathy. Results show that electromyography on the frontalis muscle and state anxiety decreased, but no changes were observed in trait anxiety and in the creativity score. (Author/MKA)

A new approach for modeling patient overall radiosensitivity and predicting multiple toxicity endpoints for breast cancer patients.

PubMed

Mbah, Chamberlain; De Ruyck, Kim; De Schrijver, Silke; De Sutter, Charlotte; Schiettecatte, Kimberly; Monten, Chris; Paelinck, Leen; De Neve, Wilfried; Thierens, Hubert; West, Catharine; Amorim, Gustavo; Thas, Olivier; Veldeman, Liv

2018-05-01

Evaluation of patient characteristics inducing toxicity in breast radiotherapy, using simultaneous modeling of multiple endpoints. In 269 early-stage breast cancer patients treated with whole-breast irradiation (WBI) after breast-conserving surgery, toxicity was scored, based on five dichotomized endpoints. Five logistic regression models were fitted, one for each endpoint and the effect sizes of all variables were estimated using maximum likelihood (MLE). The MLEs are improved with James-Stein estimates (JSEs). The method combines all the MLEs, obtained for the same variable but from different endpoints. Misclassification errors were computed using MLE- and JSE-based prediction models. For associations, p-values from the sum of squares of MLEs were compared with p-values from the Standardized Total Average Toxicity (STAT) Score. With JSEs, 19 highest ranked variables were predictive of the five different endpoints. Important variables increasing radiation-induced toxicity were chemotherapy, age, SATB2 rs2881208 SNP and nodal irradiation. Treatment position (prone position) was most protective and ranked eighth. Overall, the misclassification errors were 45% and 34% for the MLE- and JSE-based models, respectively. p-Values from the sum of squares of MLEs and p-values from STAT score led to very similar conclusions, except for the variables nodal irradiation and treatment position, for which STAT p-values suggested an association with radiosensitivity, whereas p-values from the sum of squares indicated no association. Breast volume was ranked as the most significant variable in both strategies. The James-Stein estimator was used for selecting variables that are predictive for multiple toxicity endpoints. With this estimator, 19 variables were predictive for all toxicities of which four were significantly associated with overall radiosensitivity. JSEs led to almost 25% reduction in the misclassification error rate compared to conventional MLEs. Finally, patient

[Inter-observes agreement of Ishak and Metavir scores in histological evaluation of chronic viral hepatitis B and C].

PubMed

Rammeh, Soumaya; Khadra, Hajer Ben; Znaidi, Nadia Sabbegh; Romdhane, Neila Attia; Najjar, Taoufik; Bouzaidi, Slim; Zermani, Rachida

2014-01-01

Many classification systems are currently used for histological evaluation of the severity of chronic viral hepatitis, including the Ishak and Metavir scores, but there is not a consensus classification. The objective of this work was to study the intra and inter-observers agreement of these two scores in the histopathological analysis of liver biopsies in patients with chronic viral hepatitis B or C. Fifty nine patients were included in the study, 26 had chronic hepatitis C and 33 had chronic hepatitis B. To investigate the inter-observers agreement, the liver biopsies were analyzed separately by two pathologists without prior consensus reading. The two pathologists conducted then a consensual reading before reviewing all cases independently. Cohen's kappa coefficient was calculated and in case of asymmetry Spearman's rho coefficient. Before the consensus reading, the agreement was moderate for the analysis of histological activity with both scores (Metavir: kappa=0.41, Ishak: rho=0.58). For the analysis of fibrosis, the agreement was good with both scores (Metavir: kappa=0.61, Ishak: rho=0.86). The consensus reading has improved the reproducibility of the activity that has become good with both scores (Metavir: kappa=0.77, Ishak: rho=0.76). For fibrosis improvement was observed with the Ishak score which agreement became excellent (kappa=0.81). In conclusion, we recommend in routine practice, a combined score: Metavir for activity and Ishak for fibrosis and to make a double reading for each biopsy.

A nationwide register-based survey of baclofen toxicity.

PubMed

Kiel, Louise Bendix; Hoegberg, Lotte Christine Groth; Jansen, Tejs; Petersen, John Asger; Dalhoff, Kim Peder

2015-05-01

To study the use and misuse (poisonings) of baclofen in the time period of 2007-2012 and to evaluate the severity and clinical symptoms of poisonings including ingested baclofen. The National Patient Register (NPR) was searched for admissions due to baclofen poisonings from 2007 to 2012. The search was conducted with ICD-10 codes for poisoning, self-harm and suicide, and coupled with the baclofen ATC code. All enquiries about baclofen to the Danish Poison Information Centre (DPIC) in the same period were evaluated. Demographic and clinical data were extracted, and the poisonings were classified according to the Poison Severity Score. The number of baclofen poisonings did not increase from 2007 to 2012. Thirty-eight admissions with baclofen poisoning were registered at the NPR; however, only one-third of the reviewed DPIC cases were registered at the NPR with the correct coding. In the group of severely poisoned patients (PSS 3), three patients had only ingested baclofen (mean 2000 mg; SD 500 mg) and eight patients had ingested baclofen together with alcohol or psychotropic drugs (mean 900 mg; SD 641 mg). All patients presented with deep coma and respiratory depression. Additionally, seizures and cardiovascular events (mild hypo- or hypertension and bradycardia) occurred. There is a substantial degree of underreporting of baclofen poisonings in Denmark. Symptoms of baclofen poisoning progress very fast, and toxicity was observed even with doses as low as 150 mg. We therefore recommend that observation and treatment of these patients should be carried out in an intermediate- or intensive care unit. The most important treatment is the maintenance of a protected airway and respiration. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Optimal protein library design using recombination or point mutations based on sequence-based scoring functions.

PubMed

Pantazes, Robert J; Saraf, Manish C; Maranas, Costas D

2007-08-01

In this paper, we introduce and test two new sequence-based protein scoring systems (i.e. S1, S2) for assessing the likelihood that a given protein hybrid will be functional. By binning together amino acids with similar properties (i.e. volume, hydrophobicity and charge) the scoring systems S1 and S2 allow for the quantification of the severity of mismatched interactions in the hybrids. The S2 scoring system is found to be able to significantly functionally enrich a cytochrome P450 library over other scoring methods. Given this scoring base, we subsequently constructed two separate optimization formulations (i.e. OPTCOMB and OPTOLIGO) for optimally designing protein combinatorial libraries involving recombination or mutations, respectively. Notably, two separate versions of OPTCOMB are generated (i.e. model M1, M2) with the latter allowing for position-dependent parental fragment skipping. Computational benchmarking results demonstrate the efficacy of models OPTCOMB and OPTOLIGO to generate high scoring libraries of a prespecified size.

The TRIAGE-ProADM Score for an Early Risk Stratification of Medical Patients in the Emergency Department - Development Based on a Multi-National, Prospective, Observational Study

PubMed Central

Hausfater, Pierre; Amin, Devendra; Amin, Adina; Canavaggio, Pauline; Sauvin, Gabrielle; Bernard, Maguy; Conca, Antoinette; Haubitz, Sebastian; Struja, Tristan; Huber, Andreas; Mueller, Beat; Schuetz, Philipp

2016-01-01

Introduction The inflammatory biomarker pro-adrenomedullin (ProADM) provides additional prognostic information for the risk stratification of general medical emergency department (ED) patients. The aim of this analysis was to develop a triage algorithm for improved prognostication and later use in an interventional trial. Methods We used data from the multi-national, prospective, observational TRIAGE trial including consecutive medical ED patients from Switzerland, France and the United States. We investigated triage effects when adding ProADM at two established cut-offs to a five-level ED triage score with respect to adverse clinical outcome. Results Mortality in the 6586 ED patients showed a step-wise, 25-fold increase from 0.6% to 4.5% and 15.4%, respectively, at the two ProADM cut-offs (≤0.75nmol/L, >0.75–1.5nmol/L, >1.5nmol/L, p ANOVA <0.0001). Risk stratification by combining ProADM within cut-off groups and the triage score resulted in the identification of 1662 patients (25.2% of the population) at a very low risk of mortality (0.3%, n = 5) and 425 patients (6.5% of the population) at very high risk of mortality (19.3%, n = 82). Risk estimation by using ProADM and the triage score from a logistic regression model allowed for a more accurate risk estimation in the whole population with a classification of 3255 patients (49.4% of the population) in the low risk group (0.3% mortality, n = 9) and 1673 (25.4% of the population) in the high-risk group (15.1% mortality, n = 252). Conclusions Within this large international multicenter study, a combined triage score based on ProADM and established triage scores allowed a more accurate mortality risk discrimination. The TRIAGE-ProADM score improved identification of both patients at the highest risk of mortality who may benefit from early therapeutic interventions (rule in), and low risk patients where deferred treatment without negatively affecting outcome may be possible (rule out). PMID:28005916

High virological suppression regardless of the genotypic susceptibility score after switching to a dolutegravir-based regimen: week 48 results in an observational cohort.

PubMed

Charpentier, Charlotte; Peytavin, Gilles; Lê, Minh P; Joly, Véronique; Cabras, Ornella; Perrier, Marine; Le Gac, Sylvie; Phung, Bao; Yazdanpanah, Yazdan; Descamps, Diane; Landman, Roland

2018-06-01

To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to a dolutegravir-based regimen, regardless of the genotypic susceptibility score (GSS). This was an observational single-centre study assessing ART-treated patients with plasma viral load (pVL) <50 copies/mL who were switched to a dolutegravir-based regimen with 1 year of follow-up. PCR negative was defined as an undetected PCR signal. Trough plasma concentration (C24) was determined using UPLC-MS/MS. Two hundred and thirty-nine patients initiated a dolutegravir-based regimen: 12%, 29% and 59% had a total GSS of 1 or 1.5 (group 1), 2 or 2.5 (group 2) and 3 (group 3), respectively. At switch initiation, the median time since first ART and the median duration with pVL <50 copies/mL were 13 years (IQR = 6-19) and 3 years (IQR = 1-6), respectively. Median times since last genotype were 9, 10 and 5 years for groups 1, 2 and 3, respectively. Twenty patients (8.4%) discontinued the dolutegravir-based regimen due to adverse events. During the study, 96.4% (n = 661/686) of all pVL were <50 copies/mL. Four patients (1.7%) experienced virological failure (two pVL >50 copies/mL) without emergence of resistance; these patients' GSSs were 2, 2.5, 3 and 3. The median dolutegravir C24 was 1545 ng/mL (IQR = 1150-2097). Of the patients with pVL <20 copies/mL, 72% were PCR negative during the follow-up, with no difference between the three groups of patients. This observational cohort study showed a high level of virological suppression maintenance in the first year following the switch to a dolutegravir-based regimen, even in patients with GSS ≤2.

Variability in the Results of Meta-Analysis as a Function of Comparing Effect Sizes Based on Scores from Noncomparable Measures: A Simulation Study

ERIC Educational Resources Information Center

Nugent, William R.

2017-01-01

Meta-analysis is a significant methodological advance that is increasingly important in research synthesis. Fundamental to meta-analysis is the presumption that effect sizes, such as the standardized mean difference (SMD), based on scores from different measures are comparable. It has been argued that population observed score SMDs based on scores…

Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement.

PubMed

Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

2012-01-01

Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). In vivo toxicity studies were performed in male balb 'C' mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement.

Urinary and Rectal Toxicity Profiles After Permanent Iodine-125 Implant Brachytherapy in Japanese Men: Nationwide J-POPS Multi-institutional Prospective Cohort Study

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

Ohashi, Toshio, E-mail: ohashi@rad.med.keio.ac.jp; Yorozu, Atsunori; Saito, Shiro

Purpose: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT). Methods and Materials: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiationmore » therapy. Results: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment. Conclusions: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other

Novel, customizable scoring functions, parameterized using N-PLS, for structure-based drug discovery.

PubMed

Catana, Cornel; Stouten, Pieter F W

2007-01-01

The ability to accurately predict biological affinity on the basis of in silico docking to a protein target remains a challenging goal in the CADD arena. Typically, "standard" scoring functions have been employed that use the calculated docking result and a set of empirical parameters to calculate a predicted binding affinity. To improve on this, we are exploring novel strategies for rapidly developing and tuning "customized" scoring functions tailored to a specific need. In the present work, three such customized scoring functions were developed using a set of 129 high-resolution protein-ligand crystal structures with measured Ki values. The functions were parametrized using N-PLS (N-way partial least squares), a multivariate technique well-known in the 3D quantitative structure-activity relationship field. A modest correlation between observed and calculated pKi values using a standard scoring function (r2 = 0.5) could be improved to 0.8 when a customized scoring function was applied. To mimic a more realistic scenario, a second scoring function was developed, not based on crystal structures but exclusively on several binding poses generated with the Flo+ docking program. Finally, a validation study was conducted by generating a third scoring function with 99 randomly selected complexes from the 129 as a training set and predicting pKi values for a test set that comprised the remaining 30 complexes. Training and test set r2 values were 0.77 and 0.78, respectively. These results indicate that, even without direct structural information, predictive customized scoring functions can be developed using N-PLS, and this approach holds significant potential as a general procedure for predicting binding affinity on the basis of in silico docking.

Morphology based scoring of chromosomal instability and its correlation with cell viability.

PubMed

Yadav, Shubhlata; Bhatia, Alka

2017-09-01

The aim of this study was to devise the quantitative scoring system for Chromosomal instability (CIN) based on morphological indicators like MPM, NB, NPB, CS, La and MN in cancer cell line and to correlate it with cell viability and death. Human hepatocellular carcinoma (HepG2) cells were treated with drugs like Diethylstilbestrol 0-100μM, Griseofulvin 0-40μg/ml, Vincristine sulphate 0-25μg/ml, Mitomycin C 0-600ng/ml, Bleomycin 0-10μg/ml, Doxorubicin 0-30μg/ml for 24h. Following this, the CIN was assessed by counting the morphological indicators like Micronuclei (MN), Nuclear Buds (NB), Nucleoplasmic bridges, Laggards, Multipolar mitosis and chromatin strings/1000 cells in Giemsa stained smears by light microscopy and by determining the percentage of aneuploid cells by flow cytometry. The cell viability was assessed by MTT assay and percentage of apoptotic cells was determined by flow cytometry. The MN and NB were most frequently seen indicators and main determinants of morphological CIN. However, the morphological CIN score did not show any correlation with cell viability and apoptosis. Aneuploidy however was found to correlate positively with cell viability and NB score in our study (P-value <0.05). The study for the 1st time attempted to develop a scoring system for CIN based on morphological parameters. However, a no correlation was observed between the later and cell viability or apoptosis. More robust techniques to quantify CIN may perhaps be more helpful in exploring the true link between CIN and cell viability in future. Copyright © 2017 Elsevier GmbH. All rights reserved.

Validity and Diagnostic Accuracy of Scores from the Autism Diagnostic Observation Schedule-Generic

ERIC Educational Resources Information Center

Reid, Melissa A.

2012-01-01

The purpose of this study was to examine the internal structure, relationships with other variables, and diagnostic accuracy of scores on the Autism Diagnostic Observation Schedule-Generic (ADOS-G; Lord et al., 1999) for the purpose of diagnostic decision-making. Participants were 462 children enrolled in a public school district in the southern…

Fat scoring: Sources of variability

USGS Publications Warehouse

Krementz, D.G.; Pendleton, G.W.

1990-01-01

Fat scoring is a widely used nondestructive method of assessing total body fat in birds. This method has not been rigorously investigated. We investigated inter- and intraobserver variability in scoring as well as the predictive ability of fat scoring using five species of passerines. Between-observer variation in scoring was variable and great at times. Observers did not consistently score species higher or lower relative to other observers nor did they always score birds with more total body fat higher. We found that within-observer variation was acceptable but was dependent on the species being scored. The precision of fat scoring was species-specific and for most species, fat scores accounted for less than 50% of the variation in true total body fat. Overall, we would describe fat scoring as a fairly precise method of indexing total body fat but with limited reliability among observers.

Identifying the causes of sediment-associated toxicity in urban waterways in South China: incorporating bioavailabillity-based measurements into whole-sediment toxicity identification evaluation.

PubMed

Yi, Xiaoyi; Li, Huizhen; Ma, Ping; You, Jing

2015-08-01

Sediments in urban waterways of Guangzhou, China, were contaminated by a variety of chemicals and showed prevalent toxicity to benthic organisms. A combination of whole-sediment toxicity identification evaluation (TIE) and bioavailability-based extraction was used to identify the causes of sediment toxicity. Of the 6 sediment samples collected, 4 caused 100% mortality to Chironomus dilutus in 10-d bioassays, and the potential toxicants were assessed using TIE in these sediments after dilution. The results of phase I characterization showed that organic contaminants were the principal contributors to the mortality of the midges in 2 sediments and that metals and organics jointly caused the mortality in the other 2 sediments. Ammonia played no role in the mortality for any samples. Conventional toxic unit analysis in phase II testing identified Cr, Cu, Ni, Pb, and Zn as the toxic metals, with cypermethrin, lambda-cyhalothrin, deltamethrin, and fipronils being the toxic organics. To improve the accuracy of identifying the toxicants, 4-step sequential extraction and Tenax extraction were conducted to analyze the bioavailability of the metals and organics, respectively. Bioavailable toxic unit analysis narrowed the list of toxic contributors, and the putative toxicants included 3 metals (Zn, Ni, and Pb) and 3 pesticides (cypermethrin, lambda-cyhalothrin, and fipronils). Metals contributed to the mortality in all sediments, but sediment dilution reduced the toxicity and confounded the characterization of toxicity contribution from metals in 2 sediments in phase I. Incorporating bioavailability-based measurements into whole-sediment TIE improved the accuracy of identifying the causative toxicants in urban waterways where multiple stressors occurred and contributed to sediment toxicity jointly. © 2015 SETAC.

Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study.

PubMed

Franco, Pierfrancesco; Potenza, Ilenia; Moretto, Francesco; Segantin, Mattia; Grosso, Mario; Lombardo, Antonello; Taricco, Daniela; Vallario, Patrizia; Filippi, Andrea Riccardo; Rampino, Monica; Ricardi, Umberto

2014-12-29

Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer. A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery. The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days. Holoil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic

dBBQs: dataBase of Bacterial Quality scores.

PubMed

Wanchai, Visanu; Patumcharoenpol, Preecha; Nookaew, Intawat; Ussery, David

2017-12-28

It is well-known that genome sequencing technologies are becoming significantly cheaper and faster. As a result of this, the exponential growth in sequencing data in public databases allows us to explore ever growing large collections of genome sequences. However, it is less known that the majority of available sequenced genome sequences in public databases are not complete, drafts of varying qualities. We have calculated quality scores for around 100,000 bacterial genomes from all major genome repositories and put them in a fast and easy-to-use database. Prokaryotic genomic data from all sources were collected and combined to make a non-redundant set of bacterial genomes. The genome quality score for each was calculated by four different measurements: assembly quality, number of rRNA and tRNA genes, and the occurrence of conserved functional domains. The dataBase of Bacterial Quality scores (dBBQs) was designed to store and retrieve quality scores. It offers fast searching and download features which the result can be used for further analysis. In addition, the search results are shown in interactive JavaScript chart framework using DC.js. The analysis of quality scores across major public genome databases find that around 68% of the genomes are of acceptable quality for many uses. dBBQs (available at http://arc-gem.uams.edu/dbbqs ) provides genome quality scores for all available prokaryotic genome sequences with a user-friendly Web-interface. These scores can be used as cut-offs to get a high-quality set of genomes for testing bioinformatics tools or improving the analysis. Moreover, all data of the four measurements that were combined to make the quality score for each genome, which can potentially be used for further analysis. dBBQs will be updated regularly and is freely use for non-commercial purpose.

Reliability of Total Test Scores When Considered as Ordinal Measurements

ERIC Educational Resources Information Center

Biswas, Ajoy Kumar

2006-01-01

This article studies the ordinal reliability of (total) test scores. This study is based on a classical-type linear model of observed score (X), true score (T), and random error (E). Based on the idea of Kendall's tau-a coefficient, a measure of ordinal reliability for small-examinee populations is developed. This measure is extended to large…

Assessing Toxicity of Obscurant Grade Pan-Based Carbon Fiber Aquatic Species Chronic Tests

DTIC Science & Technology

2004-12-01

ASSESSING TOXICITY OF OBSCURANT GRADE PAN-BASED CARBON FIBER: AQUATIC SPECIES CHRONIC TESTS N. A. Chester, M. V. Haley, C. W. Kurnas and R. T...with minimal restrictions. To this end we are investigating the toxicity of PAN-based carbon fibers to the aquatic species Ceriodaphnia dubia (water... toxicity methods to provide ecotoxicological results for both lethal and sub-lethal parameters, including LC50 (24-, 48- and 96-h), IC50, EC20, and

Improved synthesis of N-benzylaminoferrocene-based prodrugs and evaluation of their toxicity and antileukemic activity.

PubMed

Daum, Steffen; Chekhun, Vasiliy F; Todor, Igor N; Lukianova, Natalia Yu; Shvets, Yulia V; Sellner, Leopold; Putzker, Kerstin; Lewis, Joe; Zenz, Thorsten; de Graaf, Inge A M; Groothuis, Geny M M; Casini, Angela; Zozulia, Oleksii; Hampel, Frank; Mokhir, Andriy

2015-02-26

We report on an improved method of synthesis of N-benzylaminoferrocene-based prodrugs and demonstrate its applicability by preparing nine new aminoferrocenes. Their effect on the viability of selected cancer cells having different p53 status was studied. The obtained data are in agreement with the hypothesis that the toxicity of aminoferrocenes is not dependent upon p53 status. Subsequently the toxicity of a selected prodrug (4) was investigated ex vivo using rat precision cut liver slices and in vivo on hybrid male mice BDF1. In both experiments no toxicity was observed: ex vivo, up to 10 μM; in vivo, up to 6 mg/kg. Finally, prodrug 4 was shown to extend the survival of BDF1 mice carrying L1210 leukemia from 13.7 ± 0.6 days to 17.5 ± 0.7 days when injected daily 6 times at a dose of 26 μg/kg starting from the second day after injection of L1210 cells.

Toxicity of graphene nanoflakes evaluated by cell-based electrochemical impedance biosensing.

PubMed

Yoon, Ok Ja; Kim, Insu; Sohn, Il Yung; Kieu, Truong Thuy; Lee, Nae-Eung

2014-07-01

Graphene nanoflake toxicity was analyzed using cell-based electrochemical impedance biosensing with interdigitated indium tin oxide (ITO) electrodes installed in a custom-built mini-incubator positioned on an inverted optical microscope. Sensing with electrochemical measurements from interdigitated ITO electrodes was highly linear (R(2) = 0.93 and 0.96 for anodic peak current (Ipa) and cathodic peak current (Ipc), respectively). Size-dependent analysis of Graphene nanoflake toxicity was carried out in a mini-incubator system with cultured HeLa cells treated with Graphene nanoflakes having an average size of 80 or 30 nm for one day. Biological assays of cell proliferation and viability complemented electrochemical impedance measurements. The increased toxicity of smaller Graphene nanoflakes (30 nm) as measured by electrochemical impedance sensing and optical monitoring of treated cells was consistent with the biological assay results. Cell-based electrochemical impedance biosensing can be used to assess the toxicity of nanomaterials with different biomedical and environmental applications. © 2013 Wiley Periodicals, Inc.

Prevalence of patient-reported gastrointestinal symptoms and agreement with clinician toxicity assessments in radiation therapy for anal cancer.

PubMed

Tom, Ashlyn; Bennett, Antonia V; Rothenstein, Diana; Law, Ethel; Goodman, Karyn A

2018-01-01

Gastrointestinal (GI) symptoms pose a significant burden to patients receiving chemoradiation therapy (CRT) for anal cancer; however, the impact of symptoms from the patient perspective has not been quantified. This retrospective study examined and compared patient and clinician reports of acute GI toxicity during CRT. Patients treated with definitive RT using intensity-modulated radiation therapy for anal cancer between 9/09 and 11/12 were reviewed. Median RT dose was 56 Gy (range 45-56), and 76 patients (97%) received concurrent 5-fluorouracil-based chemotherapy. During RT, patients completed the 7-item Bowel Problem Scale (BPS) weekly. Clinicians assessed toxicity separately using CTCAE v. 3.0. Scores of BPS ≥ 3 and CTCAE ≥ 1 were considered to be clinically meaningful. Agreement of the two assessments was evaluated by Cohen's kappa coefficient. Seventy-eight patients completed at least one BPS and had a corresponding clinician assessment. Patients reporting scores of ≥3 was highest at week 5 (n = 68) for diarrhea (44.1%), proctitis (57.4%), and mucus (48.4%), while urgency (47.6%), tenesmus (31.7%), and cramping (27%) were highest at week 4 (n = 63). Baseline bleeding scores (26.7%; score ≥3) improved during treatment (13.4% at week 5). "Poor" agreement was observed between patient- and clinician-reported proctitis (Cohen's k = 0.11; n = 58); however, there was "good" agreement for diarrhea (Cohen's k = 0.68; n = 58). Acute GI toxicity during definitive CRT for anal cancer was most significant during weeks 4-5, while rectal bleeding improved during treatment. Discrepancies in patient- and clinician-reported symptoms demonstrate the potential for patient-reported outcomes to be useful tools for anal cancer clinical assessments.

Comparative toxicity of two azadirachtin-based neem pesticides to Daphnia pulex.

PubMed

Goktepe, Ipek; Plhak, Leslie C

2002-01-01

Azadirachtin (AZA)-based pesticides (Neemix and Bioneem) demonstrated toxicity in 48-h nonrenewal toxicity assays using Daphnia pulex at levels that were comparable with several organophosphate pesticides. The median lethal concentration (LC50) values for the two neem pesticides were found to be 0.028 and 0.033 microl/ml, respectively. The LC50 value for nonformulated (95% pure) AZA was determined to be 0.382 microg AZA/ml. Neemix and Bioneem were exposed to air and northern sky daylight in a light box at 24 and 37 degrees C for 1, 3, 6, and 9 d. Standard 48-h acute toxicity tests were used to determine the effect of aging in these dry environmental conditions. Neemix and Bioneem were also fractionated into volatile and nonvolatile fractions, and the toxicity of each was tested. Compared with Neemix, Bioneem remained toxic longer when exposed to light and air at 37 degrees C, indicating that this pesticide may be less prone to environmental degradation. When fractionated, the nonvolatile fractions for both pesticides exhibited significantly lower LC50 values than the full formulations. These results suggest that, depending on the application rate and environmental fate, AZA-based pesticides may have direct adverse effects on aquatic organisms and that the toxicity and stability of formulated pesticides depend on factors other than only the AZA concentration.

Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies

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

Salama, Joseph K.; Mundt, Arno J.; Department of Radiation Oncology, University of Illinois, Chicago, IL

2006-07-15

Purpose: The aim of this article is to report a preliminary analysis of our initial clinical experience with extended-field intensity-modulated radiotherapy for gynecologic malignancies. Methods and Materials: Between November 2002 and May 2005, 13 women with gynecologic malignancies were treated with extended-field radiation therapy. Of the women, 7 had endometrial cancer, 4 cervical cancer, 1 recurrent endometrial cancer, and 1 suspected cervical cancer. All women underwent computed tomography planning, with the upper vagina, parametria, and uterus (if present) contoured within the CTV. In addition, the clinical target volume contained the pelvic and presacral lymph nodes as well as the para-aorticmore » lymph nodes. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE v 3.0). All late toxicity was scored using the Radiation Therapy Oncology Group late toxicity score. Results: The median follow-up was 11 months. Extended-field intensity-modulated radiation therapy (IMRT) for gynecologic malignancies was well tolerated. Two patients experienced Grade 3 or higher toxicity. Both patients were treated with concurrent cisplatin based chemotherapy. Neither patient was planned with bone marrow sparing. Eleven patients had no evidence of late toxicity. One patient with multiple previous surgeries experienced a bowel obstruction. One patient with bilateral grossly involved and unresectable common iliac nodes experienced bilateral lymphedema. Extended-field-IMRT achieved good local control with only 1 patient, who was metastatic at presentation, and 1 patient not able to complete treatment, experiencing in-field failure. Conclusions: Extended-field IMRT is safe and effective with a low incidence of acute toxicity. Longer follow-up is needed to assess chronic toxicity, although early results are promising.« less

Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement

PubMed Central

Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

2012-01-01

Objectives: Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). Materials and Methods: In vivo toxicity studies were performed in male balb ‘C’ mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. Results: No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. Conclusion: The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement. PMID:23087514

Fish embryo toxicity of carbamazepine, diclofenac and metoprolol.

PubMed

van den Brandhof, Evert-Jan; Montforts, Mark

2010-11-01

Frequently measured pharmaceuticals in environmental samples were tested in fish embryo toxicity (FET) tests with Danio rerio, based on the draft OECD test protocol. In this FET test 2-h-old zebrafish embryos were exposed for 72 h to carbamazepine, diclofenac and metoprolol to observe effects on embryo mortality, gastrulation, somite formation, tail movement and detachment, pigmentation, heartbeat, malformation of head, otoliths and heart, scoliosis, deformity of yolk, and hatching success at 24, 48 and 72 h. We found specific effects on growth retardation above 30.6 mg/l for carbamazepine, on hatching, yolk sac and tail deformation above 1.5mg/l for diclofenac, and on scoliosis and growth retardation above 12.6 mg/l for metoprolol. Scoring all effect parameters, the 72-h-EC(50) values were: for carbamazepine 86.5mg/l, for diclofenac 5.3mg/l and for metoprolol 31.0mg/l (mean measured concentrations). In conclusion, our results for carbamazepine and metoprolol are in agreement with other findings for aquatic toxicity, and also fish embryos responded in much the same way as rat embryos did. For diclofenac, the FET test performs comparably to Early Life Stage testing. Copyright © 2010 Elsevier Inc. All rights reserved.

Mixture toxicity of wood preservative products in the fish embryo toxicity test.

PubMed

Coors, Anja; Dobrick, Jan; Möder, Monika; Kehrer, Anja

2012-06-01

Wood preservative products are used globally to protect wood from fungal decay and insects. We investigated the aquatic toxicity of five commercial wood preservative products, the biocidal active substances and some formulation additives contained therein, as well as six generic binary mixtures of the active substances in the fish embryo toxicity test (FET). Median lethal concentrations (LC50) of the single substances, the mixtures, and the products were estimated from concentration-response curves and corrected for concentrations measured in the test medium. The comparison of the experimentally observed mixture toxicity with the toxicity predicted by the concept of concentration addition (CA) showed less than twofold deviation for all binary mixtures of the active substances and for three of the biocidal products. A more than 60-fold underestimation of the toxicity of the fourth product by the CA prediction was detected and could be explained fully by the toxicity of one formulation additive, which had been labeled as a hazardous substance. The reason for the 4.6-fold underestimation of toxicity of the fifth product could not be explained unambiguously. Overall, the FET was found to be a suitable screening tool to verify whether the toxicity of formulated wood preservatives can reliably be predicted by CA. Applied as a quick and simple nonanimal screening test, the FET may support approaches of applying component-based mixture toxicity predictions within the environmental risk assessment of biocidal products, which is required according to European regulations. Copyright © 2012 SETAC.

Temporal Lobe Toxicity Analysis After Proton Radiation Therapy for Skull Base Tumors

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

Pehlivan, Berrin; Ares, Carmen, E-mail: carmen.ares@psi.ch; Lomax, Antony J.

2012-08-01

Purpose: Temporal lobe (TL) parenchyma toxicity constitutes one of the most frequent late adverse event in high-dose proton therapy (PT) for tumors of the skull base. We analyzed clinical events with dosimetric parameters in our patients treated for skull base tumors with spot-scanning PT. Methods and Materials: Between 1998 and 2005, a total of 62 patients received PT to a median dose of 71.7 Gy (relative biologic effectiveness [RBE]) (range, 63-74 Gy). The dose-volume histogram of each TL and the entire brain parenchyma (BP) were analyzed according to maximum, mean, and minimum dose as well as doses to 0.5, 1,more » 2, and 3 cc of brain volume (D{sub 0.5}, D{sub 1}, D{sub 2}, D{sub 3}) and correlated with clinical events. Generalized equivalent uniform dose (gEUD) values were calculated. Results: At a mean follow-up of 38 months (range, 14-92 months), 2 patients had developed symptomatic Grade 3 and 5 patients asymptomatic Grade 1 TL toxicity. Mean doses to a 2-cc volume of BP increased from 71 {+-} 5 Gy (RBE) for no toxicity to 74 {+-} 5 Gy (RBE) for Grade 1 and to 76 {+-} 2 Gy (RBE) for Grade 3 toxicity. TL events occurred in 6 of 7 patients (86%) at or above dose levels of {>=}64 Gy (RBE) D{sub 3}, {>=}68 Gy (RBE) D{sub 2}, {>=}72 Gy (RBE) D{sub 1}, and {>=}73 Gy (RBE) D{sub 0.5}, respectively (p = NS). No statistically significant dose/volume threshold was detected between patients experiencing no toxicity vs. Grade 1 or Grade 3. A strong trend for Grade 1 and 3 events was observed, when the gEUD was 60 Gy. Conclusions: A statistically significant normal tissue threshold dose for BP has not been successfully defined. However, our data suggest that tolerance of TL and BP to fractionated radiotherapy appears to be correlated with tissue volume included in high-dose regions. Additional follow-up time and patient accrual is likely needed to achieve clinical significance for these dose-volume parameters investigated. Our findings support the importance of

Performance of machine-learning scoring functions in structure-based virtual screening.

PubMed

Wójcikowski, Maciej; Ballester, Pedro J; Siedlecki, Pawel

2017-04-25

Classical scoring functions have reached a plateau in their performance in virtual screening and binding affinity prediction. Recently, machine-learning scoring functions trained on protein-ligand complexes have shown great promise in small tailored studies. They have also raised controversy, specifically concerning model overfitting and applicability to novel targets. Here we provide a new ready-to-use scoring function (RF-Score-VS) trained on 15 426 active and 893 897 inactive molecules docked to a set of 102 targets. We use the full DUD-E data sets along with three docking tools, five classical and three machine-learning scoring functions for model building and performance assessment. Our results show RF-Score-VS can substantially improve virtual screening performance: RF-Score-VS top 1% provides 55.6% hit rate, whereas that of Vina only 16.2% (for smaller percent the difference is even more encouraging: RF-Score-VS top 0.1% achieves 88.6% hit rate for 27.5% using Vina). In addition, RF-Score-VS provides much better prediction of measured binding affinity than Vina (Pearson correlation of 0.56 and -0.18, respectively). Lastly, we test RF-Score-VS on an independent test set from the DEKOIS benchmark and observed comparable results. We provide full data sets to facilitate further research in this area (http://github.com/oddt/rfscorevs) as well as ready-to-use RF-Score-VS (http://github.com/oddt/rfscorevs_binary).

Performance of machine-learning scoring functions in structure-based virtual screening

PubMed Central

Wójcikowski, Maciej; Ballester, Pedro J.; Siedlecki, Pawel

2017-01-01

Classical scoring functions have reached a plateau in their performance in virtual screening and binding affinity prediction. Recently, machine-learning scoring functions trained on protein-ligand complexes have shown great promise in small tailored studies. They have also raised controversy, specifically concerning model overfitting and applicability to novel targets. Here we provide a new ready-to-use scoring function (RF-Score-VS) trained on 15 426 active and 893 897 inactive molecules docked to a set of 102 targets. We use the full DUD-E data sets along with three docking tools, five classical and three machine-learning scoring functions for model building and performance assessment. Our results show RF-Score-VS can substantially improve virtual screening performance: RF-Score-VS top 1% provides 55.6% hit rate, whereas that of Vina only 16.2% (for smaller percent the difference is even more encouraging: RF-Score-VS top 0.1% achieves 88.6% hit rate for 27.5% using Vina). In addition, RF-Score-VS provides much better prediction of measured binding affinity than Vina (Pearson correlation of 0.56 and −0.18, respectively). Lastly, we test RF-Score-VS on an independent test set from the DEKOIS benchmark and observed comparable results. We provide full data sets to facilitate further research in this area (http://github.com/oddt/rfscorevs) as well as ready-to-use RF-Score-VS (http://github.com/oddt/rfscorevs_binary). PMID:28440302

Metal-Polycyclic Aromatic Hydrocarbon Mixture Toxicity in Hyalella azteca. 1. Response Surfaces and Isoboles To Measure Non-additive Mixture Toxicity and Ecological Risk.

PubMed

Gauthier, Patrick T; Norwood, Warren P; Prepas, Ellie E; Pyle, Greg G

2015-10-06

Mixtures of metals and polycyclic aromatic hydrocarbons (PAHs) occur ubiquitously in aquatic environments, yet relatively little is known regarding their potential to produce non-additive toxicity (i.e., antagonism or potentiation). A review of the lethality of metal-PAH mixtures in aquatic biota revealed that more-than-additive lethality is as common as strictly additive effects. Approaches to ecological risk assessment do not consider non-additive toxicity of metal-PAH mixtures. Forty-eight-hour water-only binary mixture toxicity experiments were conducted to determine the additive toxic nature of mixtures of Cu, Cd, V, or Ni with phenanthrene (PHE) or phenanthrenequinone (PHQ) using the aquatic amphipod Hyalella azteca. In cases where more-than-additive toxicity was observed, we calculated the possible mortality rates at Canada's environmental water quality guideline concentrations. We used a three-dimensional response surface isobole model-based approach to compare the observed co-toxicity in juvenile amphipods to predicted outcomes based on concentration addition or effects addition mixtures models. More-than-additive lethality was observed for all Cu-PHE, Cu-PHQ, and several Cd-PHE, Cd-PHQ, and Ni-PHE mixtures. Our analysis predicts Cu-PHE, Cu-PHQ, Cd-PHE, and Cd-PHQ mixtures at the Canadian Water Quality Guideline concentrations would produce 7.5%, 3.7%, 4.4% and 1.4% mortality, respectively.

Developing points-based risk-scoring systems in the presence of competing risks.

PubMed

Austin, Peter C; Lee, Douglas S; D'Agostino, Ralph B; Fine, Jason P

2016-09-30

Predicting the occurrence of an adverse event over time is an important issue in clinical medicine. Clinical prediction models and associated points-based risk-scoring systems are popular statistical methods for summarizing the relationship between a multivariable set of patient risk factors and the risk of the occurrence of an adverse event. Points-based risk-scoring systems are popular amongst physicians as they permit a rapid assessment of patient risk without the use of computers or other electronic devices. The use of such points-based risk-scoring systems facilitates evidence-based clinical decision making. There is a growing interest in cause-specific mortality and in non-fatal outcomes. However, when considering these types of outcomes, one must account for competing risks whose occurrence precludes the occurrence of the event of interest. We describe how points-based risk-scoring systems can be developed in the presence of competing events. We illustrate the application of these methods by developing risk-scoring systems for predicting cardiovascular mortality in patients hospitalized with acute myocardial infarction. Code in the R statistical programming language is provided for the implementation of the described methods. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Observational scores of dampness and mold associated with measurements of microbial agents and moisture in three public schools

PubMed Central

Cho, S. J.; Cox-Ganser, J. M.; Park, J.-H.

2015-01-01

We examined associations between observational dampness scores and measurements of microbial agents and moisture in three public schools. A dampness score was created for each room from 4-point-scale scores (0–3) of water damage, water stains, visible mold, moldy odor, and wetness for each of 8 room components (ceiling, walls, windows, floor, ventilation, furniture, floor trench, and pipes), when present. We created mixed microbial exposure indices (MMEIs) for each of 121 rooms by summing decile ranks of 8 analytes (total culturable fungi; total, Gram-negative, and Gram-positive culturable bacteria; ergosterol; (1→3)-β-D-glucan; muramic acid; and endotoxin) in floor dust. We found significant (P ≤ 0.01) linear associations between the dampness score and culturable bacteria (total, Gram-positive, and Gram-negative) and the MMEIs. Rooms with dampness scores greater than 0.25 (median) had significantly (P < 0.05) higher levels of most microbial agents, MMEIs, and relative moisture content than those with lower scores (≤0.25). Rooms with reported recent water leaks had significantly (P < 0.05) higher dampness scores than those with historical or no reported water leaks. This study suggests that observational assessment of dampness and mold using a standardized form may be valuable for identifying and documenting water damage and associated microbial contamination. PMID:25650175

Albendazole Induced Recurrent Acute Toxic Hepatitis: A Case Report.

PubMed

Bilgic, Yilmaz; Yilmaz, Cengiz; Cagin, Yasir Furkan; Atayan, Yahya; Karadag, Nese; Harputluoglu, Murat Muhsin Muhip

2017-01-01

Drug induced acute toxic hepatitis can be idiosyncratic. Albendazole, a widely used broad spectrum antiparasitic drug is generally accepted as a safe drug. It may cause asymptomatic transient liver enzyme abnormalities but acute toxic hepatitis is very rare. Case Report : Herein, we present the case of 47 year old woman with recurrent acute toxic hepatitis after a single intake of albendazole in 2010 and 2014. The patient was presented with symptoms and findings of anorexia, vomiting and jaundice. For diagnosis, other acute hepatitis etiologies were excluded. Roussel Uclaf Causality Assessment Method (RUCAM) score was calculated and found to be 10, which meant highly probable drug hepatotoxicity. Within 2 months, all pathological findings came to normal. There are a few reported cases of albendazole induced toxic hepatitis, but at adults, there is no known recurrent acute toxic hepatitis due to albendazole at this certainty according to RUCAM score. Physicians should be aware of this rare and potentially fatal adverse effect of albendazole. © Acta Gastro-Enterologica Belgica.

Prognostic score–based balance measures for propensity score methods in comparative effectiveness research

PubMed Central

Stuart, Elizabeth A.; Lee, Brian K.; Leacy, Finbarr P.

2013-01-01

Objective Examining covariate balance is the prescribed method for determining when propensity score methods are successful at reducing bias. This study assessed the performance of various balance measures, including a proposed balance measure based on the prognostic score (also known as the disease-risk score), to determine which balance measures best correlate with bias in the treatment effect estimate. Study Design and Setting The correlations of multiple common balance measures with bias in the treatment effect estimate produced by weighting by the odds, subclassification on the propensity score, and full matching on the propensity score were calculated. Simulated data were used, based on realistic data settings. Settings included both continuous and binary covariates and continuous covariates only. Results The standardized mean difference in prognostic scores, the mean standardized mean difference, and the mean t-statistic all had high correlations with bias in the effect estimate. Overall, prognostic scores displayed the highest correlations of all the balance measures considered. Prognostic score measure performance was generally not affected by model misspecification and performed well under a variety of scenarios. Conclusion Researchers should consider using prognostic score–based balance measures for assessing the performance of propensity score methods for reducing bias in non-experimental studies. PMID:23849158

"Score the Core" Web-based pathologist training tool improves the accuracy of breast cancer IHC4 scoring.

PubMed

Engelberg, Jesse A; Retallack, Hanna; Balassanian, Ronald; Dowsett, Mitchell; Zabaglo, Lila; Ram, Arishneel A; Apple, Sophia K; Bishop, John W; Borowsky, Alexander D; Carpenter, Philip M; Chen, Yunn-Yi; Datnow, Brian; Elson, Sarah; Hasteh, Farnaz; Lin, Fritz; Moatamed, Neda A; Zhang, Yanhong; Cardiff, Robert D

2015-11-01

Hormone receptor status is an integral component of decision-making in breast cancer management. IHC4 score is an algorithm that combines hormone receptor, HER2, and Ki-67 status to provide a semiquantitative prognostic score for breast cancer. High accuracy and low interobserver variance are important to ensure the score is accurately calculated; however, few previous efforts have been made to measure or decrease interobserver variance. We developed a Web-based training tool, called "Score the Core" (STC) using tissue microarrays to train pathologists to visually score estrogen receptor (using the 300-point H score), progesterone receptor (percent positive), and Ki-67 (percent positive). STC used a reference score calculated from a reproducible manual counting method. Pathologists in the Athena Breast Health Network and pathology residents at associated institutions completed the exercise. By using STC, pathologists improved their estrogen receptor H score and progesterone receptor and Ki-67 proportion assessment and demonstrated a good correlation between pathologist and reference scores. In addition, we collected information about pathologist performance that allowed us to compare individual pathologists and measures of agreement. Pathologists' assessment of the proportion of positive cells was closer to the reference than their assessment of the relative intensity of positive cells. Careful training and assessment should be used to ensure the accuracy of breast biomarkers. This is particularly important as breast cancer diagnostics become increasingly quantitative and reproducible. Our training tool is a novel approach for pathologist training that can serve as an important component of ongoing quality assessment and can improve the accuracy of breast cancer prognostic biomarkers. Copyright © 2015 Elsevier Inc. All rights reserved.

Adapted Finnegan scoring list for observation of anti-depressant exposed infants.

PubMed

Kieviet, Noera; van Ravenhorst, Mariëtte; Dolman, Koert M; van de Ven, Peter M; Heres, Marion; Wennink, Hanneke; Honig, Adriaan

2015-01-01

The Finnegan scoring list (FSL) is widely used to screen for poor neonatal adaptation in infants exposed to anti-depressants in utero. However, the large number of FSL-items and differential weighing of each item is time consuming. The aim of this study was to shorten and simplify the FSL yet preserving its clinimetric properties. This observational study examined infants exposed to an anti-depressant during pregnancy admitted for at least 72 h on a maternity ward. Trained nurses completed the FSL three times daily. Items for the adapted FSL were selected through forward analysis whereby the number of selected items was based on the area under the curve (AUC). Internal validity was assessed by cross-validation. 183 infants met the inclusion criteria. By forward analysis eight equally-weighed items resulted in an AUC of 0.91. In cross-validation, the mean AUC was 0.89 for 8 items. This adapted FSL had a sensitivity of 97.7% and specificity of 37.0% and a sensitivity of 41.9% and specificity of 86.2% regarding a cut-off of, respectively, 1 and 2. An adapted FSL with eight equally-weighed items has acceptable clinimetric properties and can serve as an easy to apply screening tool in infants exposed to anti-depressants during pregnancy.

Chronic arsenic intoxication diagnostic score (CAsIDS).

PubMed

Dani, Sergio Ulhoa; Walter, Gerhard Franz

2018-01-01

Arsenic and its compounds are well-established, potent, environmentally widespread and persistent toxicants with metabolic, genotoxic, mutagenic, teratogenic, epigenetic and carcinogenic effects. Arsenic occurs naturally in the Earth's crust, but anthropogenic arsenic emissions have surmounted the emissions from important natural sources such as volcanism. Inorganic arsenicals exhibit acute and chronic toxicities in virtually all cell types and tissues, and hence arsenic intoxication affects multiple systems. Whereas acute arsenic intoxication is rare and relatively easy to diagnose, chronic arsenic intoxication (CAsI) is common but goes often misdiagnosed. Based on a review of the literature as well as our own clinical experience, we propose a chronic arsenic intoxication diagnostic score (CAsIDS). A distinctive feature of CAsIDS is the use of bone arsenic load as an essential criterion for the individual risk assessment of chronic arsenic intoxication, combined with a systemic clinical assessment. We present clinical examples where CAsIDS is applied for the diagnosis of CAsI, review the main topics of the toxicity of arsenic in different cell and organ systems and discuss the therapy and prevention of disease caused or aggravated by chronic arsenic intoxication. CAsIDS can help physicians establish the diagnosis of CAsI and associated conditions. Copyright © 2017 John Wiley & Sons, Ltd.

Cell-based Assays for Assessing Toxicity: A Basic Guide.

PubMed

Parboosing, Raveen; Mzobe, Gugulethu; Chonco, Louis; Moodley, Indres

2016-01-01

Assessment of toxicity is an important component of the drug discovery process. Cellbased assays are a popular choice for assessing cytotoxicity. However, these assays are complex because of the wide variety of formats and methods that are available, lack of standardization, confusing terminology and the inherent variability of biological systems and measurement. This review is intended as a guide on how to take these factors into account when planning, conducting and/or interpreting cell based toxicity assays. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Web-based scoring of the dicentric assay, a collaborative biodosimetric scoring strategy for population triage in large scale radiation accidents.

PubMed

Romm, H; Ainsbury, E; Bajinskis, A; Barnard, S; Barquinero, J F; Barrios, L; Beinke, C; Puig-Casanovas, R; Deperas-Kaminska, M; Gregoire, E; Oestreicher, U; Lindholm, C; Moquet, J; Rothkamm, K; Sommer, S; Thierens, H; Vral, A; Vandersickel, V; Wojcik, A

2014-05-01

In the case of a large scale radiation accident high throughput methods of biological dosimetry for population triage are needed to identify individuals requiring clinical treatment. The dicentric assay performed in web-based scoring mode may be a very suitable technique. Within the MULTIBIODOSE EU FP7 project a network is being established of 8 laboratories with expertise in dose estimations based on the dicentric assay. Here, the manual dicentric assay was tested in a web-based scoring mode. More than 23,000 high resolution images of metaphase spreads (only first mitosis) were captured by four laboratories and established as image galleries on the internet (cloud). The galleries included images of a complete dose effect curve (0-5.0 Gy) and three types of irradiation scenarios simulating acute whole body, partial body and protracted exposure. The blood samples had been irradiated in vitro with gamma rays at the University of Ghent, Belgium. Two laboratories provided image galleries from Fluorescence plus Giemsa stained slides (3 h colcemid) and the image galleries from the other two laboratories contained images from Giemsa stained preparations (24 h colcemid). Each of the 8 participating laboratories analysed 3 dose points of the dose effect curve (scoring 100 cells for each point) and 3 unknown dose points (50 cells) for each of the 3 simulated irradiation scenarios. At first all analyses were performed in a QuickScan Mode without scoring individual chromosomes, followed by conventional scoring (only complete cells, 46 centromeres). The calibration curves obtained using these two scoring methods were very similar, with no significant difference in the linear-quadratic curve coefficients. Analysis of variance showed a significant effect of dose on the yield of dicentrics, but no significant effect of the laboratories, different methods of slide preparation or different incubation times used for colcemid. The results obtained to date within the MULTIBIODOSE

Comparison of the Classifier Oriented Gait Score and the Gait Profile Score based on imitated gait impairments.

PubMed

Christian, Josef; Kröll, Josef; Schwameder, Hermann

2017-06-01

Common summary measures of gait quality such as the Gait Profile Score (GPS) are based on the principle of measuring a distance from the mean pattern of a healthy reference group in a gait pattern vector space. The recently introduced Classifier Oriented Gait Score (COGS) is a pathology specific score that measures this distance in a unique direction, which is indicated by a linear classifier. This approach has potentially improved the discriminatory power to detect subtle changes in gait patterns but does not incorporate a profile of interpretable sub-scores like the GPS. The main aims of this study were to extend the COGS by decomposing it into interpretable sub-scores as realized in the GPS and to compare the discriminative power of the GPS and COGS. Two types of gait impairments were imitated to enable a high level of control of the gait patterns. Imitated impairments were realized by restricting knee extension and inducing leg length discrepancy. The results showed increased discriminatory power of the COGS for differentiating diverse levels of impairment. Comparison of the GPS and COGS sub-scores and their ability to indicate changes in specific variables supports the validity of both scores. The COGS is an overall measure of gait quality with increased power to detect subtle changes in gait patterns and might be well suited for tracing the effect of a therapeutic treatment over time. The newly introduced sub-scores improved the interpretability of the COGS, which is helpful for practical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

From Perception to Practice: The Impact of Teachers' Scoring Experience on Performance-based Instruction and Classroom Assessment

ERIC Educational Resources Information Center

Goldberg, Gail Lynn; Roswell, Barbara Sherr

2000-01-01

Studied the impact of experience scoring the Maryland School Performance Assessment tasks on teachers' instructional and classroom assessment practice. Interview data, questionnaires, classroom observation, and classroom artifacts from approximately 5 teacher-scorers demonstrated that teachers' appropriation of performance-based instruction may be…

College Math Assessment: SAT Scores vs. College Math Placement Scores

ERIC Educational Resources Information Center

Foley-Peres, Kathleen; Poirier, Dawn

2008-01-01

Many colleges and university's use SAT math scores or math placement tests to place students in the appropriate math course. This study compares the use of math placement scores and SAT scores for 188 freshman students. The student's grades and faculty observations were analyzed to determine if the SAT scores and/or college math assessment scores…

Is ozonation environmentally benign for reverse osmosis concentrate treatment? Four-level analysis on toxicity reduction based on organic matter fractionation.

PubMed

Weng, Jingxia; Jia, Huichao; Wu, Bing; Pan, Bingcai

2018-01-01

Ozonation is a promising option to treat reverse osmosis concentrate (ROC). However, a systematic understanding and assessment of ozonation on toxicity reduction is insufficient. In this study, ROC sampled from a typical industrial park wastewater treatment plant of China was fractionated into hydrophobic acid (HOA), hydrophobic base (HOB), hydrophobic neutral (HON), and hydrophilic fraction (HI). Systematic bioassays covering bacteria, algae, fish, and human cell lines were conducted to reveal the role of ozonation in toxicity variation of the four ROC fractions. HOA in the raw ROC exhibited the highest toxicity, followed by HON and HI. Ozonation significantly reduced total organic carbon (TOC) and UV 254 values in HOA, HON, and HI and their toxicity except in HOB. Correlation analysis indicated that chemical data (TOC and UV 254 ) of HOA and HON correlated well with their toxicities; however, poor correlations were observed for HOB and HI, suggesting that a battery of toxicity assays is necessary. This study indicates that TOC reduction during ozonation could not fully reflect the toxicity issue, and toxicity assessment is required in conjunction with the chemical data to evaluate the effectiveness of ozonation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of clinically discriminating, evidence-based checklist items on the reliability of scores from an Internal Medicine residency OSCE.

PubMed

Daniels, Vijay J; Bordage, Georges; Gierl, Mark J; Yudkowsky, Rachel

2014-10-01

Objective structured clinical examinations (OSCEs) are used worldwide for summative examinations but often lack acceptable reliability. Research has shown that reliability of scores increases if OSCE checklists for medical students include only clinically relevant items. Also, checklists are often missing evidence-based items that high-achieving learners are more likely to use. The purpose of this study was to determine if limiting checklist items to clinically discriminating items and/or adding missing evidence-based items improved score reliability in an Internal Medicine residency OSCE. Six internists reviewed the traditional checklists of four OSCE stations classifying items as clinically discriminating or non-discriminating. Two independent reviewers augmented checklists with missing evidence-based items. We used generalizability theory to calculate overall reliability of faculty observer checklist scores from 45 first and second-year residents and predict how many 10-item stations would be required to reach a Phi coefficient of 0.8. Removing clinically non-discriminating items from the traditional checklist did not affect the number of stations (15) required to reach a Phi of 0.8 with 10 items. Focusing the checklist on only evidence-based clinically discriminating items increased test score reliability, needing 11 stations instead of 15 to reach 0.8; adding missing evidence-based clinically discriminating items to the traditional checklist modestly improved reliability (needing 14 instead of 15 stations). Checklists composed of evidence-based clinically discriminating items improved the reliability of checklist scores and reduced the number of stations needed for acceptable reliability. Educators should give preference to evidence-based items over non-evidence-based items when developing OSCE checklists.

Precision analysis of a quantitative CT liver surface nodularity score.

PubMed

Smith, Andrew; Varney, Elliot; Zand, Kevin; Lewis, Tara; Sirous, Reza; York, James; Florez, Edward; Abou Elkassem, Asser; Howard-Claudio, Candace M; Roda, Manohar; Parker, Ellen; Scortegagna, Eduardo; Joyner, David; Sandlin, David; Newsome, Ashley; Brewster, Parker; Lirette, Seth T; Griswold, Michael

2018-04-26

To evaluate precision of a software-based liver surface nodularity (LSN) score derived from CT images. An anthropomorphic CT phantom was constructed with simulated liver containing smooth and nodular segments at the surface and simulated visceral and subcutaneous fat components. The phantom was scanned multiple times on a single CT scanner with adjustment of image acquisition and reconstruction parameters (N = 34) and on 22 different CT scanners from 4 manufacturers at 12 imaging centers. LSN scores were obtained using a software-based method. Repeatability and reproducibility were evaluated by intraclass correlation (ICC) and coefficient of variation. Using abdominal CT images from 68 patients with various stages of chronic liver disease, inter-observer agreement and test-retest repeatability among 12 readers assessing LSN by software- vs. visual-based scoring methods were evaluated by ICC. There was excellent repeatability of LSN scores (ICC:0.79-0.99) using the CT phantom and routine image acquisition and reconstruction parameters (kVp 100-140, mA 200-400, and auto-mA, section thickness 1.25-5.0 mm, field of view 35-50 cm, and smooth or standard kernels). There was excellent reproducibility (smooth ICC: 0.97; 95% CI 0.95, 0.99; CV: 7%; nodular ICC: 0.94; 95% CI 0.89, 0.97; CV: 8%) for LSN scores derived from CT images from 22 different scanners. Inter-observer agreement for the software-based LSN scoring method was excellent (ICC: 0.84; 95% CI 0.79, 0.88; CV: 28%) vs. good for the visual-based method (ICC: 0.61; 95% CI 0.51, 0.69; CV: 43%). Test-retest repeatability for the software-based LSN scoring method was excellent (ICC: 0.82; 95% CI 0.79, 0.84; CV: 12%). The software-based LSN score is a quantitative CT imaging biomarker with excellent repeatability, reproducibility, inter-observer agreement, and test-retest repeatability.

Comparison between treatment effects in a randomised controlled trial and an observational study using propensity scores in primary care.

PubMed

Stuart, Beth L; Grebel, Louise En; Butler, Christopher C; Hood, Kerenza; Verheij, Theo J M; Little, Paul

2017-09-01

Although randomised controlled trials (RCTs) are considered 'gold standard' evidence, they are not always feasible or appropriate, and may represent a select population. Observational studies provide a useful alternative to enhance applicability, but results can be biased due to confounding. To explore the utility of propensity scores for causal inference in an observational study. Comparison of the effect of amoxicillin on key outcomes in an international RCT and observational study of lower respiratory tract infections. Propensity scores were calculated and applied as probability weights in the analyses. The adjusted results were compared with the effects reported in the RCT. Groups were well balanced in the RCT but significantly imbalanced in the observational study, with evidence of confounding by indication: patients receiving antibiotics tended to be older and more unwell at baseline consultation. In the trial duration of symptoms (hazard ratio 1.06, 95% CI = 0.96 to 1.18) and symptom severity (-0.07, 95% CI = -0.15 to 0.007) did not differ between groups. Weighting by propensity score in the observational study resulted in very similar estimates of effect: duration of symptoms (hazard ratio 1.06, 95% CI = 0.80 to 1.40) and difference for symptom severity (-0.07, 95% CI = -0.34 to 0.20). The observational study, after conditioning on propensity score, echoed the trial results. Provided that detailed information is available on potential sources of confounding, effects of interventions can probably be assessed reasonably well in observational datasets, allowing them to be more directly compared with the results of RCTs. © British Journal of General Practice 2017.

Toxicity assessment of individual ingredients of synthetic-based drilling muds (SBMs).

PubMed

Bakhtyar, Sajida; Gagnon, Marthe Monique

2012-09-01

Synthetic-based drilling muds (SBMs) offer excellent technical characteristics while providing improved environmental performance over other drilling muds. The low acute toxicity and high biodegradability of SBMs suggest their discharge at sea would cause minimal impacts on marine ecosystems, however, chronic toxicity testing has demonstrated adverse effects of SBMs on fish health. Sparse environmental monitoring data indicate effects of SBMs on bottom invertebrates. However, no environmental toxicity assessment has been performed on fish attracted to the cutting piles. SBM formulations are mostly composed of synthetic base oils, weighting agents, and drilling additives such as emulsifiers, fluid loss agents, wetting agents, and brine. The present study aimed to evaluate the impact of exposure to individual ingredients of SBMs on fish health. To do so, a suite of biomarkers [ethoxyresorufin-O-deethylase (EROD) activity, biliary metabolites, sorbitol dehydrogenase (SDH) activity, DNA damage, and heat shock protein] have been measured in pink snapper (Pagrus auratus) exposed for 21 days to individual ingredients of SBMs. The primary emulsifier (Emul S50) followed by the fluid loss agent (LSL 50) caused the strongest biochemical responses in fish. The synthetic base oil (Rheosyn) caused the least response in juvenile fish. The results suggest that the impact of Syndrill 80:20 on fish health might be reduced by replacement of the primary emulsifier Emul S50 with an alternative ingredient of less toxicity to aquatic biota. The research provides a basis for improving the environmental performance of SBMs by reducing the environmental risk of their discharge and providing environmental managers with information regarding the potential toxicity of individual ingredients.

Improved Cell Sensitivity and Longevity in a Rapid Impedance-based Toxicity Sensor

DTIC Science & Technology

2009-01-06

sensitivity and longevity in a rapid impedance-based toxicity sensor† Improved cell sensitivity and longevityTheresa M. Curtis,a** Joel Tabb,a Lori...Romeo,a Steven J. Schwager,b Mark W. Widderc* and William H. van der Schaliec ABSTRACT: A number of toxicity sensors for testing field water using a...range of eukaryotic cell types have been proposed, but it has been difficult to identify sensors with both appropriate sensitivity to toxicants and the

Observational scores of dampness and mold associated with measurements of microbial agents and moisture in three public schools.

PubMed

Cho, S J; Cox-Ganser, J M; Park, J-H

2016-04-01

We examined associations between observational dampness scores and measurements of microbial agents and moisture in three public schools. A dampness score was created for each room from 4-point-scale scores (0-3) of water damage, water stains, visible mold, moldy odor, and wetness for each of 8 room components (ceiling, walls, windows, floor, ventilation, furniture, floor trench, and pipes), when present. We created mixed microbial exposure indices (MMEIs) for each of 121 rooms by summing decile ranks of 8 analytes (total culturable fungi; total, Gram-negative, and Gram-positive culturable bacteria; ergosterol; (1→3)-β-D-glucan; muramic acid; and endotoxin) in floor dust. We found significant (P ≤ 0.01) linear associations between the dampness score and culturable bacteria (total, Gram-positive, and Gram-negative) and the MMEIs. Rooms with dampness scores greater than 0.25 (median) had significantly (P < 0.05) higher levels of most microbial agents, MMEIs, and relative moisture content than those with lower scores (≤0.25). Rooms with reported recent water leaks had significantly (P < 0.05) higher dampness scores than those with historical or no reported water leaks. This study suggests that observational assessment of dampness and mold using a standardized form may be valuable for identifying and documenting water damage and associated microbial contamination. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Petroleum Hydrocarbon Mixture Toxicity and a Trait Based Approach to Soil Invertebrate Species for Site Specific Risk Assessments.

PubMed

Gainer, Amy; Cousins, Mark; Hogan, Natacha; Siciliano, Steven D

2018-05-05

Although petroleum hydrocarbons (PHCs) released to the environment typically occur as mixtures, PHC remediation guidelines often reflect individual substance toxicity. It is well documented that groups of aliphatic PHCs act via the same mechanism of action, nonpolar narcosis and, theoretically, concentration addition mixture toxicity principles apply. To assess this theory, ten standardized acute and chronic soil invertebrate toxicity tests on a range of organisms (Eisenia fetida, Lumbricus terrestris, Enchytraeus crypticus, Folsomia candida, Oppia nitens and Hypoaspis aculeifer) were conducted with a refined PHC binary mixture. Reference models for concentration addition and independent action were applied to the mixture toxicity data with consideration of synergism, antagonism and dose level toxicity. Both concentration addition and independent action, without further interactions, provided the best fit with observed response to the mixture. Individual fraction effective concentration values were predicted from optimized, fitted reference models. Concentration addition provided a better estimate than independent action of individual fraction effective concentrations based on comparison with available literature and species trends observed in toxic responses to the mixture. Interspecies differences in standardized laboratory soil invertebrate species responses to PHC contaminated soil was reflected in unique traits. Diets that included soil, large body size, permeable cuticle, low lipid content, lack of ability to molt and no maternal transfer were traits linked to a sensitive survival response to PHC contaminated soil in laboratory tests. Traits linked to sensitive reproduction response in organisms tested were long life spans with small clutch sizes. By deriving single fraction toxicity endpoints considerate of mixtures, we reduce resources and time required in conducting site specific risk assessments for the protection of soil organism's exposure pathway. This

An Exploration of Alternative Scoring Methods Using Curriculum-Based Measurement in Early Writing

ERIC Educational Resources Information Center

Allen, Abigail A.; Poch, Apryl L.; Lembke, Erica S.

2018-01-01

This manuscript describes two empirical studies of alternative scoring procedures used with curriculum-based measurement in writing (CBM-W). Study 1 explored the technical adequacy of a trait-based rubric in first grade. Study 2 explored the technical adequacy of a trait-based rubric, production-dependent, and production-independent scores in…

Comparison of toxicity of class-based organic chemicals to algae and fish based on discrimination of excess toxicity from baseline level.

PubMed

Li, Jin J; Tai, Hong W; Yu, Yang; Wen, Yang; Wang, Xiao H; Zhao, Yuan H

2015-07-01

Toxicity data to fish and algae were used to investigate excess toxicity between species. Results show that chemicals exhibiting excess toxicity to fish also show excess toxicity to algae for most of the compounds. This indicates that they share the same mode of action between species. Similar relationships between logKOW and toxicities to fish and algae for baseline and less inert compounds suggest that they have similar critical body residues in the two species. Differences in excess toxicity for some compounds suggest that there is a difference of physiological structure and metabolism between fish and algae. Some reactive compounds (e.g. polyamines) exhibit greater toxic effects for algae than those for fish because of relatively low bio-uptake potential of these hydrophilic compounds in fish as compared with that in algae. Esters exhibiting greater toxicity in fish than that in algae indicate that metabolism can affect the discrimination of excess toxicity from baseline level. Algae growth inhibition is a very good surrogate for fish lethality. This is not only because overall toxicity sensitivity to algae is greater than that to fish, but also the excess toxicity calculated from algal toxicity can better reflect reactivity of compounds with target molecules than fish toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction.

PubMed

Pujol-Vila, F; Vigués, N; Guerrero-Navarro, A; Jiménez, S; Gómez, D; Fernández, M; Bori, J; Vallès, B; Riva, M C; Muñoz-Berbel, X; Mas, J

2016-03-03

Water quality assessment requires a continuous and strict analysis of samples to guarantee compliance with established standards. Nowadays, the increasing number of pollutants and their synergistic effects lead to the development general toxicity bioassays capable to analyse water pollution as a whole. Current general toxicity methods, e.g. Microtox(®), rely on long operation protocols, the use of complex and expensive instrumentation and sample pre-treatment, which should be transported to the laboratory for analysis. These requirements delay sample analysis and hence, the response to avoid an environmental catastrophe. In an attempt to solve it, a fast (15 min) and low-cost toxicity bioassay based on the chromatic changes associated to bacterial ferricyanide reduction is here presented. E. coli cells (used as model bacteria) were stably trapped on low-cost paper matrices (cellulose-based paper discs, PDs) and remained viable for long times (1 month at -20 °C). Apart from bacterial carrier, paper matrices also acted as a fluidic element, allowing fluid management without the need of external pumps. Bioassay evaluation was performed using copper as model toxic agent. Chromatic changes associated to bacterial ferricyanide reduction were determined by three different transduction methods, i.e. (i) optical reflectometry (as reference method), (ii) image analysis and (iii) visual inspection. In all cases, bioassay results (in terms of half maximal effective concentrations, EC50) were in agreement with already reported data, confirming the good performance of the bioassay. The validation of the bioassay was performed by analysis of real samples from natural sources, which were analysed and compared with a reference method (i.e. Microtox). Obtained results showed agreement for about 70% of toxic samples and 80% of non-toxic samples, which may validate the use of this simple and quick protocol in the determination of general toxicity. The minimum instrumentation

A comparison of fecal percent dry matter and number of Cryptosporidium parvum oocysts shed to observational fecal consistency scoring in dairy calves.

PubMed

Bellosa, Mary L; Nydam, Daryl V; Liotta, Janice L; Zambriski, Jennifer A; Linden, Thomas C; Bowman, Dwight D

2011-04-01

Evaluation of dairy calf feces is often used in research and for clinical decision making to assess severity of diarrhea. However, this has not been validated for agreement between dry matter content and observed fecal consistency. Therefore, a comparison of observed fecal consistency score to fecal percent dry matter and Cryptosporidium parvum oocyst shedding was performed to assess the accuracy of observational scoring as a measure of diarrhea and its association with number of oocysts shed. Fecal samples from 20 dairy calves experimentally infected with C. parvum oocysts were collected daily post-infection and scored on a scale from 1 to 4, with 1 being normal feces to 4 being severe diarrhea. An aliquot of each sample was analyzed for percent dry matter and Cryptosporidium oocyst counts by using immunofluorescent microscopy. Fecal consistency scores of 1, 2, 3, and 4 had median percent dry matter of 20.9, 16.3, 9.6, and 5.8, respectively. Using percent dry matter assessed by fecal consistency scoring were significantly different from each other (P < 0.001). A higher fecal consistency score also was associated with a greater number of Cryptosporidium oocysts shed (P < 0 .0001). Scores of 1, 2, 3, and 4 had median oocyst counts of 0, 0, 1.3 × 10⁶, and 2.8 × 10⁶, respectively. These results suggest that observational scoring is a useful proxy to assess diarrhea in dairy calves.

Toxicity of formulants and heavy metals in glyphosate-based herbicides and other pesticides.

PubMed

Defarge, N; Spiroux de Vendômois, J; Séralini, G E

2018-01-01

The major pesticides of the world are glyphosate-based herbicides (GBH), and their toxicity is highly debated. To understand their mode of action, the comparative herbicidal and toxicological effects of glyphosate (G) alone and 14 of its formulations were studied in this work, as a model for pesticides. GBH are mixtures of water, with commonly 36-48% G claimed as the active principle. As with other pesticides, 10-20% of GBH consist of chemical formulants. We previously identified these by mass spectrometry and found them to be mainly families of petroleum-based oxidized molecules, such as POEA, and other contaminants. We exposed plants and human cells to the components of formulations, both mixed and separately, and measured toxicity and human cellular endocrine disruption below the direct toxicity experimentally measured threshold. G was only slightly toxic on plants at the recommended dilutions in agriculture, in contrast with the general belief. In the short term, the strong herbicidal and toxic properties of its formulations were exerted by the POEA formulant family alone. The toxic effects and endocrine disrupting properties of the formulations were mostly due to the formulants and not to G. In this work, we also identified by mass spectrometry the heavy metals arsenic, chromium, cobalt, lead and nickel, which are known to be toxic and endocrine disruptors, as contaminants in 22 pesticides, including 11 G-based ones. This could also explain some of the adverse effects of the pesticides. In in vivo chronic regulatory experiments that are used to establish the acceptable daily intakes of pesticides, G or other declared active ingredients in pesticides are assessed alone, without the formulants. Considering these new data, this assessment method appears insufficient to ensure safety. These results, taken together, shed a new light on the toxicity of these major herbicides and of pesticides in general.

Chemoradiotherapy versus chemotherapy as adjuvant treatment for localized gastric cancer: a propensity score-matched analysis.

PubMed

Girardi, Daniel M; de Lima, Mariana A; Pereira, Gabriel C B; Negrão, Marcelo V; López, Rossana V M; Capareli, Fernanda C; Sabbaga, Jorge; Hoff, Paulo Marcelo G

2018-04-03

Treatment of localized gastric cancer (LGC) consists of surgical resection followed by adjuvant treatment. Both chemoradiation (CRT) and chemotherapy (CT) regimens have shown benefit in survival outcomes versus observation. However, there are few data comparing these approaches. This study included consecutive patients with LGC treated at Instituto do Cancer do Estado de Sao Paulo (ICESP) from 2012 to 2015. CRT was based on the INT-0116 regimen and CT consisted of a platinum and fluoropyrimidine doublet. Treatment choice was based on physician preference. Toxicity was evaluated for every cycle. Overall survival (OS) analysis was performed by Kaplan-Meier. A propensity score-matched analysis was performed to minimize selection bias. A total of 309 patients were evaluated, 227 in CRT group and 82 in CT group. The most prevalent grade 3/4 toxicities in CRT and CT groups were: nausea/vomiting (9.25 vs 4.9%), fatigue (9.3% vs 2.4%), mucositis (4.4% vs 1.2%), neutropenia (37.8% vs 20.9%), febrile neutropenia (3.9% vs 0%), anemia (4.3% vs 6.1%), thrombocytopenia (2.6% vs 4.9%), neuropathy (0 vs 2.4%) and hand-foot syndrome (0.4% vs 2.4%). Two grade 5 toxicities (febrile neutropenia and anemia) occurred in CRT group. There was no difference in the pattern of recurrence. After a median follow-up of 23.5 months (CRT) and 20.6 months (CT), there was no difference in OS between groups. CT and CRT present similar efficacy and tolerability as adjuvant treatment for LGC.

Changes in levels of biomarkers of exposure observed in a controlled study of smokers switched from conventional to reduced toxicant prototype cigarettes.

PubMed

Shepperd, Christopher J; Eldridge, Alison; Camacho, Oscar M; McAdam, Kevin; Proctor, Christopher J; Meyer, Ingo

2013-06-01

Reduced toxicant prototype (RTP) cigarettes with substantially reduced levels of tobacco smoke toxicants have been developed. Evaluation of these prototype cigarettes included measurement of biomarkers of exposure (BoE) to toxicants in smokers switched from conventional cigarettes to the RTPs. A 6-week single-blinded randomised controlled study with occasional clinical confinement was conducted ( ISRCTN7215735). All smoking subjects smoked a conventional cigarette for 2-weeks. Control groups continued to smoke the conventional cigarette while test groups switched to one of three RTP designs. Clinical confinement and additional assessments were performed for all smoking groups after 2 and 4-weeks. A non-smoker group provided background levels of BoE. On average, smokers switched to RTPs with reduced machine yields of toxicants had reduced levels of corresponding BoEs. For vapour phase toxicants such as acrolein and 1,3-butadiene reductions of ⩾70% were observed both in smoke chemistry and BoEs. Reductions in particulate phase toxicants such as tobacco-specific nitrosamines, aromatic amines and polyaromatic hydrocarbons depended upon the technologies used, but were in some cases ⩾80% although some increases in other particulate phase toxicants were observed. However, reductions in BoEs demonstrate that it is possible to produce prototype cigarettes that reduce exposure to toxicants in short-term use. Copyright © 2013 Elsevier Inc. All rights reserved.

Speciation in Metal Toxicity and Metal-Based Therapeutics

PubMed Central

Templeton, Douglas M.

2015-01-01

Metallic elements, ions and compounds produce varying degrees of toxicity in organisms with which they come into contact. Metal speciation is critical to understanding these adverse effects; the adjectives “heavy” and “toxic” are not helpful in describing the biological properties of individual elements, but detailed chemical structures are. As a broad generalization, the metallic form of an element is inert, and the ionic salts are the species that show more significant bioavailability. Yet the salts and other chelates of a metal ion can give rise to quite different toxicities, as exemplified by a range of carcinogenic potential for various nickel species. Another important distinction comes when a metallic element is organified, increasing its lipophilicity and hence its ability to penetrate the blood brain barrier, as is seen, for example, with organic mercury and tin species. Some metallic elements, such as gold and platinum, are themselves useful therapeutic agents in some forms, while other species of the same element can be toxic, thus focusing attention on species interconversions in evaluating metal-based drugs. The therapeutic use of metal-chelating agents introduces new species of the target metal in vivo, and this can affect not only its desired detoxification, but also introduce a potential for further mechanisms of toxicity. Examples of therapeutic iron chelator species are discussed in this context, as well as the more recent aspects of development of chelation therapy for uranium exposure. PMID:29056656

Engineering Student Self-Assessment through Confidence-Based Scoring

ERIC Educational Resources Information Center

Yuen-Reed, Gigi; Reed, Kyle B.

2015-01-01

A vital aspect of an answer is the confidence that goes along with it. Misstating the level of confidence one has in the answer can have devastating outcomes. However, confidence assessment is rarely emphasized during typical engineering education. The confidence-based scoring method described in this study encourages students to both think about…

Classification of Chemicals Based On Structured Toxicity Information

EPA Science Inventory

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-bas...

Pharmacology-based toxicity assessment: towards quantitative risk prediction in humans.

PubMed

Sahota, Tarjinder; Danhof, Meindert; Della Pasqua, Oscar

2016-05-01

Despite ongoing efforts to better understand the mechanisms underlying safety and toxicity, ~30% of the attrition in drug discovery and development is still due to safety concerns. Changes in current practice regarding the assessment of safety and toxicity are required to reduce late stage attrition and enable effective development of novel medicines. This review focuses on the implications of empirical evidence generation for the evaluation of safety and toxicity during drug development. A shift in paradigm is needed to (i) ensure that pharmacological concepts are incorporated into the evaluation of safety and toxicity; (ii) facilitate the integration of historical evidence and thereby the translation of findings across species as well as between in vitro and in vivo experiments and (iii) promote the use of experimental protocols tailored to address specific safety and toxicity questions. Based on historical examples, we highlight the challenges for the early characterisation of the safety profile of a new molecule and discuss how model-based methodologies can be applied for the design and analysis of experimental protocols. Issues relative to the scientific rationale are categorised and presented as a hierarchical tree describing the decision-making process. Focus is given to four different areas, namely, optimisation, translation, analytical construct and decision criteria. From a methodological perspective, the relevance of quantitative methods for estimation and extrapolation of risk from toxicology and safety pharmacology experimental protocols, such as points of departure and potency, is discussed in light of advancements in population and Bayesian modelling techniques (e.g. non-linear mixed effects modelling). Their use in the evaluation of pharmacokinetics (PK) and pharmacokinetic-pharmacodynamic relationships (PKPD) has enabled great insight into the dose rationale for medicines in humans, both in terms of efficacy and adverse events. Comparable benefits

Complex mixture-associated hormesis and toxicity: the case of leather tanning industry.

PubMed

Pagano, Giovanni; Castello, Giuseppe; Gallo, Marialuisa; Borriello, Ilaria; Guida, Marco

2008-01-01

A series of studies investigated the toxicities of tannery-derived complex mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries. Toxicity was evaluated by multiple bioassays including developmental defects and loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus and Sphaerechinus granularis), and algal growth inhibition (Dunaliella tertiolecta and Selenastrum capricornutum). Both VT and ST water extracts resulted in hormetic effects at concentrations ranging 0.1 to 0.3%, and toxicity at levels > or =1%, both in sea urchin embryo and sperm, and in algal growth bioassays. When comparing tannin-based tannery wastewater (TTW) vs. chromium-based tannery effluent (CTE), a hormesis to toxicity trend was observed for TTW both in terms of developmental and fertilization toxicity in sea urchins, and in algal growth inhibition, with hormetic effects at 0.1 to 0.2% TTW, and toxicity at TTW levels > or =1%. Unlike TTW, CTE showed a monotonic toxicity increase from the lowest tested level (0.1%) and CTE toxicity at higher levels was significantly more severe than TTW-induced toxicity. The results support the view that leather production utilizing tannins might be regarded as a more environmentally friendly procedure than chromium-based tanning process.

Accuracy and Efficiency of Recording Pediatric Early Warning Scores Using an Electronic Physiological Surveillance System Compared With Traditional Paper-Based Documentation

PubMed Central

Sefton, Gerri; Lane, Steven; Killen, Roger; Black, Stuart; Lyon, Max; Ampah, Pearl; Sproule, Cathryn; Loren-Gosling, Dominic; Richards, Caitlin; Spinty, Jean; Holloway, Colette; Davies, Coral; Wilson, April; Chean, Chung Shen; Carter, Bernie; Carrol, E.D.

2017-01-01

Pediatric Early Warning Scores are advocated to assist health professionals to identify early signs of serious illness or deterioration in hospitalized children. Scores are derived from the weighting applied to recorded vital signs and clinical observations reflecting deviation from a predetermined “norm.” Higher aggregate scores trigger an escalation in care aimed at preventing critical deterioration. Process errors made while recording these data, including plotting or calculation errors, have the potential to impede the reliability of the score. To test this hypothesis, we conducted a controlled study of documentation using five clinical vignettes. We measured the accuracy of vital sign recording, score calculation, and time taken to complete documentation using a handheld electronic physiological surveillance system, VitalPAC Pediatric, compared with traditional paper-based charts. We explored the user acceptability of both methods using a Web-based survey. Twenty-three staff participated in the controlled study. The electronic physiological surveillance system improved the accuracy of vital sign recording, 98.5% versus 85.6%, P < .02, Pediatric Early Warning Score calculation, 94.6% versus 55.7%, P < .02, and saved time, 68 versus 98 seconds, compared with paper-based documentation, P < .002. Twenty-nine staff completed the Web-based survey. They perceived that the electronic physiological surveillance system offered safety benefits by reducing human error while providing instant visibility of recorded data to the entire clinical team. PMID:27832032

Accuracy and Efficiency of Recording Pediatric Early Warning Scores Using an Electronic Physiological Surveillance System Compared With Traditional Paper-Based Documentation.

PubMed

Sefton, Gerri; Lane, Steven; Killen, Roger; Black, Stuart; Lyon, Max; Ampah, Pearl; Sproule, Cathryn; Loren-Gosling, Dominic; Richards, Caitlin; Spinty, Jean; Holloway, Colette; Davies, Coral; Wilson, April; Chean, Chung Shen; Carter, Bernie; Carrol, E D

2017-05-01

Pediatric Early Warning Scores are advocated to assist health professionals to identify early signs of serious illness or deterioration in hospitalized children. Scores are derived from the weighting applied to recorded vital signs and clinical observations reflecting deviation from a predetermined "norm." Higher aggregate scores trigger an escalation in care aimed at preventing critical deterioration. Process errors made while recording these data, including plotting or calculation errors, have the potential to impede the reliability of the score. To test this hypothesis, we conducted a controlled study of documentation using five clinical vignettes. We measured the accuracy of vital sign recording, score calculation, and time taken to complete documentation using a handheld electronic physiological surveillance system, VitalPAC Pediatric, compared with traditional paper-based charts. We explored the user acceptability of both methods using a Web-based survey. Twenty-three staff participated in the controlled study. The electronic physiological surveillance system improved the accuracy of vital sign recording, 98.5% versus 85.6%, P < .02, Pediatric Early Warning Score calculation, 94.6% versus 55.7%, P < .02, and saved time, 68 versus 98 seconds, compared with paper-based documentation, P < .002. Twenty-nine staff completed the Web-based survey. They perceived that the electronic physiological surveillance system offered safety benefits by reducing human error while providing instant visibility of recorded data to the entire clinical team.

Admission interview scores are associated with clinical performance in an undergraduate physiotherapy course: an observational study.

PubMed

Edgar, Susan; Mercer, Annette; Hamer, Peter

2014-12-01

The purpose of this study was to determine if there is an association between admission interview score and subsequent academic and clinical performance, in a four-year undergraduate physiotherapy course. Retrospective observational study. 141 physiotherapy students enrolled in two entry year groups. Individual student performance in all course units, practical examinations, clinical placements as well as year level and overall Grade Point Average. Predictor variables included admission interview scores, admission academic scores and demographic data (gender, age and entry level). Interview score demonstrated a significant association with performance in three of six clinical placements through the course. This association was stronger than for any other admission criterion although effect sizes were small to moderate. Further, it was the only admission score to have a significant association with overall Clinical Grade Point Average for the two year groups analysed (r=0.322). By contrast, academic scores on entry showed significant associations with all year level Grade Point Averages except Year 4, the clinical year. This is the first study to review the predictive validity of an admission interview for entry into a physiotherapy course in Australia. The results show that performance in this admission interview is associated with overall performance in clinical placements through the course, while academic admission scoring is not. These findings suggest that there is a role for both academic and non-academic selection processes for entry into physiotherapy. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Nursing activities score.

PubMed

Miranda, Dinis Reis; Nap, Raoul; de Rijk, Angelique; Schaufeli, Wilmar; Iapichino, Gaetano

2003-02-01

The instruments used for measuring nursing workload in the intensive care unit (e.g., Therapeutic Intervention Scoring System-28) are based on therapeutic interventions related to severity of illness. Many nursing activities are not necessarily related to severity of illness, and cost-effectiveness studies require the accurate evaluation of nursing activities. The aim of the study was to determine the nursing activities that best describe workload in the intensive care unit and to attribute weights to these activities so that the score describes average time consumption instead of severity of illness. To define by consensus a list of nursing activities, to determine the average time consumption of these activities by use of a 1-wk observational cross-sectional study, and to compare these results with those of the Therapeutic Intervention Scoring System-28. A total of 99 intensive care units in 15 countries. Consecutive admissions to the intensive care units. Daily recording of nursing activities at a patient level and random multimoment recording of these activities. A total of five new items and 14 subitems describing nursing activities in the intensive care unit (e.g., monitoring, care of relatives, administrative tasks) were added to the list of therapeutic interventions in Therapeutic Intervention Scoring System-28. Data from 2,041 patients (6,451 nursing days and 127,951 multimoment recordings) were analyzed. The new activities accounted for 60% of the average nursing time; the new scoring system (Nursing Activities Score) explained 81% of the nursing time (vs. 43% in Therapeutic Intervention Scoring System-28). The weights in the Therapeutic Intervention Scoring System-28 are not derived from the use of nursing time. Our study suggests that the Nursing Activities Score measures the consumption of nursing time in the intensive care unit. These results should be validated in independent databases.

Validity Assessment of Low-risk SCORE Function and SCORE Function Calibrated to the Spanish Population in the FRESCO Cohorts.

PubMed

Baena-Díez, José Miguel; Subirana, Isaac; Ramos, Rafael; Gómez de la Cámara, Agustín; Elosua, Roberto; Vila, Joan; Marín-Ibáñez, Alejandro; Guembe, María Jesús; Rigo, Fernando; Tormo-Díaz, María José; Moreno-Iribas, Conchi; Cabré, Joan Josep; Segura, Antonio; Lapetra, José; Quesada, Miquel; Medrano, María José; González-Diego, Paulino; Frontera, Guillem; Gavrila, Diana; Ardanaz, Eva; Basora, Josep; García, José María; García-Lareo, Manel; Gutiérrez-Fuentes, José Antonio; Mayoral, Eduardo; Sala, Joan; Dégano, Irene R; Francès, Albert; Castell, Conxa; Grau, María; Marrugat, Jaume

2018-04-01

To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women. All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Covariate Balance in Bayesian Propensity Score Approaches for Observational Studies

ERIC Educational Resources Information Center

Chen, Jianshen; Kaplan, David

2015-01-01

Bayesian alternatives to frequentist propensity score approaches have recently been proposed. However, few studies have investigated their covariate balancing properties. This article compares a recently developed two-step Bayesian propensity score approach to the frequentist approach with respect to covariate balance. The effects of different…

Lectin-based food poisoning: a new mechanism of protein toxicity.

PubMed

Miyake, Katsuya; Tanaka, Toru; McNeil, Paul L

2007-08-01

Ingestion of the lectins present in certain improperly cooked vegetables can result in acute GI tract distress, but the mechanism of toxicity is unknown. In vivo, gut epithelial cells are constantly exposed to mechanical and other stresses and consequently individual cells frequently experience plasma membrane disruptions. Repair of these cell surface disruptions allows the wounded cell to survive: failure results in necrotic cell death. Plasma membrane repair is mediated, in part, by an exocytotic event that adds a patch of internal membrane to the defect site. Lectins are known to inhibit exocytosis. We therefore tested the novel hypothesis that lectin toxicity is due to an inhibitory effect on plasma membrane repair. Repair of plasma membrane disruptions and exocytosis of mucus was assessed after treatment of cultured cell models and excised segments of the GI tract with lectins. Plasma membrane disruptions were produced by focal irradiation of individual cells, using a microscope-based laser, or by mechanical abrasion of multiple cells, using a syringe needle. Repair was then assessed by monitoring the cytosolic penetration of dyes incapable of crossing the intact plasma membrane. We found that cell surface-bound lectins potently inhibited plasma membrane repair, and the exocytosis of mucus that normally accompanies the repair response. Lectins potently inhibit plasma membrane repair, and hence are toxic to wounded cells. This represents a novel form of protein-based toxicity, one that, we propose, is the basis of plant lectin food poisoning.

Standard Error of Linear Observed-Score Equating for the NEAT Design with Nonnormally Distributed Data

ERIC Educational Resources Information Center

Zu, Jiyun; Yuan, Ke-Hai

2012-01-01

In the nonequivalent groups with anchor test (NEAT) design, the standard error of linear observed-score equating is commonly estimated by an estimator derived assuming multivariate normality. However, real data are seldom normally distributed, causing this normal estimator to be inconsistent. A general estimator, which does not rely on the…

EFFECT OF NITRATE-BASED BIOREMEDIATION ON CONTAMINANT DISTRIBUTION AND SEDIMENT TOXICITY-COLUMN STUDY

EPA Science Inventory

A laboratory column study was set up to evaluate changes in contaminant distribution and sediment toxicity following nitrate-based bioremediation and to correlate toxicity reduction with loss of fuel components. Glass columns were packed with sediment from an aquifer that had be...

LC-MS based metabolomics and chemometrics study of the toxic effects of copper on Saccharomyces cerevisiae.

PubMed

Farrés, Mireia; Piña, Benjamí; Tauler, Romà

2016-08-01

Copper containing fungicides are used to protect vineyards from fungal infections. Higher residues of copper in grapes at toxic concentrations are potentially toxic and affect the microorganisms living in vineyards, such as Saccharomyces cerevisiae. In this study, the response of the metabolic profiles of S. cerevisiae at different concentrations of copper sulphate (control, 1 mM, 3 mM and 6 mM) was analysed by liquid chromatography coupled to mass spectrometry (LC-MS) and multivariate curve resolution-alternating least squares (MCR-ALS) using an untargeted metabolomics approach. Peak areas of the MCR-ALS resolved elution profiles in control and in Cu(ii)-treated samples were compared using partial least squares regression (PLSR) and PLS-discriminant analysis (PLS-DA), and the intracellular metabolites best contributing to sample discrimination were selected and identified. Fourteen metabolites showed significant concentration changes upon Cu(ii) exposure, following a dose-response effect. The observed changes were consistent with the expected effects of Cu(ii) toxicity, including oxidative stress and DNA damage. This research confirmed that LC-MS based metabolomics coupled to chemometric methods are a powerful approach for discerning metabolomics changes in S. cerevisiae and for elucidating modes of toxicity of environmental stressors, including heavy metals like Cu(ii).

Hyalella IQ Toxicity Test{trademark} as a predictor of whole sediment toxicity with diversely contaminated sediments

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

Douglas, W.S.; Hayes, K.R.

1994-12-31

The IQ TOXICITY TEST{trademark} is a toxicity screening test that evaluates the organism`s galactosidase enzyme system functionality as a predictor of acute toxicity. Organisms are exposed to a potentially toxic solution for approximately one hour. Following the exposure, the organisms are exposed to a slurry of a galactoside sugar tagged with a fluorescent marker (methylumbelliferyl galactoside) for 15--20 minutes. A black light can then be used to examine whether the hemolymph of the organism contains free umbelliferone, which brightly fluoresces. The organisms are then scored as ``on`` or ``off`` with respect to free umbelliferone. This endpoint can then be usedmore » to calculate an EC50, which is comparable to a whole effluent, pure compound, or sediment toxicity test. Slightly different methodologies are used for different toxicity test organisms. The objective of this presentation is to discuss the use of the IQ{trademark} methodology with porewater extract exposures of the amphipod Hyalella azteca as a predictor of results of whole sediment toxicity tests. The results of over thirty 10 and 28-day whole sediment toxicity tests and the concurrent Hyalella azteca 10 TOXICITY TESTS{trademark} are compared and discussed. The use of screening tests as a reduced cost method for initial site assessment will be discussed.« less

Differences of wells scores accuracy, caprini scores and padua scores in deep vein thrombosis diagnosis

NASA Astrophysics Data System (ADS)

Gatot, D.; Mardia, A. I.

2018-03-01

Deep Vein Thrombosis (DVT) is the venous thrombus in lower limbs. Diagnosis is by using venography or ultrasound compression. However, these examinations are not available yet in some health facilities. Therefore many scoring systems are developed for the diagnosis of DVT. The scoring method is practical and safe to use in addition to efficacy, and effectiveness in terms of treatment and costs. The existing scoring systems are wells, caprini and padua score. There have been many studies comparing the accuracy of this score but not in Medan. Therefore, we are interested in comparative research of wells, capriniand padua score in Medan.An observational, analytical, case-control study was conducted to perform diagnostic tests on the wells, caprini and padua score to predict the risk of DVT. The study was at H. Adam Malik Hospital in Medan.From a total of 72 subjects, 39 people (54.2%) are men and the mean age are 53.14 years. Wells score, caprini score and padua score has a sensitivity of 80.6%; 61.1%, 50% respectively; specificity of 80.65; 66.7%; 75% respectively, and accuracy of 87.5%; 64.3%; 65.7% respectively.Wells score has better sensitivity, specificity and accuracy than caprini and padua score in diagnosing DVT.

The effects of calculator-based laboratories on standardized test scores

NASA Astrophysics Data System (ADS)

Stevens, Charlotte Bethany Rains

Nationwide, the goal of providing a productive science and math education to our youth in today's educational institutions is centering itself around the technology being utilized in these classrooms. In this age of digital technology, educational software and calculator-based laboratories (CBL) have become significant devices in the teaching of science and math for many states across the United States. Among the technology, the Texas Instruments graphing calculator and Vernier Labpro interface, are among some of the calculator-based laboratories becoming increasingly popular among middle and high school science and math teachers in many school districts across this country. In Tennessee, however, it is reported that this type of technology is not regularly utilized at the student level in most high school science classrooms, especially in the area of Physical Science (Vernier, 2006). This research explored the effect of calculator based laboratory instruction on standardized test scores. The purpose of this study was to determine the effect of traditional teaching methods versus graphing calculator teaching methods on the state mandated End-of-Course (EOC) Physical Science exam based on ability, gender, and ethnicity. The sample included 187 total tenth and eleventh grade physical science students, 101 of which belonged to a control group and 87 of which belonged to the experimental group. Physical Science End-of-Course scores obtained from the Tennessee Department of Education during the spring of 2005 and the spring of 2006 were used to examine the hypotheses. The findings of this research study suggested the type of teaching method, traditional or calculator based, did not have an effect on standardized test scores. However, the students' ability level, as demonstrated on the End-of-Course test, had a significant effect on End-of-Course test scores. This study focused on a limited population of high school physical science students in the middle Tennessee

OBSERVATIONS ON THE PRESENCE OF A TOXIC SUBSTANCE IN THE BLOOD AND URINE OF PATIENTS WITH SCARLET FEVER

PubMed Central

Trask, James D.; Blake, Francis G.

1924-01-01

A series of observations on the blood of patients acutely ill with scarlet fever has shown that a toxic substance can be demonstrated in the serum by means of intracutaneous injections of the serum in persons who have not had scarlet fever and whose serums fail to blanch the rash in scarlet fever. The reaction caused by this substance consists of a bright red local erythema, varying from 20 to 70 mm. in diameter, of 1 to 4 days duration. The severer reactions are moderately indurated and tender, and are followed bypigmentation and desquamation. Control injections in persons whose serums blanch the rash in scarlet fever cause no reaction. The toxic substance is not neutralized by mixture with a human serum which gives a negative blanching test but is readily neutralized by a human serum which gives a positive blanching test. It is not neutralized by normal horse serum, but is completely neutralized by Dochez's scarlatinal antistreptococcic serum. In a limited number of observations on the urine of patients with scarlet fever a similar toxic substance has been found in two out of five cases studied. Since the toxic substance described appears to resemble the toxic substance found in the filtrates of scarlatinal hemolytic streptococcus cultures by Dick and Dick and since it is neutralized not only by a blanching human serum but also by Dochez's scarlatinal antistreptococcic horse serum, the experiments reported support the conception that scarlet fever is a local infection of the throat by a particular type of Streptococcus hæmolyticus capable of producing a toxin which is absorbed and is the cause of the general manifestations of the disease. PMID:19868926

Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms.

PubMed

Rogosnitzky, Moshe; Branch, Stacy

2016-06-01

Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd(3+)) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden.

Discrimination of Native-like States of Membrane Proteins with Implicit Membrane-based Scoring Functions.

PubMed

Dutagaci, Bercem; Wittayanarakul, Kitiyaporn; Mori, Takaharu; Feig, Michael

2017-06-13

A scoring protocol based on implicit membrane-based scoring functions and a new protocol for optimizing the positioning of proteins inside the membrane was evaluated for its capacity to discriminate native-like states from misfolded decoys. A decoy set previously established by the Baker lab (Proteins: Struct., Funct., Genet. 2006, 62, 1010-1025) was used along with a second set that was generated to cover higher resolution models. The Implicit Membrane Model 1 (IMM1), IMM1 model with CHARMM 36 parameters (IMM1-p36), generalized Born with simple switching (GBSW), and heterogeneous dielectric generalized Born versions 2 (HDGBv2) and 3 (HDGBv3) were tested along with the new HDGB van der Waals (HDGBvdW) model that adds implicit van der Waals contributions to the solvation free energy. For comparison, scores were also calculated with the distance-scaled finite ideal-gas reference (DFIRE) scoring function. Z-scores for native state discrimination, energy vs root-mean-square deviation (RMSD) correlations, and the ability to select the most native-like structures as top-scoring decoys were evaluated to assess the performance of the scoring functions. Ranking of the decoys in the Baker set that were relatively far from the native state was challenging and dominated largely by packing interactions that were captured best by DFIRE with less benefit of the implicit membrane-based models. Accounting for the membrane environment was much more important in the second decoy set where especially the HDGB-based scoring functions performed very well in ranking decoys and providing significant correlations between scores and RMSD, which shows promise for improving membrane protein structure prediction and refinement applications. The new membrane structure scoring protocol was implemented in the MEMScore web server ( http://feiglab.org/memscore ).

Toxicity and efficacy of carbon nanotubes and graphene: the utility of carbon-based nanoparticles in nanomedicine.

PubMed

Zhang, Yongbin; Petibone, Dayton; Xu, Yang; Mahmood, Meena; Karmakar, Alokita; Casciano, Dan; Ali, Syed; Biris, Alexandru S

2014-05-01

Carbon-based nanomaterials have attracted great interest in biomedical applications such as advanced imaging, tissue regeneration, and drug or gene delivery. The toxicity of the carbon nanotubes and graphene remains a debated issue although many toxicological studies have been reported in the scientific community. In this review, we summarize the biological effects of carbon nanotubes and graphene in terms of in vitro and in vivo toxicity, genotoxicity and toxicokinetics. The dose, shape, surface chemistry, exposure route and purity play important roles in the metabolism of carbon-based nanomaterials resulting in differential toxicity. Careful examination of the physico-chemical properties of carbon-based nanomaterials is considered a basic approach to correlate the toxicological response with the unique properties of the carbon nanomaterials. The reactive oxygen species-mediated toxic mechanism of carbon nanotubes has been extensively discussed and strategies, such as surface modification, have been proposed to reduce the toxicity of these materials. Carbon-based nanomaterials used in photothermal therapy, drug delivery and tissue regeneration are also discussed in this review. The toxicokinetics, toxicity and efficacy of carbon-based nanotubes and graphene still need to be investigated further to pave a way for biomedical applications and a better understanding of their potential applications to humans.

Median Growth Percentiles (MGPs): Assessment of Intertemporal Stability and Correlations with Observational Scores

ERIC Educational Resources Information Center

Pivovarova, Margarita; Amrein-Beardsley, Audrey

2018-01-01

While states are no longer required to set up teacher evaluation systems based in significant part on student test scores, quite a few continue to use value-added (VAMs) or student growth percentile (SGP) models for that purpose. In this study, we analyzed three years of teacher data to illustrate the performance of teachers' median growth…

A portable cell-based impedance sensor for toxicity testing of drinking water.

PubMed

Curtis, Theresa M; Widder, Mark W; Brennan, Linda M; Schwager, Steven J; van der Schalie, William H; Fey, Julien; Salazar, Noe

2009-08-07

A major limitation to using mammalian cell-based biosensors for field testing of drinking water samples is the difficulty of maintaining cell viability and sterility without an on-site cell culture facility. This paper describes a portable automated bench-top mammalian cell-based toxicity sensor that incorporates enclosed fluidic biochips containing endothelial cells monitored by Electric Cell-substrate Impedance Sensing (ECIS) technology. Long-term maintenance of cells on the biochips is made possible by using a compact, self-contained disposable media delivery system. The toxicity sensor monitors changes in impedance of cell monolayers on the biochips after the introduction of water samples. The fluidic biochip includes an ECIS electronic layer and a polycarbonate channel layer, which together reduce initial impedance disturbances seen in commercially available open well ECIS chips caused by the mechanics of pipetting while maintaining the ability of the cells to respond to toxicants. A curve discrimination program was developed that compares impedance values over time between the control and treatment channels on the fluidic biochip and determines if they are significantly different. Toxicant responses of bovine pulmonary artery endothelial cells grown on fluidic biochips are similar to cells on commercially-available open well chips, and these cells can be maintained in the toxicity sensor device for at least nine days using an automated media delivery system. Longer-term cell storage is possible; bovine lung microvessel endothelial cells survive for up to four months on the fluidic biochips and remain responsive to a model toxicant. This is the first demonstration of a portable bench top system capable of both supporting cell health over extended periods of time and obtaining impedance measurements from endothelial cell monolayers after toxicant exposure.

Complex Mixture-Associated Hormesis and Toxicity: The Case of Leather Tanning Industry

PubMed Central

Pagano, Giovanni; Castello, Giuseppe; Gallo, Marialuisa; Borriello, Ilaria; Guida, Marco

2008-01-01

A series of studies investigated the toxicities of tannery-derived complex mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries. Toxicity was evaluated by multiple bioassays including developmental defects and loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus and Sphaerechinus granularis), and algal growth inhibition (Dunaliella tertiolecta and Selenastrum capricornutum). Both VT and ST water extracts resulted in hormetic effects at concentrations ranging 0.1 to 0.3%, and toxicity at levels ≥1%, both in sea urchin embryo and sperm, and in algal growth bioassays. When comparing tannin-based tannery wastewater (TTW) vs. chromium-based tannery effluent (CTE), a hormesis to toxicity trend was observed for TTW both in terms of developmental and fertilization toxicity in sea urchins, and in algal growth inhibition, with hormetic effects at 0.1 to 0.2% TTW, and toxicity at TTW levels ≥1%. Unlike TTW, CTE showed a monotonic toxicity increase from the lowest tested level (0.1%) and CTE toxicity at higher levels was significantly more severe than TTW-induced toxicity. The results support the view that leather production utilizing tannins might be regarded as a more environmentally friendly procedure than chromium-based tanning process. PMID:19088903

From scores to face templates: a model-based approach.

PubMed

Mohanty, Pranab; Sarkar, Sudeep; Kasturi, Rangachar

2007-12-01

Regeneration of templates from match scores has security and privacy implications related to any biometric authentication system. We propose a novel paradigm to reconstruct face templates from match scores using a linear approach. It proceeds by first modeling the behavior of the given face recognition algorithm by an affine transformation. The goal of the modeling is to approximate the distances computed by a face recognition algorithm between two faces by distances between points, representing these faces, in an affine space. Given this space, templates from an independent image set (break-in) are matched only once with the enrolled template of the targeted subject and match scores are recorded. These scores are then used to embed the targeted subject in the approximating affine (non-orthogonal) space. Given the coordinates of the targeted subject in the affine space, the original template of the targeted subject is reconstructed using the inverse of the affine transformation. We demonstrate our ideas using three, fundamentally different, face recognition algorithms: Principal Component Analysis (PCA) with Mahalanobis cosine distance measure, Bayesian intra-extrapersonal classifier (BIC), and a feature-based commercial algorithm. To demonstrate the independence of the break-in set with the gallery set, we select face templates from two different databases: Face Recognition Grand Challenge (FRGC) and Facial Recognition Technology (FERET) Database (FERET). With an operational point set at 1 percent False Acceptance Rate (FAR) and 99 percent True Acceptance Rate (TAR) for 1,196 enrollments (FERET gallery), we show that at most 600 attempts (score computations) are required to achieve a 73 percent chance of breaking in as a randomly chosen target subject for the commercial face recognition system. With similar operational set up, we achieve a 72 percent and 100 percent chance of breaking in for the Bayesian and PCA based face recognition systems, respectively. With

Discriminating modes of toxic action in mice using toxicity in BALB/c mouse fibroblast (3T3) cells.

PubMed

Huang, Tao; Yan, Lichen; Zheng, Shanshan; Wang, Yue; Wang, Xiaohong; Fan, Lingyun; Li, Chao; Zhao, Yuanhui; Martyniuk, Christopher J

2017-12-01

The objective of this study was to determine whether toxicity in mouse fibroblast cells (3T3 cells) could predict toxicity in mice. Synthesized data on toxicity was subjected to regression analysis and it was observed that relationship of toxicities between mice and 3T3 cells was not strong (R 2  = 0.41). Inclusion of molecular descriptors (e.g. ionization, pKa) improved the regression to R 2  = 0.56, indicating that this relationship is influenced by kinetic processes of chemicals or specific toxic mechanisms associated to the compounds. However, to determine if we were able to discriminate modes of action (MOAs) in mice using the toxicities generated from 3T3 cells, compounds were first classified into "baseline" and "reactive" guided by the toxic ratio (TR) for each compound in mice. Sequence, binomial and recursive partitioning analyses provided strong predictions of MOAs in mice based upon toxicities in 3T3 cells. The correct classification of MOAs based on these methods was 86%. Nearly all the baseline compounds predicted from toxicities in 3T3 cells were identified as baseline compounds from the TR in mice. The incorrect assignment of MOAs for some compounds is hypothesized to be due to experimental uncertainty that exists in toxicity assays for both mice and 3T3 cells. Conversely, lack of assignment can also arise because some reactive compounds have MOAs that are different in mice compared to 3T3 cells. The methods developed here are novel and contribute to efforts to reduce animal numbers in toxicity tests that are used to evaluate risks associated with organic pollutants in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

PubMed

Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

2018-06-01

G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

Sediment toxicity identification evaluation (TIE) studies at marine sites suspected of ordnance contamination

USGS Publications Warehouse

Carr, R.S.; Nipper, M.; Biedenbach, J.M.; Hooten, R.L.; Miller, K.; Saepoff, S.

2001-01-01

A sediment quality assessment survey and subsequent toxicity identification evaluation (TIE) study was conducted at several sites in Puget Sound, Washington. The sites were previously suspected of contamination with ordnance compounds. The initial survey employed sea urchin porewater toxicity tests to locate the most toxic stations. Sediments from the most toxic stations were selected for comprehensive chemical analyses. Based on the combined information from the toxicity and chemical data, three adjacent stations in Ostrich Bay were selected for the TIE study. The results of the phase I TIE suggested that organics and metals were primarily responsible for the observed toxicity in the sea urchin fertilization test. In addition to these contaminants, ammonia was also contributing to the toxicity for the sea urchin embryological development test. The phase II TIE study isolated the majority of the toxicity in the fraction containing nonpolar organics with high log Kow, but chemical analyses failed to identify a compound present at a concentration high enough to be responsible for the observed toxicity. The data suggest that some organic or organometallic contaminant(s) that were not included in the comprehensive suite of chemical analyses caused the observed toxicological responses.

Randomized clinical trial of Appendicitis Inflammatory Response score-based management of patients with suspected appendicitis.

PubMed

Andersson, M; Kolodziej, B; Andersson, R E

2017-10-01

The role of imaging in the diagnosis of appendicitis is controversial. This prospective interventional study and nested randomized trial analysed the impact of implementing a risk stratification algorithm based on the Appendicitis Inflammatory Response (AIR) score, and compared routine imaging with selective imaging after clinical reassessment. Patients presenting with suspicion of appendicitis between September 2009 and January 2012 from age 10 years were included at 21 emergency surgical centres and from age 5 years at three university paediatric centres. Registration of clinical characteristics, treatments and outcomes started during the baseline period. The AIR score-based algorithm was implemented during the intervention period. Intermediate-risk patients were randomized to routine imaging or selective imaging after clinical reassessment. The baseline period included 1152 patients, and the intervention period 2639, of whom 1068 intermediate-risk patients were randomized. In low-risk patients, use of the AIR score-based algorithm resulted in less imaging (19·2 versus 34·5 per cent; P < 0·001), fewer admissions (29·5 versus 42·8 per cent; P < 0·001), and fewer negative explorations (1·6 versus 3·2 per cent; P = 0·030) and operations for non-perforated appendicitis (6·8 versus 9·7 per cent; P = 0·034). Intermediate-risk patients randomized to the imaging and observation groups had the same proportion of negative appendicectomies (6·4 versus 6·7 per cent respectively; P = 0·884), number of admissions, number of perforations and length of hospital stay, but routine imaging was associated with an increased proportion of patients treated for appendicitis (53·4 versus 46·3 per cent; P = 0·020). AIR score-based risk classification can safely reduce the use of diagnostic imaging and hospital admissions in patients with suspicion of appendicitis. Registration number: NCT00971438 ( http://www.clinicaltrials.gov). © 2017 BJS

A cluster design controlled trial of arts-based observational skills training in primary care.

PubMed

Kirklin, Deborah; Duncan, Jane; McBride, Sandy; Hunt, Sam; Griffin, Mark

2007-04-01

To investigate whether the observational skills of doctors and nurses can be improved by arts-based observational skills training. We carried out a cluster design, controlled trial involving 42 general practitioners and 26 primary care nurses in 12 primary care practices in London. Six practices were allocated to the intervention arm and 6 to the control arm. The intervention group received 90 minutes of arts-based observational skills training. The control group received practical training in the management of psoriasis. Before and after this, control and intervention participants were asked to describe 3 dermatological photographs. Descriptions were scored blindly against a predetermined marking key. Participants completed a questionnaire about the intervention, and about their own confidence in diagnosing and referring suspicious pigmented skin lesions. Post-intervention scores were significantly higher in the intervention group compared with the control group (P < 0.001). The majority of participants judged the intervention relevant, enjoyable and valuable. A majority lacked confidence in their dermatological knowledge and skills. This study provides statistically significant evidence that arts-based observational skills training can improve the observational skills of doctors and nurses. It is important not to overstate the clinical significance of these findings, and to recognise that observational skills are just one of many complex and subtle factors affecting the quality of the clinical process. Further research is needed to assess the existence, nature and clinical significance of longer-term benefits, and to identify differences between professional groups.

Development of a food-based diet quality score for Japanese: associations of the score with nutrient intakes in young, middle-aged and older Japanese women.

PubMed

Kuriyama, Nozomi; Murakami, Kentaro; Livingstone, M Barbara E; Okubo, Hitomi; Kobayashi, Satomi; Suga, Hitomi; Sasaki, Satoshi

2016-01-01

Several previous studies have shown that a diet score based on the Japanese food guide Spinning Top (the original score) is associated with both favourable and unfavourable dietary intake patterns. We developed a food-based diet quality score (the modified score) and examined associations with nutrient intakes. Subjects were 3963 young (all aged 18 years), 3800 middle-aged (mean age 47·7 (sd 3·9) years) and 2211 older (mean age 74·4 (sd 5·2) years) Japanese women. Dietary intakes were assessed using comprehensive (for the young and middle-aged) and brief-type (for the older) diet history questionnaires. The original score was calculated based on intakes of grains, vegetables, fish/meat, milk, fruits, and snacks/alcoholic beverages. The modified score was similarly calculated, but included Na from seasonings and without applying the upper cut-off values for dietary components where increased consumption is advocated for Japanese women (grains, vegetables, fish/meat, milk, and fruits). The original score was positively associated with intakes of carbohydrate, dietary fibre, and all the vitamins and minerals examined including Na and inversely with intakes of fats and alcohol in young and middle-aged women. In older women, the original score was inversely associated with intakes of all nutrients except for carbohydrate and vitamin C. However, the modified score was associated positively with intakes of protein, carbohydrate, dietary fibre, K, Ca, Mg, Fe, vitamins A, C and E, and folate and inversely with intakes of fats, alcohol and Na in all generations. In conclusion, the modified diet score was positively associated with favourable nutrient intake patterns in Japanese women.

Development of a Food Group-Based Diet Score and Its Association with Bone Mineral Density in the Elderly: The Rotterdam Study.

PubMed

de Jonge, Ester A L; Kiefte-de Jong, Jessica C; de Groot, Lisette C P G M; Voortman, Trudy; Schoufour, Josje D; Zillikens, M Carola; Hofman, Albert; Uitterlinden, André G; Franco, Oscar H; Rivadeneira, Fernando

2015-08-18

No diet score exists that summarizes the features of a diet that is optimal for bone mineral density (BMD) in the elderly. Our aims were (a) to develop a BMD-Diet Score reflecting a diet that may be beneficial for BMD based on the existing literature, and (b) to examine the association of the BMD-Diet Score and the Healthy Diet Indicator, a score based on guidelines of the World Health Organization, with BMD in Dutch elderly participating in a prospective cohort study, the Rotterdam Study (n = 5144). Baseline dietary intake, assessed using a food frequency questionnaire, was categorized into food groups. Food groups that were consistently associated with BMD in the literature were included in the BMD-Diet Score. BMD was measured repeatedly and was assessed using dual energy X-ray absorptiometry. The BMD-Diet Score considered intake of vegetables, fruits, fish, whole grains, legumes/beans and dairy products as "high-BMD" components and meat and confectionary as "low-BMD" components. After adjustment, the BMD-Diet Score was positively associated with BMD (β (95% confidence interval) = 0.009 (0.005, 0.012) g/cm(2) per standard deviation). This effect size was approximately three times as large as has been observed for the Healthy Diet Indicator. The food groups included in our BMD-Diet Score could be considered in the development of future dietary guidelines for healthy ageing.

Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

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

Kelsey, Chris R., E-mail: kelse003@mc.duke.edu; Horwitz, Mitchell E.; Chino, Junzo P.

2011-11-01

Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meiermore » method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.« less

Clinical efficacy of polyspecific intravenous immunoglobulin therapy in patients with streptococcal toxic shock syndrome: a comparative observational study.

PubMed

Linnér, Anna; Darenberg, Jessica; Sjölin, Jan; Henriques-Normark, Birgitta; Norrby-Teglund, Anna

2014-09-15

Streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis are the 2 most severe invasive manifestations caused by group A Streptococcus (GAS). Intravenous immunoglobulin (IVIG) therapy has been suggested as adjunctive treatment with a beneficial effect on mortality. However the clinical evidence is limited. Here we aim to further document the clinical efficacy of administered IVIG therapy in a comparative observational study of well-defined patients with STSS. The effect of IVIG was evaluated in patients with STSS prospectively identified in a nationwide Swedish surveillance study conducted between April 2002 and December 2004. Detailed data on symptoms, severity of disease, treatment, and outcome were obtained from 67 patients. Crude and adjusted analyses with logistic regression were performed. Twenty-three patients received IVIG therapy compared with 44 who did not. No significant difference in comorbidities, severity of disease, organ failures, or sex was seen, but the IVIG group was slightly younger and had a higher degree of necrotizing fasciitis (56% vs 14%). The primary endpoint was 28-day survival. Adjusted analysis revealed that factors influencing survival in STSS were Simplified Acute Physiology Score II (odds ratio [OR], 1.1; P = .007), clindamycin (OR, 8.6; P = .007), and IVIG (OR, 5.6; P = .030). This comparative observational study of prospectively identified STSS patients demonstrates that both IVIG and clindamycin therapy contribute to a significantly improved survival in STSS. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats.

PubMed

Zhang, Xiaofang; Zhang, Xiaodong; Yuan, Bojun; Ren, Lijun; Zhang, Tianbao; Lu, Guocai

2016-11-30

Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD) rats was identified. Dogs and rats received HZ1006 orally (0-80 and 0-120 mg/kg/day, respectively) on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006's NOAEL (No Observed Adverse Effect Level) by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

Hydrogel Based 3-Dimensional (3D) System for Toxicity and High-Throughput (HTP) Analysis for Cultured Murine Ovarian Follicles

PubMed Central

Zhou, Hong; Malik, Malika Amattullah; Arab, Aarthi; Hill, Matthew Thomas; Shikanov, Ariella

2015-01-01

Various toxicants, drugs and their metabolites carry potential ovarian toxicity. Ovarian follicles, the functional unit of the ovary, are susceptible to this type of damage at all stages of their development. However, despite of the large scale of potential negative impacts, assays that study ovarian toxicity are limited. Exposure of cultured ovarian follicles to toxicants of interest served as an important tool for evaluation of toxic effects for decades. Mouse follicles cultured on the bottom of a culture dish continue to serve an important approach for mechanistic studies. In this paper, we demonstrated the usefulness of a hydrogel based 3-dimensional (3D) mouse ovarian follicle culture as a tool to study ovarian toxicity in a different setup. The 3D in vitro culture, based on fibrin alginate interpenetrating network (FA-IPN), preserves the architecture of the ovarian follicle and physiological structure-function relationship. We applied the novel 3D high-throughput (HTP) in vitro ovarian follicle culture system to study the ovotoxic effects of an anti-cancer drug, Doxorobucin (DXR). The fibrin component in the system is degraded by plasmin and appears as a clear circle around the encapsulated follicle. The degradation area of the follicle is strongly correlated with follicle survival and growth. To analyze fibrin degradation in a high throughput manner, we created a custom MATLAB® code that converts brightfield micrographs of follicles encapsulated in FA-IPN to binary images, followed by image analysis. We did not observe any significant difference between manually processed images to the automated MATLAB® method, thereby confirming that the automated program is suitable to measure fibrin degradation to evaluate follicle health. The cultured follicles were treated with DXR at concentrations ranging from 0.005 nM to 200 nM, corresponding to the therapeutic plasma levels of DXR in patients. Follicles treated with DXR demonstrated decreased survival rate in

Structure-based drug design: docking and scoring.

PubMed

Kroemer, Romano T

2007-08-01

This review gives an introduction into ligand - receptor docking and illustrates the basic underlying concepts. An overview of different approaches and algorithms is provided. Although the application of docking and scoring has led to some remarkable successes, there are still some major challenges ahead, which are outlined here as well. Approaches to address some of these challenges and the latest developments in the area are presented. Some aspects of the assessment of docking program performance are discussed. A number of successful applications of structure-based virtual screening are described.

Toxic Shock Syndrome Caused by Methicillin-Resistant Staphylococcus aureus (MRSA) After Expander-Based Breast Reconstruction.

PubMed

Suga, Hirotaka; Shiraishi, Tomohiro; Takushima, Akihiko; Harii, Kiyonori

2016-01-01

Toxic shock syndrome is a rare but life-threatening complication after plastic surgery procedures. We experienced 2 cases of toxic shock syndrome after expander-based breast reconstruction caused by methicillin-resistant Staphylococcus aureus. The first patient took a severe clinical course due to the delayed diagnosis and treatment, and the second patient recovered rapidly after the early diagnosis and treatment based on our experience of the first case. Fever, rash, and gastrointestinal symptoms (diarrhea and/or vomiting) were characteristic and important for the early diagnosis of toxic shock syndrome. Considering the increased prevalence of methicillin-resistant Staphylococcus aureus, we should suspect methicillin-resistant Staphylococcus aureus in cases of toxic shock syndrome that occur postoperatively, and the empiric administration of vancomycin should be initiated in such cases.

An evidence-based approach to the creation of normative data: base rates of impaired scores within a brief neuropsychological battery argue for age corrections, but against corrections for medical conditions.

PubMed

O'Connell, Megan E; Tuokko, Holly; Voll, Stacey; Simard, Martine; Griffith, Lauren E; Taler, Vanessa; Wolfson, Christina; Kirkland, Susan; Raina, Parminder

We detail a new approach to the creation of normative data for neuropsychological tests. The traditional approach to normative data creation is to make demographic adjustments based on observations of correlations between single neuropsychological tests and selected demographic variables. We argue, however, that this does not describe the implications for clinical practice, such as increased likelihood of misclassification of cognitive impairment, nor does it elucidate the impact on decision-making with a neuropsychological battery. We propose base rate analyses; specifically, differential base rates of impaired scores between theoretical and actual base rates as the basis for decisions to create demographic adjustments within normative data. Differential base rates empirically describe the potential clinical implications of failing to create an appropriate normative group. We demonstrate this approach with data from a short telephone-administered neuropsychological battery given to a large, neurologically healthy sample aged 45-85 years old. We explored whether adjustments for age and medical conditions were warranted based on differential base rates of spuriously impaired scores. Theoretical base rates underestimated the frequency of impaired scores in older adults and overestimated the frequency of impaired scores in younger adults, providing an evidence base for the creation of age-corrected normative data. In contrast, the number of medical conditions (numerous cardiovascular, hormonal, and metabolic conditions) was not related to differential base rates of impaired scores. Despite a small correlation between number of medical conditions and each neuropsychological variable, normative adjustments for number of medical conditions does not appear warranted. Implications for creation of normative data are discussed.

Slit Lamp-Based Ocular Scoring Systems in Toxicology and Drug Development: A Literature Survey.

PubMed

Eaton, Joshua Seth; Miller, Paul E; Bentley, Ellison; Thomasy, Sara M; Murphy, Christopher J

2017-12-01

To present a survey of the features of published slit lamp-based scoring systems and their applicability in the context of modern ocular toxicology and drug development. References describing original or modified slit lamp-based scoring systems for human or veterinary clinical patients or in investigative or toxicologic research were collected following a comprehensive literature review using textbooks and online publication searches. Each system's indications and features were compiled to facilitate comparison. Literature review identified 138 original or modified scoring systems. Most (48%) were published for evaluation of the ocular surface, 34% for the general anterior segment, and 18% for the lens. Most systems were described for assessment of human patients (50%) and small albino laboratory species such as rabbits (19%), rats (12%), and mice (8%). Systems described for pigmented laboratory species and for larger species such as dogs, cats, pigs, and nonhuman primates (NHPs) were comparatively underrepresented. No systems described a lens scoring scheme specific to the dog, cat, pig, or NHP. Scoring schemes for aqueous and vitreous cells were infrequently described for laboratory species. Many slit lamp-based scoring systems have been published, but the features of each differ and complicate translation of findings between different species. Use and interpretation of any scoring system in toxicology and drug development must be done with awareness of the limitations of the system being used.

Bias reduction in repeated-measures observational studies by the use of propensity score: the case of enteral sedation for critically ill patients.

PubMed

Umbrello, Michele; Mistraletti, Giovanni; Corbella, Davide; Cigada, Marco; Salini, Silvia; Morabito, Alberto; Iapichino, Gaetano

2012-12-01

Within the evidence-based medicine paradigm, randomized controlled trials represent the "gold standard" to produce reliable evidence. Indeed, planning and implementing randomized controlled trials in critical care medicine presents limitations because of intrinsic and structural problems. As a consequence, observational studies still occur frequently. In these cases, propensity score (PS) (probability of receiving a treatment conditional on observed covariates) is an increasingly used technique to adjust the results. Few studies addressed the specific issue of a PS correction of repeated-measures designs. Three techniques for correcting the analysis of nonrandomized designs (matching, stratification, regression adjustment) are presented in a tutorial form and applied to a real case study: the comparison between intravenous and enteral sedative therapy in the intensive care unit setting. After showing the results before and after the use of PS, we suggest that such a tool allows to partially overcoming the bias associated with the observational nature of the study. It permits to correct the estimates for any observed covariate, while unobserved confounders cannot be controlled for. Propensity score represents a useful additional tool to estimate the effects of treatments in nonrandomized studies. In the case study, an enteral sedation approach was equally effective to an intravenous regime, allowing for a lower level of sedation and spare of resources. Copyright © 2012 Elsevier Inc. All rights reserved.

Toxicity of a plant based mosquito repellent/killer.

PubMed

Singh, Bhoopendra; Singh, Prakash Raj; Mohanty, Manoj Kumar

2012-12-01

The mission to make humans less attractive to mosquitoes has fuelled decades of scientific research on mosquito behaviour and control. The search for the perfect topical insect repellent/killer continues. This analysis was conducted to review and explore the scientific information on toxicity produced by the ingredients/contents of a herbal product. In this process of systemic review the following methodology was applied. By doing a MEDLINE search with key words of selected plants, plant based insect repellents/killers pertinent articles published in journals and authentic books were reviewed. The World Wide Web and the Extension Toxicity Network database (IPCS-ITOX) were also searched for toxicology data and other pertinent information. Repellents do not all share a single mode of action and surprisingly little is known about how repellents act on their target insects. Moreover, different mosquito species may react differently to the same repellent. After analysis of available data and information on the ingredient, of the product in relation to medicinal uses, acute and chronic toxicity of the selected medicinal plants, it can be concluded that the ingredients included in the herbal product can be used as active agents against mosquitoes. If the product which contains the powder of the above said plants is applied with care and safety, it is suitable fo use as a mosquito repellent/killer.

Toxicity of a plant based mosquito repellent/killer

PubMed Central

Singh, Prakash Raj; Mohanty, Manoj Kumar

2012-01-01

The mission to make humans less attractive to mosquitoes has fuelled decades of scientific research on mosquito behaviour and control. The search for the perfect topical insect repellent/killer continues. This analysis was conducted to review and explore the scientific information on toxicity produced by the ingredients/contents of a herbal product. In this process of systemic review the following methodology was applied. By doing a MEDLINE search with key words of selected plants, plant based insect repellents/killers pertinent articles published in journals and authentic books were reviewed. The World Wide Web and the Extension Toxicity Network database (IPCS-ITOX) were also searched for toxicology data and other pertinent information. Repellents do not all share a single mode of action and surprisingly little is known about how repellents act on their target insects. Moreover, different mosquito species may react differently to the same repellent. After analysis of available data and information on the ingredient, of the product in relation to medicinal uses, acute and chronic toxicity of the selected medicinal plants, it can be concluded that the ingredients included in the herbal product can be used as active agents against mosquitoes. If the product which contains the powder of the above said plants is applied with care and safety, it is suitable fo use as a mosquito repellent/killer. PMID:23554562

Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

NASA Astrophysics Data System (ADS)

Harper, Bryan; Thomas, Dennis; Chikkagoudar, Satish; Baker, Nathan; Tang, Kaizhi; Heredia-Langner, Alejandro; Lins, Roberto; Harper, Stacey

2015-06-01

The integration of rapid assays, large datasets, informatics, and modeling can overcome current barriers in understanding nanomaterial structure-toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here, we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality in developing embryonic zebrafish, were established at realistic exposure levels and used to develop a hazard ranking of diverse nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both the core composition and outermost surface chemistry of nanomaterials. The resulting clusters guided the development of a surface chemistry-based model of gold nanoparticle toxicity. Our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. Research should continue to focus on methodologies for determining nanomaterial hazard based on multiple sub-lethal responses following realistic, low-dose exposures, thus increasing the availability of quantitative measures of nanomaterial hazard to support the development of nanoparticle structure-activity relationships.

Advanced clinical interpretation of the Delis-Kaplan Executive Function System: multivariate base rates of low scores.

PubMed

Karr, Justin E; Garcia-Barrera, Mauricio A; Holdnack, James A; Iverson, Grant L

2018-01-01

Multivariate base rates allow for the simultaneous statistical interpretation of multiple test scores, quantifying the normal frequency of low scores on a test battery. This study provides multivariate base rates for the Delis-Kaplan Executive Function System (D-KEFS). The D-KEFS consists of 9 tests with 16 Total Achievement scores (i.e. primary indicators of executive function ability). Stratified by education and intelligence, multivariate base rates were derived for the full D-KEFS and an abbreviated four-test battery (i.e. Trail Making, Color-Word Interference, Verbal Fluency, and Tower Test) using the adult portion of the normative sample (ages 16-89). Multivariate base rates are provided for the full and four-test D-KEFS batteries, calculated using five low score cutoffs (i.e. ≤25th, 16th, 9th, 5th, and 2nd percentiles). Low scores occurred commonly among the D-KEFS normative sample, with 82.6 and 71.8% of participants obtaining at least one score ≤16th percentile for the full and four-test batteries, respectively. Intelligence and education were inversely related to low score frequency. The base rates provided herein allow clinicians to interpret multiple D-KEFS scores simultaneously for the full D-KEFS and an abbreviated battery of commonly administered tests. The use of these base rates will support clinicians when differentiating between normal variations in cognitive performance and true executive function deficits.

SCORE - Sounding-rocket Coronagraphic Experiment

NASA Astrophysics Data System (ADS)

Fineschi, Silvano; Moses, Dan; Romoli, Marco

The Sounding-rocket Coronagraphic Experiment - SCORE - is a The Sounding-rocket Coronagraphic Experiment - SCORE - is a coronagraph for multi-wavelength imaging of the coronal Lyman-alpha lines, HeII 30.4 nm and HI 121.6 nm, and for the broad.band visible-light emission of the polarized K-corona. SCORE has flown successfully in 2009 acquiring the first images of the HeII line-emission from the extended corona. The simultaneous observation of the coronal Lyman-alpha HI 121.6 nm, has allowed the first determination of the absolute helium abundance in the extended corona. This presentation will describe the lesson learned from the first flight and will illustrate the preparations and the science perspectives for the second re-flight approved by NASA and scheduled for 2016. The SCORE optical design is flexible enough to be able to accommodate different experimental configurations with minor modifications. This presentation will describe one of such configurations that could include a polarimeter for the observation the expected Hanle effect in the coronal Lyman-alpha HI line. The linear polarization by resonance scattering of coronal permitted line-emission in the ultraviolet (UV) can be modified by magnetic fields through the Hanle effect. Thus, space-based UV spectro-polarimetry would provide an additional new tool for the diagnostics of coronal magnetism.

Toxicity studies of a polyurethane rigid foam

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Schneider, J. E.

1977-01-01

Relative toxicity tests were performed on a polyurethane foam containing a trimethylopropane-based polyol and an organophosphate flame retardant. The routine screening procedure involved the exposure of four Swiss albino male mice in a 4.2 liter hemispherical chamber to the products generated by pyrolyzing a 1.00 g sample at a heating rate of 40 deg C/min from 200 to 800 C in the absence of air flow. In addition to the routine screening, experiments were performed with a very rapid rise to 800 C, with nominal 16 and 48 ml/sec air flow and with varying sample rates. No unusual toxicity was observed with either gradual or rapid pyrolysis to 800 C. Convulsions and seizures similar to those previously reported were observed when the materials were essentially flash pyrolyzed at 800 C in the presence of air flow, and the toxicity appeared unusual because of low sample weights required to produce death.

The effects of sperminated pullulans on cornea permeability to puerarin and the toxicity.

PubMed

Yu, Nannan; Dong, Guo; Ge, Hongyan; Jin, Di; Cui, Hao; Liu, Ping

2012-10-01

To investigate the varied effects of sperminated pullulans (SP) with different amino residues on cornea permeability and its local toxicity. Three groups of rabbits were used: control, low-amino residue content SP (SP-L), and high-amino residue content SP (SP-H). The in vitro and in vivo spreading assays were combined with high performance liquid chromatography (HPLC) to measure the concentration of puerarin in the external medium or aqueous humor when 0% SP, 0.2% SP-L, and 0.2% SP-H were included. The toxicity of SP was determined by corneal hydration values, Draize score, aqueous humor protein concentration, corneal endothelial evaluation, as well as light microscopy and electron microscopy. The application of 0.2% SP-L and 0.2% SP-H to the cornea in vitro increased puerarin apparent permeability coefficient by 1.96-fold (P<0.05) and 2.95-fold (P<0.01), respectively. SP-H showed stronger effect than SP-L (P<0.05). For the in vivo assay, those were 1.81-fold (P<0.05) and 3.71-fold (P<0.01), respectively. With the SP application, the corneal hydration values were <83% and Draize scores were <4, with no apparent changes in histological observations. SP is one potential adjuvant promoting puerarin permeability to the cornea, and the high-content amino residue SP showed stronger effect, without ocular toxicity.

Predictors for Rectal and Intestinal Acute Toxicities During Prostate Cancer High-Dose 3D-CRT: Results of a Prospective Multicenter Study

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

Vavassori, Vittorio; Fiorino, Claudio; Rancati, Tiziana

2007-04-01

Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with {>=}70 Gy conformal radiotherapy. Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/severe complications were considered. Results: Of 1,132more » patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p = 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p 0.02; odds ratio, 0.63) and hormonal therapy (p = 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea. Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently

NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis.

PubMed

Lienemann, Kai; Plötz, Thomas; Pestel, Sabine

2008-01-01

The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

Computerized summary scoring: crowdsourcing-based latent semantic analysis.

PubMed

Li, Haiying; Cai, Zhiqiang; Graesser, Arthur C

2017-11-03

In this study we developed and evaluated a crowdsourcing-based latent semantic analysis (LSA) approach to computerized summary scoring (CSS). LSA is a frequently used mathematical component in CSS, where LSA similarity represents the extent to which the to-be-graded target summary is similar to a model summary or a set of exemplar summaries. Researchers have proposed different formulations of the model summary in previous studies, such as pregraded summaries, expert-generated summaries, or source texts. The former two methods, however, require substantial human time, effort, and costs in order to either grade or generate summaries. Using source texts does not require human effort, but it also does not predict human summary scores well. With human summary scores as the gold standard, in this study we evaluated the crowdsourcing LSA method by comparing it with seven other LSA methods that used sets of summaries from different sources (either experts or crowdsourced) of differing quality, along with source texts. Results showed that crowdsourcing LSA predicted human summary scores as well as expert-good and crowdsourcing-good summaries, and better than the other methods. A series of analyses with different numbers of crowdsourcing summaries demonstrated that the number (from 10 to 100) did not significantly affect performance. These findings imply that crowdsourcing LSA is a promising approach to CSS, because it saves human effort in generating the model summary while still yielding comparable performance. This approach to small-scale CSS provides a practical solution for instructors in courses, and also advances research on automated assessments in which student responses are expected to semantically converge on subject matter content.

The value of Bayes' theorem for interpreting abnormal test scores in cognitively healthy and clinical samples.

PubMed

Gavett, Brandon E

2015-03-01

The base rates of abnormal test scores in cognitively normal samples have been a focus of recent research. The goal of the current study is to illustrate how Bayes' theorem uses these base rates--along with the same base rates in cognitively impaired samples and prevalence rates of cognitive impairment--to yield probability values that are more useful for making judgments about the absence or presence of cognitive impairment. Correlation matrices, means, and standard deviations were obtained from the Wechsler Memory Scale--4th Edition (WMS-IV) Technical and Interpretive Manual and used in Monte Carlo simulations to estimate the base rates of abnormal test scores in the standardization and special groups (mixed clinical) samples. Bayes' theorem was applied to these estimates to identify probabilities of normal cognition based on the number of abnormal test scores observed. Abnormal scores were common in the standardization sample (65.4% scoring below a scaled score of 7 on at least one subtest) and more common in the mixed clinical sample (85.6% scoring below a scaled score of 7 on at least one subtest). Probabilities varied according to the number of abnormal test scores, base rates of normal cognition, and cutoff scores. The results suggest that interpretation of base rates obtained from cognitively healthy samples must also account for data from cognitively impaired samples. Bayes' theorem can help neuropsychologists answer questions about the probability that an individual examinee is cognitively healthy based on the number of abnormal test scores observed.

Schooling in adolescence raises IQ scores

PubMed Central

Brinch, Christian N.; Galloway, Taryn Ann

2012-01-01

Although some scholars maintain that education has little effect on intelligence quotient (IQ) scores, others claim that IQ scores are indeed malleable, primarily through intervention in early childhood. The causal effect of education on IQ at later ages is often difficult to uncover because analyses based on observational data are plagued by problems of reverse causation and self-selection into further education. We exploit a reform that increased compulsory schooling from 7 to 9 y in Norway in the 1960s to estimate the effect of education on IQ. We find that this schooling reform, which primarily affected education in the middle teenage years, had a substantial effect on IQ scores measured at the age of 19 y. PMID:22203952

Re-irradiation: outcome, cumulative dose and toxicity in patients retreated with stereotactic radiotherapy in the abdominal or pelvic region.

PubMed

Abusaris, Huda; Hoogeman, M; Nuyttens, Joost J

2012-12-01

The purpose of the present study was to explore the outcome, cumulative dose in tumor and organs at risk and toxicity after extra-cranial stereotactic re-irradiation. Twenty-seven patients were evaluated who had been re-irradiated with stereotactic body radiotherapy (SBRT) after conventional radiotherapy (CRT). The dose summation of the SBRT and CRT plans was done by dose point calculations accounting for fraction size by the linear-quadratic model. Efficacy and toxicity was scored by looking at the reduction in tumor size, pain and bleeding. Symptomatic response was observed in 96% of the patients. The median maximum SBRT dose to the tumor was 90 Gy(3) (range: 42-420 Gy(3)). The median cumulative dose for the rectum, bowel and bladder resulted in 104 Gy(3), 98 Gy(3) and 113 Gy(3), respectively. No grades 5, 4 and 3 acute and late toxicity was observed. re-irradiation to the same region using extra-cranial stereotactic radiotherapy is feasible and resulted in a 96% symptomatic response with low toxicity.

Accounting for Intraligand Interactions in Flexible Ligand Docking with a PMF-Based Scoring Function.

PubMed

Lizunov, A Y; Gonchar, A L; Zaitseva, N I; Zosimov, V V

2015-10-26

We analyzed the frequency with which intraligand contacts occurred in a set of 1300 protein-ligand complexes [ Plewczynski et al. J. Comput. Chem. 2011 , 32 , 742 - 755 .]. Our analysis showed that flexible ligands often form intraligand hydrophobic contacts, while intraligand hydrogen bonds are rare. The test set was also thoroughly investigated and classified. We suggest a universal method for enhancement of a scoring function based on a potential of mean force (PMF-based score) by adding a term accounting for intraligand interactions. The method was implemented via in-house developed program, utilizing an Algo_score scoring function [ Ramensky et al. Proteins: Struct., Funct., Genet. 2007 , 69 , 349 - 357 .] based on the Tarasov-Muryshev PMF [ Muryshev et al. J. Comput.-Aided Mol. Des. 2003 , 17 , 597 - 605 .]. The enhancement of the scoring function was shown to significantly improve the docking and scoring quality for flexible ligands in the test set of 1300 protein-ligand complexes [ Plewczynski et al. J. Comput. Chem. 2011 , 32 , 742 - 755 .]. We then investigated the correlation of the docking results with two parameters of intraligand interactions estimation. These parameters are the weight of intraligand interactions and the minimum number of bonds between the ligand atoms required to take their interaction into account.

A Computer Based Program to Improve Reading and Mathematics Scores for High School Students.

ERIC Educational Resources Information Center

Bond, Carole L.; And Others

A study examined the effect on reading achievement, mathematics achievement, and ACT scores when computer based instruction (CBI) was compressed into a 6-week period of time. In addition, the effects of learning style and receptive language deficits on these scores were studied. Computer based instruction is a primary source of instruction that…

Differential Weighting for Subcomponent Measures of Integrated Clinical Encounter Scores Based on the USMLE Step 2 CS Examination: Effects on Composite Score Reliability and Pass-Fail Decisions.

PubMed

Park, Yoon Soo; Lineberry, Matthew; Hyderi, Abbas; Bordage, Georges; Xing, Kuan; Yudkowsky, Rachel

2016-11-01

Medical schools administer locally developed graduation competency examinations (GCEs) following the structure of the United States Medical Licensing Examination Step 2 Clinical Skills that combine standardized patient (SP)-based physical examination and the patient note (PN) to create integrated clinical encounter (ICE) scores. This study examines how different subcomponent scoring weights in a locally developed GCE affect composite score reliability and pass-fail decisions for ICE scores, contributing to internal structure and consequential validity evidence. Data from two M4 cohorts (2014: n = 177; 2015: n = 182) were used. The reliability of SP encounter (history taking and physical examination), PN, and communication and interpersonal skills scores were estimated with generalizability studies. Composite score reliability was estimated for varying weight combinations. Faculty were surveyed for preferred weights on the SP encounter and PN scores. Composite scores based on Kane's method were compared with weighted mean scores. Faculty suggested weighting PNs higher (60%-70%) than the SP encounter scores (30%-40%). Statistically, composite score reliability was maximized when PN scores were weighted at 40% to 50%. Composite score reliability of ICE scores increased by up to 0.20 points when SP-history taking (SP-Hx) scores were included; excluding SP-Hx only increased composite score reliability by 0.09 points. Classification accuracy for pass-fail decisions between composite and weighted mean scores was 0.77; misclassification was < 5%. Medical schools and certification agencies should consider implications of assigning weights with respect to composite score reliability and consequences on pass-fail decisions.

[Preclinical prognosis of pyracetam and picamilon safety based on acute toxicity data].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

2003-01-01

A comparative acute toxicity test of the nootropic drugs piracetam and picamilon was performed on rats. The study was based on the principles of integral evaluation of the drug effect upon the functional and behavioral state of animals. It was found that the conventional therapeutic index does not coincide with the actual therapeutic activity range. Piracetam and picamilon, while exhibiting significantly different toxicity, are characterized by approximately equal ranges of the therapeutic activity.

Optimal Bandwidth Selection in Observed-Score Kernel Equating

ERIC Educational Resources Information Center

Häggström, Jenny; Wiberg, Marie

2014-01-01

The selection of bandwidth in kernel equating is important because it has a direct impact on the equated test scores. The aim of this article is to examine the use of double smoothing when selecting bandwidths in kernel equating and to compare double smoothing with the commonly used penalty method. This comparison was made using both an equivalent…

Detecting determinism with improved sensitivity in time series: rank-based nonlinear predictability score.

PubMed

Naro, Daniel; Rummel, Christian; Schindler, Kaspar; Andrzejak, Ralph G

2014-09-01

The rank-based nonlinear predictability score was recently introduced as a test for determinism in point processes. We here adapt this measure to time series sampled from time-continuous flows. We use noisy Lorenz signals to compare this approach against a classical amplitude-based nonlinear prediction error. Both measures show an almost identical robustness against Gaussian white noise. In contrast, when the amplitude distribution of the noise has a narrower central peak and heavier tails than the normal distribution, the rank-based nonlinear predictability score outperforms the amplitude-based nonlinear prediction error. For this type of noise, the nonlinear predictability score has a higher sensitivity for deterministic structure in noisy signals. It also yields a higher statistical power in a surrogate test of the null hypothesis of linear stochastic correlated signals. We show the high relevance of this improved performance in an application to electroencephalographic (EEG) recordings from epilepsy patients. Here the nonlinear predictability score again appears of higher sensitivity to nonrandomness. Importantly, it yields an improved contrast between signals recorded from brain areas where the first ictal EEG signal changes were detected (focal EEG signals) versus signals recorded from brain areas that were not involved at seizure onset (nonfocal EEG signals).

Detecting determinism with improved sensitivity in time series: Rank-based nonlinear predictability score

NASA Astrophysics Data System (ADS)

Naro, Daniel; Rummel, Christian; Schindler, Kaspar; Andrzejak, Ralph G.

2014-09-01

The rank-based nonlinear predictability score was recently introduced as a test for determinism in point processes. We here adapt this measure to time series sampled from time-continuous flows. We use noisy Lorenz signals to compare this approach against a classical amplitude-based nonlinear prediction error. Both measures show an almost identical robustness against Gaussian white noise. In contrast, when the amplitude distribution of the noise has a narrower central peak and heavier tails than the normal distribution, the rank-based nonlinear predictability score outperforms the amplitude-based nonlinear prediction error. For this type of noise, the nonlinear predictability score has a higher sensitivity for deterministic structure in noisy signals. It also yields a higher statistical power in a surrogate test of the null hypothesis of linear stochastic correlated signals. We show the high relevance of this improved performance in an application to electroencephalographic (EEG) recordings from epilepsy patients. Here the nonlinear predictability score again appears of higher sensitivity to nonrandomness. Importantly, it yields an improved contrast between signals recorded from brain areas where the first ictal EEG signal changes were detected (focal EEG signals) versus signals recorded from brain areas that were not involved at seizure onset (nonfocal EEG signals).

Reliable change indices and standardized regression-based change score norms for evaluating neuropsychological change in children with epilepsy.

PubMed

Busch, Robyn M; Lineweaver, Tara T; Ferguson, Lisa; Haut, Jennifer S

2015-06-01

Reliable change indices (RCIs) and standardized regression-based (SRB) change score norms permit evaluation of meaningful changes in test scores following treatment interventions, like epilepsy surgery, while accounting for test-retest reliability, practice effects, score fluctuations due to error, and relevant clinical and demographic factors. Although these methods are frequently used to assess cognitive change after epilepsy surgery in adults, they have not been widely applied to examine cognitive change in children with epilepsy. The goal of the current study was to develop RCIs and SRB change score norms for use in children with epilepsy. Sixty-three children with epilepsy (age range: 6-16; M=10.19, SD=2.58) underwent comprehensive neuropsychological evaluations at two time points an average of 12 months apart. Practice effect-adjusted RCIs and SRB change score norms were calculated for all cognitive measures in the battery. Practice effects were quite variable across the neuropsychological measures, with the greatest differences observed among older children, particularly on the Children's Memory Scale and Wisconsin Card Sorting Test. There was also notable variability in test-retest reliabilities across measures in the battery, with coefficients ranging from 0.14 to 0.92. Reliable change indices and SRB change score norms for use in assessing meaningful cognitive change in children following epilepsy surgery are provided for measures with reliability coefficients above 0.50. This is the first study to provide RCIs and SRB change score norms for a comprehensive neuropsychological battery based on a large sample of children with epilepsy. Tables to aid in evaluating cognitive changes in children who have undergone epilepsy surgery are provided for clinical use. An Excel sheet to perform all relevant calculations is also available to interested clinicians or researchers. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of a Food Group-Based Diet Score and Its Association with Bone Mineral Density in the Elderly: The Rotterdam Study

PubMed Central

de Jonge, Ester A. L.; Kiefte-de Jong, Jessica C.; de Groot, Lisette C. P. G. M.; Voortman, Trudy; Schoufour, Josje D.; Zillikens, M. Carola; Hofman, Albert; Uitterlinden, André G.; Franco, Oscar H.; Rivadeneira, Fernando

2015-01-01

No diet score exists that summarizes the features of a diet that is optimal for bone mineral density (BMD) in the elderly. Our aims were (a) to develop a BMD-Diet Score reflecting a diet that may be beneficial for BMD based on the existing literature, and (b) to examine the association of the BMD-Diet Score and the Healthy Diet Indicator, a score based on guidelines of the World Health Organization, with BMD in Dutch elderly participating in a prospective cohort study, the Rotterdam Study (n = 5144). Baseline dietary intake, assessed using a food frequency questionnaire, was categorized into food groups. Food groups that were consistently associated with BMD in the literature were included in the BMD-Diet Score. BMD was measured repeatedly and was assessed using dual energy X-ray absorptiometry. The BMD-Diet Score considered intake of vegetables, fruits, fish, whole grains, legumes/beans and dairy products as “high-BMD” components and meat and confectionary as “low-BMD” components. After adjustment, the BMD-Diet Score was positively associated with BMD (β (95% confidence interval) = 0.009 (0.005, 0.012) g/cm2 per standard deviation). This effect size was approximately three times as large as has been observed for the Healthy Diet Indicator. The food groups included in our BMD-Diet Score could be considered in the development of future dietary guidelines for healthy ageing. PMID:26295256

Reproducibility of the NEPTUNE descriptor-based scoring system on whole-slide images and histologic and ultrastructural digital images.

PubMed

Barisoni, Laura; Troost, Jonathan P; Nast, Cynthia; Bagnasco, Serena; Avila-Casado, Carmen; Hodgin, Jeffrey; Palmer, Matthew; Rosenberg, Avi; Gasim, Adil; Liensziewski, Chrysta; Merlino, Lino; Chien, Hui-Ping; Chang, Anthony; Meehan, Shane M; Gaut, Joseph; Song, Peter; Holzman, Lawrence; Gibson, Debbie; Kretzler, Matthias; Gillespie, Brenda W; Hewitt, Stephen M

2016-07-01

The multicenter Nephrotic Syndrome Study Network (NEPTUNE) digital pathology scoring system employs a novel and comprehensive methodology to document pathologic features from whole-slide images, immunofluorescence and ultrastructural digital images. To estimate inter- and intra-reader concordance of this descriptor-based approach, data from 12 pathologists (eight NEPTUNE and four non-NEPTUNE) with experience from training to 30 years were collected. A descriptor reference manual was generated and a webinar-based protocol for consensus/cross-training implemented. Intra-reader concordance for 51 glomerular descriptors was evaluated on jpeg images by seven NEPTUNE pathologists scoring 131 glomeruli three times (Tests I, II, and III), each test following a consensus webinar review. Inter-reader concordance of glomerular descriptors was evaluated in 315 glomeruli by all pathologists; interstitial fibrosis and tubular atrophy (244 cases, whole-slide images) and four ultrastructural podocyte descriptors (178 cases, jpeg images) were evaluated once by six and five pathologists, respectively. Cohen's kappa for inter-reader concordance for 48/51 glomerular descriptors with sufficient observations was moderate (0.40based on similar pathologic features improved concordance. Concordance was independent of years of experience, and increased with webinar cross-training. Excellent concordance was achieved for interstitial fibrosis and tubular atrophy. Moderate-to-excellent concordance was achieved for all ultrastructural podocyte descriptors, with good-to-excellent concordance for descriptors commonly used in clinical practice, foot process effacement, and microvillous transformation. NEPTUNE digital pathology scoring system enables novel morphologic profiling of renal structures. For all histologic and ultrastructural descriptors tested with

TOXICITY TESTS FOR SEDIMENT QUALITY ASSESSMENTS

EPA Science Inventory

Toxic sediments have contributed to a wide-variety of environmental problems around the world. The observed effects include direct toxic effects to aquatic life, bio-magnification of toxicants in the food chain, and economic impacts. This chapter discusses the use of toxicity...

Semiautomated Motility Assay For Determining Toxicity

NASA Technical Reports Server (NTRS)

Noever, David A.; Cronise, Raymond

1996-01-01

Improved method of assessing toxicities of various substances based on observation of effects of those substances on motilities of manageably small number of cells of protozoan species Tetrahema pyriformis. Provides repeatable, standardized tests with minimal handling by technicians and with minimal exposure of technicians to chemicals. Rapid and economical alternative to Draize test.

A simple scoring system based on neutrophil count in sepsis patients.

PubMed

Ueda, Takahiro; Aoyama-Ishikawa, Michiko; Nakao, Atsunori; Yamada, Taihei; Usami, Makoto; Kotani, Joji

2014-03-01

-survivors of sepsis and severe sepsis/septic shock (p<0.01, t-test) than in survivors. The ROC curve showed a sensitivity of 61.5% and a specificity of 80.4% at an n-score of 3.8 points; the area under the curve was 0.736. In addition, n-score correlated with APACHE II score (p<0.01, R=0.378) and SOFA score (p<0.05, R=0.256) on admission. Based on these preliminary evaluations, we hypothesize that n-score may be a useful scoring system to detect risk of death in sepsis and severe sepsis/septic shock. Copyright © 2014 Elsevier Ltd. All rights reserved.

Microbial Fuels Cell-Based Biosensor for Toxicity Detection: A Review

PubMed Central

Zhou, Tuoyu; Han, Huawen; Liu, Pu; Xiong, Jian; Tian, Fake; Li, Xiangkai

2017-01-01

With the unprecedented deterioration of environmental quality, rapid recognition of toxic compounds is paramount for performing in situ real-time monitoring. Although several analytical techniques based on electrochemistry or biosensors have been developed for the detection of toxic compounds, most of them are time-consuming, inaccurate, or cumbersome for practical applications. More recently, microbial fuel cell (MFC)-based biosensors have drawn increasing interest due to their sustainability and cost-effectiveness, with applications ranging from the monitoring of anaerobic digestion process parameters (VFA) to water quality detection (e.g., COD, BOD). When a MFC runs under correct conditions, the voltage generated is correlated with the amount of a given substrate. Based on this linear relationship, several studies have demonstrated that MFC-based biosensors could detect heavy metals such as copper, chromium, or zinc, as well as organic compounds, including p-nitrophenol (PNP), formaldehyde and levofloxacin. Both bacterial consortia and single strains can be used to develop MFC-based biosensors. Biosensors with single strains show several advantages over systems integrating bacterial consortia, such as selectivity and stability. One of the limitations of such sensors is that the detection range usually exceeds the actual pollution level. Therefore, improving their sensitivity is the most important for widespread application. Nonetheless, MFC-based biosensors represent a promising approach towards single pollutant detection. PMID:28956857

Microbial Fuels Cell-Based Biosensor for Toxicity Detection: A Review.

PubMed

Zhou, Tuoyu; Han, Huawen; Liu, Pu; Xiong, Jian; Tian, Fake; Li, Xiangkai

2017-09-28

With the unprecedented deterioration of environmental quality, rapid recognition of toxic compounds is paramount for performing in situ real-time monitoring. Although several analytical techniques based on electrochemistry or biosensors have been developed for the detection of toxic compounds, most of them are time-consuming, inaccurate, or cumbersome for practical applications. More recently, microbial fuel cell (MFC)-based biosensors have drawn increasing interest due to their sustainability and cost-effectiveness, with applications ranging from the monitoring of anaerobic digestion process parameters (VFA) to water quality detection (e.g., COD, BOD). When a MFC runs under correct conditions, the voltage generated is correlated with the amount of a given substrate. Based on this linear relationship, several studies have demonstrated that MFC-based biosensors could detect heavy metals such as copper, chromium, or zinc, as well as organic compounds, including p -nitrophenol (PNP), formaldehyde and levofloxacin. Both bacterial consortia and single strains can be used to develop MFC-based biosensors. Biosensors with single strains show several advantages over systems integrating bacterial consortia, such as selectivity and stability. One of the limitations of such sensors is that the detection range usually exceeds the actual pollution level. Therefore, improving their sensitivity is the most important for widespread application. Nonetheless, MFC-based biosensors represent a promising approach towards single pollutant detection.

Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data

EPA Science Inventory

EPA's ToxCast™ project is profiling the in vitro bioactivity of chemicals to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesized that developmental toxicity in guideline animal studies captured in the ToxRefDB database wou...

Methods of Implementation of Evidence-Based Stroke Care in Europe: European Implementation Score Collaboration.

PubMed

Di Carlo, Antonio; Pezzella, Francesca Romana; Fraser, Alec; Bovis, Francesca; Baeza, Juan; McKevitt, Chris; Boaz, Annette; Heuschmann, Peter; Wolfe, Charles D A; Inzitari, Domenico

2015-08-01

Differences in stroke care and outcomes reported in Europe may reflect different degrees of implementation of evidence-based interventions. We evaluated strategies for implementing research evidence into stroke care in 10 European countries. A questionnaire was developed and administered through face-to-face interviews with key informants. Implementation strategies were investigated considering 3 levels (macro, meso, and micro, eg, policy, organization, patients/professionals) identified by the framing analysis, and different settings (primary, hospital, and specialist) of stroke care. Similarities and differences among countries were evaluated using the categorical principal components analysis. Implementation methods reported by ≥7 countries included nonmandatory policies, public financial incentives, continuing professional education, distribution of educational material, educational meetings and campaigns, guidelines, opinion leaders', and stroke patients associations' activities. Audits were present in 6 countries at national level; national and regional regulations in 4 countries. Private financial incentives, reminders, and educational outreach visits were reported only in 2 countries. At national level, the first principal component of categorical principal components analysis separated England, France, Scotland, and Sweden, all with positive object scores, from the other countries. Belgium and Lithuania obtained the lowest scores. At regional level, England, France, Germany, Italy, and Sweden had positive scores in the first principal component, whereas Belgium, Lithuania, Poland, and Scotland showed negative scores. Spain was in an intermediate position. We developed a novel method to assess different domains of implementation in stroke care. Clear variations were observed among European countries. The new tool may be used elsewhere for future contributions. © 2015 American Heart Association, Inc.

Comparison of Toxicities to Vibrio fischeri and Fish Based on Discrimination of Excess Toxicity from Baseline Level

PubMed Central

Wang, Xiao H.; Yu, Yang; Huang, Tao; Qin, Wei C.; Su, Li M.; Zhao, Yuan H.

2016-01-01

Investigations on the relationship of toxicities between species play an important role in the understanding of toxic mechanisms to environmental organisms. In this paper, the toxicity data of 949 chemicals to fish and 1470 chemicals to V. fischeri were used to investigate the modes of action (MOAs) between species. The results show that although there is a positive interspecies correlation, the relationship is poor. Analysis on the excess toxicity calculated from toxic ratios (TR) shows that many chemicals have close toxicities and share the same MOAs between the two species. Linear relationships between the toxicities and octanol/water partition coefficient (log KOW) for baseline and less inert compounds indicate that the internal critical concentrations (CBRs) approach a constant both to fish and V. fischeri for neutral hydrophobic compounds. These compounds share the same toxic mechanisms and bio-uptake processes between species. On the other hand, some hydrophilic compounds exhibit different toxic effects with greatly different log TR values between V. fischeri and fish species. These hydrophilic compounds were identified as reactive MOAs to V. fischeri, but not to fish. The interspecies correlation is improved by adding a hydrophobic descriptor into the correlation equation. This indicates that the differences in the toxic ratios between fish and V. fischeri for these hydrophilic compounds can be partly attributed to the differences of bioconcentration between the two species, rather than the differences of reactivity with the target macromolecules. These hydrophilic compounds may more easily pass through the cell membrane of V. fischeri than the gill and skin of fish, react with the target macromolecules and exhibit excess toxicity. The compounds with log KOW > 7 exhibiting very low toxicity (log TR < –1) to both species indicate that the bioconcentration potential of a chemical plays a very important role in the identification of excess toxicity and MOAs

Predictors of Liver Toxicity Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

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

Velec, Michael; Haddad, Carol R.; Craig, Tim

Purpose: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. Methods and Materials: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression. CP class B patients were analyzed separately. Results: Among CP class A patients, 101 were evaluable, with a baseline score of A5 (72%) or A6 (28%).more » Fifty-three percent had portal vein thrombus. The median liver volume was 1286 cc (range, 766-3967 cc), and the median prescribed dose was 36 Gy (range, 27-54 Gy). Toxicity was seen in 26 patients (26%). Thrombus, baseline CP of A6, and lower platelet count were associated with toxicity on univariate analysis, as were several liver DVH-based parameters. Absolute and spared liver volumes were not significant. On multivariate analysis for CP class A patients, significant associations were found for baseline CP score of A6 (odds ratio [OR], 4.85), lower platelet count (OR, 0.90; median, 108 × 10{sup 9}/L vs 150 × 10{sup 9}/L), higher mean liver dose (OR, 1.33; median, 16.9 Gy vs 14.7 Gy), and higher dose to 800 cc of liver (OR, 1.11; median, 14.3 Gy vs 6.0 Gy). With 13 CP-B7 patients included or when dose to 800 cc of liver was replaced with other DVH parameters (eg, dose to 700 or 900 cc of liver) in the multivariate analysis, effective volume and portal vein thrombus were associated with an increased risk. Conclusions: Baseline CP scores and higher liver doses (eg, mean dose, effective volume, doses to 700-900 cc) were strongly associated with liver function decline 3 months after SBRT. A lower baseline platelet count and portal vein thrombus were also associated

Radiography-based score indicative for the pathogenicity of bacteria in odontogenic infections.

PubMed

Cachovan, Georg; Blessmann, Marco; Schön, Gerhard; Rother, Uwe; Heiland, Max; Stürenburg, Enno; Platzer, Ursula; Sobottka, Ingo

2014-10-01

To develop a new radiography-based score to assess the potential of bacteria to cause odontogenic infections derived from the occurrence of bacteria at small or large radiographical lesions. The patients analyzed were a sub-population from a large randomized clinical trial comparing moxifloxacin and clindamycin in the treatment of inflammatory infiltrates and odontogenic abscesses. Routine radiographs were used to analyze the area of the periapical radiolucent lesions. Lesions were stratified by their radiographically measured area as large (>9 mm(2)) or small (≤9 mm(2)). A risk ratio was calculated for each species from the frequency of their occurrence in large vs in small lesions. Fifty-one patients, 19 with abscesses and 32 with infiltrates, were evaluated. Overall, the radiographical lesion areas ranged from 0.4-46.2 mm(2) (median = 9 mm(2)). An increased risk (risk ratio >1) to occur at large abscess lesions was observed for Prevotella (P.) oralis, P. buccae, P. oris, P. intermedia, Fusobacterium nucleatum and Streptococcus (Strep.) anginosus group. An increased risk to occur at large infiltrate lesions was found for Strep. salivarius, Strep. parasanguis, Strep. anginosus group, Capnocytophaga spp., Neisseria (N.) sicca, Neisseria spp., Staphylococcus (Staph.) aureus, P. intermedia, P. buccae, Prevotella spp. and P. melaninogenica. The radiography-based score suggests that certain Prevotella spp., F. nucleatum and Strep. anginosus groups play a crucial role in the pathogenesis of odontogenic abscesses, and that various streptococci, Neisseria spp., Capnocytophaga spp., Staph. aureus and Prevotella spp. are involved in the pathogenesis of odontogenic infiltrates.

Nutritional prognostic scores in patients with hilar cholangiocarcinoma treated by percutaneous transhepatic biliary stenting combined with 125I seed intracavitary irradiation: A retrospective observational study.

PubMed

Cui, Peiyuan; Pang, Qing; Wang, Yong; Qian, Zhen; Hu, Xiaosi; Wang, Wei; Li, Zongkuang; Zhou, Lei; Man, Zhongran; Yang, Song; Jin, Hao; Liu, Huichun

2018-06-01

We mainly aimed to preliminarily explore the prognostic values of nutrition-based prognostic scores in patients with advanced hilar cholangiocarcinoma (HCCA).We retrospectively analyzed 73 cases of HCCA, who underwent percutaneous transhepatic biliary stenting (PTBS) combined with I seed intracavitary irradiation from November 2012 to April 2017 in our department. The postoperative changes of total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and albumin (ALB) were observed. The preoperative clinical data were collected to calculate the nutrition-based scores, including controlling nutritional status (CONUT), C-reactive protein/albumin ratio (CAR), and prognostic nutritional index (PNI). Kaplan-Meier curve and Cox regression model were used for overall survival (OS) analyses.The serum levels of TBIL, DBIL, ALT, AST, and ALP significantly reduced, and ALB significantly increased at 1 month and 3 months postoperatively. The median survival time of the cohort was 12 months and the 1-year survival rate was 53.1%. Univariate analysis revealed that the statistically significant factors related to OS were CA19-9, TBIL, ALB, CONUT, and PNI. Multivariate analysis further identified CA19-9, CONUT, and PNI as independent prognostic factors.Nutrition-based prognostic scores, CONUT and PNI in particular, can be used as predictors of survival in unresectable HCCA.

Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing.

PubMed

Hu, Li-Xin; Ying, Guang-Guo; Chen, Xiao-Wen; Huang, Guo-Yong; Liu, You-Sheng; Jiang, Yu-Xia; Pan, Chang-Gui; Tian, Fei; Martin, Francis L

2017-02-01

Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346-353. © 2016 SETAC. © 2016 SETAC.

Robust LOD scores for variance component-based linkage analysis.

PubMed

Blangero, J; Williams, J T; Almasy, L

2000-01-01

The variance component method is now widely used for linkage analysis of quantitative traits. Although this approach offers many advantages, the importance of the underlying assumption of multivariate normality of the trait distribution within pedigrees has not been studied extensively. Simulation studies have shown that traits with leptokurtic distributions yield linkage test statistics that exhibit excessive Type I error when analyzed naively. We derive analytical formulae relating the deviation from the expected asymptotic distribution of the lod score to the kurtosis and total heritability of the quantitative trait. A simple correction constant yields a robust lod score for any deviation from normality and for any pedigree structure, and effectively eliminates the problem of inflated Type I error due to misspecification of the underlying probability model in variance component-based linkage analysis.

Assessment of Jatropha curcas L. biodiesel seed cake toxicity using the zebrafish (Danio rerio) embryo toxicity (ZFET) test.

PubMed

Hallare, Arnold V; Ruiz, Paulo Lorenzo S; Cariño, J C Earl D

2014-05-01

Consequent to the growing demand for alternative sources of energy, the seeds from Jatropha curcas remain to be the favorite for biodiesel production. However, a significant volume of the residual organic mass (seed cake) is produced during the extraction process, which raises concerns on safe waste disposal. In the present study, we assessed the toxicity of J. curcas seed cake using the zebrafish (Danio rerio) embryotoxicity test. Within 1-h post-fertilization (hpf), the fertilized eggs were exposed to five mass concentrations of J. curcas seed cake and were followed through 24, 48, and 72 hpf. Toxicity was evaluated based on lethal endpoints induced on zebrafish embryos namely egg coagulation, non-formation of somites, and non-detachment of tail. The lowest concentration tested, 1 g/L, was not able to elicit toxicity on embryos whereas 100 % mortality (based also on lethal endpoints) was recorded at the highest concentration at 2.15 g/L. The computed LC50 for the J. curcas seed cake was 1.61 g/L. No further increase in mortality was observed in the succeeding time points (48 and 72 hpf) indicating that J. curcas seed cake exerted acute toxicity on zebrafish embryos. Sublethal endpoints (yolk sac and pericardial edema) were noted at 72 hpf in zebrafish embryos exposed to higher concentrations. The observed lethal endpoints induced on zebrafish embryos were discussed in relation to the active principles, notably, phorbol esters that have remained in the seed cake even after extraction.

A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score

PubMed Central

Hijazi, Ziad; Oldgren, Jonas; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Yusuf, Salim; Granger, Christopher B; Siegbahn, Agneta; Wallentin, Lars

2018-01-01

Abstract Aims In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers. Methods and results The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score. Conclusion A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF. ClinicalTrials.gov identifier NCT00412984 and NCT00262600 PMID:29069359

Soil microbial toxicity assessment of a copper-based fungicide in two contrasting soils

NASA Astrophysics Data System (ADS)

Dober, Melanie; Deltedesco, Evi; Jöchlinger, Lisa; Schneider, Martin; Gorfer, Markus; Bruckner, Alexander; Zechmeister-Boltenstern, Sophie; Soja, Gerhard; Zehetner, Franz; Keiblinger, Katharina Maria

2016-04-01

The infestation with the fungus downy mildew (Plasmopara viticola) causes dramatic losses in wine production. Copper (Cu) based fungicides have been used in viticulture since the end of the 19th century, and until today both conventional and organic viticulture strongly rely on Cu to prevent and reduce fungal diseases. Consequently, Cu has built up in many vineyard soils and it is still unclear how this affects soil functioning. The aim of the present study is the evaluation of the soil microbial toxicity of Cu contamination. Two contrasting agricultural soils, an acidic sandy soil and a calcareous loamy soil, were sampled to conduct an eco-toxicological greenhouse pot experiment. The soils were spiked with a commonly used fungicide based on copper hydroxid in seven concentrations (0, 50, 100, 200, 500, 1500 and 5000 mg Cu kg-1 soil) and Lucerne (Medicago sativa L. cultivar. Plato) was grown in the pots for 3 months. Sampling was conducted at the beginning and at the end of the study period to test copper's soil microbial toxicity in total microbial biomass and basal respiration, as well as enzyme activities, such as exoglucanase, β-glucosidase, exochitinase, phosphatase, protease, phenol-, peroxidase and urease. Additionally, DOC, TN, Cmic, Nmic, NO3 and NH4 were determined to provide further insight into the carbon and nitrogen cycle. Microbial community structure was analysed by phospholipid fatty acids (PLFAs), and ergosterol as a fungal biomarker. In addition, molecular tools were applied by extracting soil DNA and performing real time quantitative polymerase chain reaction (qPCR) and a metagenomic approach using 16S and ITS amplification and sequencing with MiSeq platform for the second sampling. Hydrolytic extracellular enzymes were not clearly affected by rising Cu concentrations, while a trend of increasing activity of oxidative enzymes (phenol- and peroxidase) was observed. Microbial respiration rate as well as the amount of Cmic and Nmic decreased with

Comparing probabilistic and descriptive analyses of time–dose–toxicity relationship for determining no-observed-adverse-effect level in drug development

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

Glatard, Anaïs; Berges, Aliénor; Sahota, Tarjinder

The no-observed-adverse-effect level (NOAEL) of a drug defined from animal studies is important for inferring a maximal safe dose in human. However, several issues are associated with its concept, determination and application. It is confined to the actual doses used in the study; becomes lower with increasing sample size or dose levels; and reflects the risk level seen in the experiment rather than what may be relevant for human. We explored a pharmacometric approach in an attempt to address these issues. We first used simulation to examine the behaviour of the NOAEL values as determined by current common practice; andmore » then fitted the probability of toxicity as a function of treatment duration and dose to data collected from all applicable toxicology studies of a test compound. Our investigation was in the context of an irreversible toxicity that is detected at the end of the study. Simulations illustrated NOAEL's dependency on experimental factors such as dose and sample size, as well as the underlying uncertainty. Modelling the probability as a continuous function of treatment duration and dose simultaneously to data from multiple studies allowed the estimation of the dose, along with its confidence interval, for a maximal risk level that might be deemed as acceptable for human. The model-based data integration also reconciled between-study inconsistency and explicitly provided maximised estimation confidence. Such alternative NOAEL determination method should be explored for its more efficient data use, more quantifiable insight to toxic doses, and the potential for more relevant animal-to-human translation. - Highlights: • Simulations revealed issues with NOAEL concept, determination and application. • Probabilistic modelling was used to address these issues. • The model integrated time-dose-toxicity data from multiple studies. • The approach uses data efficiently and may allow more meaningful human translation.« less

Foundations of Observation: Considerations for Developing a Classroom Observation System That Helps Districts Achieve Consistent and Accurate Scores. MET Project, Policy and Practice Brief

ERIC Educational Resources Information Center

Joe, Jilliam N.; Tocci, Cynthia M.; Holtzman, Steven L.; Williams, Jean C.

2013-01-01

The purpose of this paper is to provide states and school districts with processes they can use to help ensure high-quality data collection during teacher observations. Educational Testing Service's (ETS's) goal in writing it is to share the knowledge and expertise they gained: (1) from designing and implementing scoring processes for the Measures…

Wildlife toxicity extrapolations: NOAEL versus LOAEL

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

Fairbrother, A.; Berg, M. van den

1995-12-31

Ecotoxicological assessments must rely on the extrapolation of toxicity data from a few indicator species to many species of concern. Data are available from laboratory studies (e.g., quail, mallards, rainbow trout, fathead minnow) and some planned or serendipitous field studies of a broader, but by no means comprehensive, suite of species. Yet all ecological risk assessments begin with an estimate of risk based on information gleaned from the literature. One is then confronted with the necessity of extrapolating toxicity information from a limited number of indicator species to all organisms of interest. This is a particularly acute problem when tryingmore » to estimate hazards to wildlife in terrestrial systems as there is an extreme paucity of data for most chemicals in all but a handful of species. This section continues the debate by six panelists of the ``correct`` approach for determining wildlife toxicity thresholds by debating which toxicity value should be used for setting threshold criteria. Should the lowest observable effect level (LOAEL) be used or is it more appropriate to use the no observable effect level (NOAEL)? What are the short-comings of using either of these point estimates? Should a ``benchmark`` approach, similar to that proposed for human health risk assessments, be used instead, where an EC{sub 5} or EC{sub 10} and associated confidence limits are determined and then divided by a safety factor? How should knowledge of the slope of the dose-response curve be incorporated into determination of toxicity threshold values?« less

Higher blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations correlate with lower olfactory scores in essential tremor.

PubMed

Louis, Elan D; Rios, Eileen; Pellegrino, Kathryn M; Jiang, Wendy; Factor-Litvak, Pam; Zheng, Wei

2008-05-01

Harmane (1-methyl-9H-pyrido[3,4-b]indole), a neurotoxin, may be an environmental risk factor for essential tremor (ET). Harmane and related chemicals are toxic to the cerebellum. Whether it is through this mechanism (cerebellar toxicity) that harmane leads to ET is unknown. Impaired olfaction may be a feature of cerebellar disease. To determine whether blood harmane concentrations correlate with olfactory test scores in patients with ET. Blood harmane concentrations were quantified using high performance liquid chromatography. Odor identification testing was performed with the University of Pennsylvania Smell Identification Test (UPSIT). In 83 ET cases, higher log blood harmane concentration was correlated with lower UPSIT score (rho=-0.46, p<0.001). 25/40 (62.5%) cases with high log blood harmane concentration (based on a median split) had low UPSIT scores (based on a median split) vs. 12/43 (27.9%) ET cases with low log blood harmane concentration (adjusted odd ratios (OR) 4.04, 95% confidence intervals (CI) 1.42-11.50, p=0.009). When compared with the low log blood harmane tertile, the odds of olfactory dysfunction were 2.64 times higher in cases in the middle tertile and 10.95 times higher in cases in the high tertile. In 69 control subjects, higher log blood harmane concentration was not correlated with lower UPSIT score (rho=0.12, p=0.32). Blood harmane concentrations were correlated with UPSIT scores in ET cases but not controls. These analyses set the stage for postmortem studies to further explore the role of harmane as a cerebellar toxin in ET.

Glasgow prognostic score is superior to other inflammation-based scores in predicting survival of diffuse large B-cell lymphoma

PubMed Central

Wei, Xiaolei; Zhou, Lizhi; Wei, Qi; Zhang, Yuankun; Huang, Weimin; Feng, Ru

2017-01-01

Inflammation-based prognostic scores, such as the glasgow prognostic score (GPS), prognostic index (PI), prognostic nutritional index (PNI), neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were related to survival in many solid tumors. Recent study showed that GPS can be used to predict outcome in diffuse large B-cell lymphoma (DLBCL). However, other inflammation related scores had not been reported and it also remained unknown which of them was the most useful to evaluate the survival in DLBCLs. In this retrospective study, a number of 252 newly diagnosed and histologically proven DLBCLs from January 2003 to December 2014 were included. The high GPS, high PI, high NLR, high PLR and low PNI were all associated with poor overall survival (p < 0.05) and event-free survival (p < 0.05) in univariate analysis. Multivariate analysis indicated that GPS (HR = 1.781, 95% CI = 1.065–2.979, p = 0.028) remained an independent prognostic predictor in DLBCL. The c-index of GPS (0.735, 95% CI = 0.645–0.824) was greater than that of PI (0.710, 95% CI = 0.621–0.799, p = 0.602), PNI (0.600, 95% CI = 0.517–0.683, p = 0.001), PLR (0.599, 95% CI = 0.510–0.689, p = 0.029) and NLR (0.572, 95% CI = 0.503–0.642, p = 0.005) by Harrell's concordance index. Especially in DLBCLs treated with R-CHOP, GPS still remained the most powerful prognostic score when comparing with others (p = 0.001 and p < 0.001, respectively for OS and EFS). In conclusion, it is indicated that inflammation-based prognostic scores such as GPS, PI, NLR, PNI and PLR all could be used to predict the outcome of DLBCLs. Among them, GPS is the most powerful indicator in predicting survival in DLBCLs, even in the rituximab era. PMID:29100345

Open-Source Logic-Based Automated Sleep Scoring Software using Electrophysiological Recordings in Rats

PubMed Central

Gross, Brooks A.; Walsh, Christine M.; Turakhia, Apurva A.; Booth, Victoria; Mashour, George; Poe, Gina R.

2009-01-01

Manual state scoring of physiological recordings in sleep studies is time-consuming, resulting in a data backlog, research delays and increased personnel costs. We developed MATLAB-based software to automate scoring of sleep/waking states in rats, potentially extendable to other animals, from a variety of recording systems. The software contains two programs, Sleep Scorer and Auto-Scorer, for manual and automated scoring. Auto-Scorer is a logic-based program that displays power spectral densities of an electromyographic signal and σ, δ, and θ frequency bands of an electroencephalographic signal, along with the δ/θ ratio and σ ×θ, for every epoch. The user defines thresholds from the training file state definitions which the Auto-Scorer uses with logic to discriminate the state of every epoch in the file. Auto-Scorer was evaluated by comparing its output to manually scored files from 6 rats under 2 experimental conditions by 3 users. Each user generated a training file, set thresholds, and autoscored the 12 files into 4 states (waking, non-REM, transition-to-REM, and REM sleep) in ¼ the time required to manually score the file. Overall performance comparisons between Auto-Scorer and manual scoring resulted in a mean agreement of 80.24 +/− 7.87%, comparable to the average agreement among 3 manual scorers (83.03 +/− 4.00%). There was no significant difference between user-user and user-Auto-Scorer agreement ratios. These results support the use of our open-source Auto-Scorer, coupled with user review, to rapidly and accurately score sleep/waking states from rat recordings. PMID:19615408

Quality-of-Life Impairments Persist Six Months After Treatment of Graves' Hyperthyroidism and Toxic Nodular Goiter: A Prospective Cohort Study.

PubMed

Cramon, Per; Winther, Kristian Hillert; Watt, Torquil; Bonnema, Steen Joop; Bjorner, Jakob Bue; Ekholm, Ola; Groenvold, Mogens; Hegedüs, Laszlo; Feldt-Rasmussen, Ulla; Rasmussen, Åse Krogh

2016-08-01

The treatment of hyperthyroidism is aimed at improving health-related quality of life (HRQoL) and reducing morbidity and mortality. However, few studies have used validated questionnaires to assess HRQoL prospectively in such patients. The purpose of this study was to assess the impact of hyperthyroidism and its treatment on HRQoL using validated disease-specific and generic questionnaires. This prospective cohort study enrolled 88 patients with Graves' hyperthyroidism and 68 with toxic nodular goiter from endocrine outpatient clinics at two Danish university hospitals. The patients were treated with antithyroid drugs, radioactive iodine, or surgery. Disease-specific and generic HRQoL were assessed using the thyroid-related patient-reported outcome (ThyPRO) and the Medical Outcomes Study 36-item Short Form (SF-36), respectively, evaluated at baseline and six-month follow-up. The scores were compared with those from two general population samples who completed ThyPRO (n = 739) and SF-36 (n = 6638). Baseline scores for patients with Graves' hyperthyroidism and toxic nodular goiter were significantly worse than those for the general population scores on all comparable ThyPRO scales and all SF-36 scales and component summaries. ThyPRO scores improved significantly with treatment on all scales in Graves' hyperthyroidism and four scales in toxic nodular goiter, while SF-36 scores improved on five scales and both component summaries in Graves' hyperthyroidism and only one scale in toxic nodular goiter. In Graves' hyperthyroidism, large treatment effects were observed on three ThyPRO scales (Hyperthyroid Symptoms, Tiredness, Overall HRQoL) and moderate effects on three scales (Anxiety, Emotional Susceptibility, Impaired Daily Life), while moderate effects were seen in two ThyPRO scales in toxic nodular goiter (Anxiety, Overall HRQoL). However, significant disease-specific and generic HRQoL deficits persisted on multiple domains across both patient groups. Graves

Survival analysis using inverse probability of treatment weighted methods based on the generalized propensity score.

PubMed

Sugihara, Masahiro

2010-01-01

In survival analysis, treatment effects are commonly evaluated based on survival curves and hazard ratios as causal treatment effects. In observational studies, these estimates may be biased due to confounding factors. The inverse probability of treatment weighted (IPTW) method based on the propensity score is one of the approaches utilized to adjust for confounding factors between binary treatment groups. As a generalization of this methodology, we developed an exact formula for an IPTW log-rank test based on the generalized propensity score for survival data. This makes it possible to compare the group differences of IPTW Kaplan-Meier estimators of survival curves using an IPTW log-rank test for multi-valued treatments. As causal treatment effects, the hazard ratio can be estimated using the IPTW approach. If the treatments correspond to ordered levels of a treatment, the proposed method can be easily extended to the analysis of treatment effect patterns with contrast statistics. In this paper, the proposed method is illustrated with data from the Kyushu Lipid Intervention Study (KLIS), which investigated the primary preventive effects of pravastatin on coronary heart disease (CHD). The results of the proposed method suggested that pravastatin treatment reduces the risk of CHD and that compliance to pravastatin treatment is important for the prevention of CHD. (c) 2009 John Wiley & Sons, Ltd.

In silico toxicity prediction by support vector machine and SMILES representation-based string kernel.

PubMed

Cao, D-S; Zhao, J-C; Yang, Y-N; Zhao, C-X; Yan, J; Liu, S; Hu, Q-N; Xu, Q-S; Liang, Y-Z

2012-01-01

There is a great need to assess the harmful effects or toxicities of chemicals to which man is exposed. In the present paper, the simplified molecular input line entry specification (SMILES) representation-based string kernel, together with the state-of-the-art support vector machine (SVM) algorithm, were used to classify the toxicity of chemicals from the US Environmental Protection Agency Distributed Structure-Searchable Toxicity (DSSTox) database network. In this method, the molecular structure can be directly encoded by a series of SMILES substrings that represent the presence of some chemical elements and different kinds of chemical bonds (double, triple and stereochemistry) in the molecules. Thus, SMILES string kernel can accurately and directly measure the similarities of molecules by a series of local information hidden in the molecules. Two model validation approaches, five-fold cross-validation and independent validation set, were used for assessing the predictive capability of our developed models. The results obtained indicate that SVM based on the SMILES string kernel can be regarded as a very promising and alternative modelling approach for potential toxicity prediction of chemicals.

Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation

PubMed Central

Wu, Chia-Chou; Lin, Che

2015-01-01

The induction of stem cells toward a desired differentiation direction is required for the advancement of stem cell-based therapies. Despite successful demonstrations of the control of differentiation direction, the effective use of stem cell-based therapies suffers from a lack of systematic knowledge regarding the mechanisms underlying directed differentiation. Using dynamic modeling and the temporal microarray data of three differentiation stages, three dynamic protein-protein interaction networks were constructed. The interaction difference networks derived from the constructed networks systematically delineated the evolution of interaction variations and the underlying mechanisms. A proposed relevance score identified the essential components in the directed differentiation. Inspection of well-known proteins and functional modules in the directed differentiation showed the plausibility of the proposed relevance score, with the higher scores of several proteins and function modules indicating their essential roles in the directed differentiation. During the differentiation process, the proteins and functional modules with higher relevance scores also became more specific to the neuronal identity. Ultimately, the essential components revealed by the relevance scores may play a role in controlling the direction of differentiation. In addition, these components may serve as a starting point for understanding the systematic mechanisms of directed differentiation and for increasing the efficiency of stem cell-based therapies. PMID:25977693

Are the Best Scores the Best Scores for Predicting College Success?

ERIC Educational Resources Information Center

Patterson, Brian F.; Mattern, Krista D.; Swerdzewski, Peter

2012-01-01

The College Board's SAT[R] Score Choice[TM] policy allows students to choose which set(s) of scores to send to colleges and universities to which they plan to apply. Based on data gathered before the implementation of that policy, the following study evaluated the predictive validity of the various sets of SAT scores. The value of five score sets…

Tox21 Enricher: Web-based Chemical/Biological Functional Annotation Analysis Tool Based on Tox21 Toxicity Screening Platform.

PubMed

Hur, Junguk; Danes, Larson; Hsieh, Jui-Hua; McGregor, Brett; Krout, Dakota; Auerbach, Scott

2018-05-01

The US Toxicology Testing in the 21st Century (Tox21) program was established to develop more efficient and human-relevant toxicity assessment methods. The Tox21 program screens >10,000 chemicals using quantitative high-throughput screening (qHTS) of assays that measure effects on toxicity pathways. To date, more than 70 assays have yielded >12 million concentration-response curves. The patterns of activity across assays can be used to define similarity between chemicals. Assuming chemicals with similar activity profiles have similar toxicological properties, we may infer toxicological properties based on its neighbourhood. One approach to inference is chemical/biological annotation enrichment analysis. Here, we present Tox21 Enricher, a web-based chemical annotation enrichment tool for the Tox21 toxicity screening platform. Tox21 Enricher identifies over-represented chemical/biological annotations among lists of chemicals (neighbourhoods), facilitating the identification of the toxicological properties and mechanisms in the chemical set. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

New Equating Methods and Their Relationships with Levine Observed Score Linear Equating under the Kernel Equating Framework

ERIC Educational Resources Information Center

Chen, Haiwen; Holland, Paul

2010-01-01

In this paper, we develop a new curvilinear equating for the nonequivalent groups with anchor test (NEAT) design under the assumption of the classical test theory model, that we name curvilinear Levine observed score equating. In fact, by applying both the kernel equating framework and the mean preserving linear transformation of…

Measurement Properties of the Smartphone-Based B-B Score in Current Shoulder Pathologies

PubMed Central

Pichonnaz, Claude; Duc, Cyntia; Gleeson, Nigel; Ancey, Céline; Jaccard, Hervé; Lécureux, Estelle; Farron, Alain; Jolles, Brigitte M.; Aminian, Kamiar

2015-01-01

This study is aimed at the determination of the measurement properties of the shoulder function B-B Score measured with a smartphone. This score measures the symmetry between sides of a power-related metric for two selected movements, with 100% representing perfect symmetry. Twenty healthy participants, 20 patients with rotator cuff conditions, 23 with fractures, 22 with capsulitis, and 23 with shoulder instabilities were measured twice across a six-month interval using the B-B Score and shoulder function questionnaires. The discriminative power, responsiveness, diagnostic power, concurrent validity, minimal detectable change (MDC), minimal clinically important improvement (MCII), and patient acceptable symptom state (PASS) were evaluated. Significant differences with the control group and significant baseline—six-month differences were found for the rotator cuff condition, fracture, and capsulitis patient groups. The B-B Score was responsive and demonstrated excellent diagnostic power, except for shoulder instability. The correlations with clinical scores were generally moderate to high, but lower for instability. The MDC was 18.1%, the MCII was 25.2%, and the PASS was 77.6. No floor effect was observed. The B-B Score demonstrated excellent measurement properties in populations with rotator cuff conditions, proximal humerus fractures, and capsulitis, and can thus be used as a routine test to evaluate those patients. PMID:26506355

Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer.

PubMed

Ramsey, Sara; Lamb, Gavin W A; Aitchison, Michael; Graham, John; McMillan, Donald C

2007-01-15

Recently, it was shown that an inflammation-based prognostic score, the Glasgow Prognostic Score (GPS), provides additional prognostic information in patients with advanced cancer. The objective of the current study was to examine the value of the GPS compared with established scoring systems in predicting cancer-specific survival in patients with metastatic renal cancer. One hundred nineteen patients who underwent immunotherapy for metastatic renal cancer were recruited. The Memorial Sloan-Kettering Cancer Center (MSKCC) score and the Metastatic Renal Carcinoma Comprehensive Prognostic System (MRCCPS) score were calculated as described previously. Patients who had both an elevated C-reactive protein level (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients who had only 1 of those 2 biochemical abnormalities were allocated a GPS of 1. Patients who had neither abnormality were allocated a GPS of 0. On multivariate analysis of significant individual factors, only calcium (hazard ratio [HR], 3.21; 95% confidence interval [95% CI], 1.51-6.83; P = .002), white cell count (HR, 1.66; 95% CI, 1.17-2.35; P = .004), albumin (HR, 2.63; 95% CI, 1.38-5.03; P = .003), and C-reactive protein (HR, 2.85; 95% CI; 1.49-5.45; P = .002) were associated independently with cancer-specific survival. On multivariate analysis of the different scoring systems, the MSKCC (HR, 1.88; 95% CI, 1.22-2.88; P = .004), the MRCCPS (HR, 1.42; 95% CI, 0.97-2.09; P = .071), and the GPS (HR, 2.35; 95% CI, 1.51-3.67; P < .001) were associated independently with cancer-specific survival. An inflammation-based prognostic score (GPS) predicted survival independent of established scoring systems in patients with metastatic renal cancer.

A Step-by-Step Guide to Propensity Score Matching in R

ERIC Educational Resources Information Center

Randolph, Justus J.; Falbe, Kristina; Manuel, Austin Kureethara; Balloun, Joseph L.

2014-01-01

Propensity score matching is a statistical technique in which a treatment case is matched with one or more control cases based on each case's propensity score. This matching can help strengthen causal arguments in quasi-experimental and observational studies by reducing selection bias. In this article we concentrate on how to conduct propensity…

System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses

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

Snyder-Talkington, Brandi N.; Dymacek, Julian; Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300

2013-10-15

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 μg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chainmore » simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. - Highlights: • A novel computational model identified toxicity pathways matching in vivo pathology. • Systematic identification of MWCNT-induced biological processes in mouse lungs • MWCNT-induced functional networks of

FETAX assay for evaluation of developmental toxicity.

PubMed

Mouche, Isabelle; Malesic, Laure; Gillardeaux, Olivier

2011-01-01

The Frog Embryo Teratogenesis Assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larva. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.

FETAX Assay for Evaluation of Developmental Toxicity.

PubMed

Mouche, Isabelle; Malésic, Laure; Gillardeaux, Olivier

2017-01-01

The frog embryo teratogenesis assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula-stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larvae. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.

Toxicity of atrazine- and glyphosate-based formulations on Caenorhabditis elegans.

PubMed

García-Espiñeira, María; Tejeda-Benitez, Lesly; Olivero-Verbel, Jesus

2018-07-30

Atrazine and Glyphosate are herbicides massively used in agriculture for crop protection. Upon application, they are available to the biota in different ecosystems. The aim of this research was to evaluate the toxicity of Glyphosate and Atrazine based formulations (GBF and ABF, respectively). Caenorhabditis elegans was exposed to different concentrations of each single formulation, and to the mixture. Lethality, locomotion, growth, and fertility were measured as endpoints. Effects on gene expression were monitored utilizing green fluorescence protein transgenic strains. ABF caused lethality of 12%, 15%, and 18% for 6, 60, and 600 μM, respectively, displaying a dose dependence trend. GBF produced lethality of 20%, 50%, and 100% at 0.01, 10, and 100 μM, respectively. Locomotion inhibition ranged from 21% to 89% at the lowest and maximum tested concentrations for Atrazine; whereas for Glyphosate, exposure to 10 μM inhibited 87%. Brood size was decreased by 67% and 93% after treatment to 0.06 and 6 μM Atrazine, respectively; and by 23% and 93% after exposure to 0.01 and 10 μM Glyphosate, respectively. There were no significant differences in growth. Changes in gene expression occurred in all genes, highlighting the expression of sod-1, sod-4, and gpx-4 that increased more than two-fold after exposure to 600 μM ABF and 10 μM GBF. The effects observed for the mixture of these formulations were additive for lethality, locomotion and fertility. In short, GBF, ABF, and their mixture induced several toxic responses related to oxidative stress on C. elegans. Copyright © 2018 Elsevier Inc. All rights reserved.

Aquatic toxicity of photo-degraded insensitive munition 101 (IMX-101) constituents.

PubMed

Kennedy, Alan J; Poda, Aimee R; Melby, Nicolas L; Moores, Lee C; Jordan, Shinita M; Gust, Kurt A; Bednar, Anthony J

2017-08-01

Insensitive munitions are desirable alternatives to historically used formulations, such as 2,4,6-trinitrotoluene (TNT), because of their so-called insensitivity to unintended detonation. The insensitive munition IMX-101 is a mixture of 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ). Environmental releases of munitions may be from production wastewaters or training; these munitions may be exposed to ultraviolet (UV) light. Therefore, it is useful to understand the relative toxicity of IMX-101 and its constituents both before and after photodegradation. The intent of the present study was to generate relative hazard information by exposing the standard ecotoxicological model Ceriodaphnia dubia to each insensitive munition constituent individually and to IMX-101 before and after the exposure solution was irradiated in a UV photoreactor. Without photodegradation, DNAN was more toxic (median lethal concentration [LC50] = 43 mg/L) than the other 2 constituents and it contributed predominantly to the toxicity of IMX-101 (LC50 = 206 mg/L) based on toxic units. Toxicity was observed only at high levels of NQ (LC50 = 1174 mg/L) and pH-adjusted NTO (LC50 = 799 mg/L). The toxicity of IMX-101 is lower than literature-reported TNT toxicity. Photodegradation efficiency was greater at lower insensitive munition concentrations. The observed degradation was greatest for NQ (42-99%), which in turn corresponded to the greatest relative increase in toxicity (100-1000-fold). Modest percent of degradation (4-18%) and increases in phototoxicity (2-100-fold) were observed for NTO and DNAN. Photodegraded NQ products were the predominant source of toxicity of photodegraded IMX-101. Future work involves research to enable analytical and computational confirmation of the specific degradation compounds inducing the observed photoenhanced toxicity. Environ Toxicol Chem 2017;36:2050-2057. Published 2017 Wiley Periodicals Inc. on

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish).

PubMed

Watanabe, Haruna; Tamura, Ikumi; Abe, Ryoko; Takanobu, Hitomi; Nakamura, Ataru; Suzuki, Toshinari; Hirose, Akihiko; Nishimura, Tetsuji; Tatarazako, Norihisa

2016-04-01

Principles of concentration addition and independent action have been used as effective tools to predict mixture toxicity based on individual component toxicity. The authors investigated the toxicity of a pharmaceutical mixture composed of the top 10 detected active pharmaceutical ingredients (APIs) in the Tama River (Tokyo, Japan) in a relevant concentration ratio. Both individual and mixture toxicities of the 10 APIs were evaluated by 3 short-term chronic toxicity tests using the alga Pseudokirchneriella subcapitata, the daphnid Ceriodaphnia dubia, and the zebrafish Danio rerio. With the exception of clarithromycin toxicity to alga, the no-observed-effect concentration of individual APIs for each test species was dramatically higher than the highest concentration of APIs found in the environment. The mixture of 10 APIs resulted in toxicity to alga, daphnid, and fish at 6.25 times, 100 times, and 15,000 times higher concentrations, respectively, than the environmental concentrations of individual APIs. Predictions by concentration addition and independent action were nearly identical for alga, as clarithromycin was the predominant toxicant in the mixture. Both predictions described the observed mixture toxicity to alga fairly well, whereas they slightly underestimated the observed mixture toxicity in the daphnid test. In the fish embryo test, the observed toxicity fell between the predicted toxicity by concentration addition and independent action. These results suggested that the toxicity of environmentally relevant pharmaceutical mixtures could be predicted by individual toxicity using either concentration addition or independent action. © 2015 SETAC.

[Two cases of toxic hepatitis caused by arrowroot juice].

PubMed

Kim, Seung Young; Yim, Hyung Joon; Ahn, Jae Hong; Kim, Jeong Han; Kim, Jin Nam; Yoon, Ik; Kim, Dong Il; Lee, Hong Sik; Lee, Sang Woo; Choi, Jai Hyun

2009-12-01

Herbal remedies and health foods are widely used, and their side effects have been reported. We describe two cases of symptomatic toxic hepatitis that developed in middle-aged women after ingesting arrowroot juice. The clinical manifestations were nausea, vomiting, and jaundice. The diagnosis of toxic hepatitis was made using the Roussel Uclaf Causality Assessment Method score on the basis of the patient's history and laboratory data. After supportive care, the patients showed rapid improvements of clinical symptoms, laboratory findings, and liver stiffness. Clinicians should be aware that the consumption of arrowroot juice can cause toxic hepatitis.

Physics-based scoring of protein-ligand interactions: explicit polarizability, quantum mechanics and free energies.

PubMed

Bryce, Richard A

2011-04-01

The ability to accurately predict the interaction of a ligand with its receptor is a key limitation in computer-aided drug design approaches such as virtual screening and de novo design. In this article, we examine current strategies for a physics-based approach to scoring of protein-ligand affinity, as well as outlining recent developments in force fields and quantum chemical techniques. We also consider advances in the development and application of simulation-based free energy methods to study protein-ligand interactions. Fuelled by recent advances in computational algorithms and hardware, there is the opportunity for increased integration of physics-based scoring approaches at earlier stages in computationally guided drug discovery. Specifically, we envisage increased use of implicit solvent models and simulation-based scoring methods as tools for computing the affinities of large virtual ligand libraries. Approaches based on end point simulations and reference potentials allow the application of more advanced potential energy functions to prediction of protein-ligand binding affinities. Comprehensive evaluation of polarizable force fields and quantum mechanical (QM)/molecular mechanical and QM methods in scoring of protein-ligand interactions is required, particularly in their ability to address challenging targets such as metalloproteins and other proteins that make highly polar interactions. Finally, we anticipate increasingly quantitative free energy perturbation and thermodynamic integration methods that are practical for optimization of hits obtained from screened ligand libraries.

Comparison of two screening bioassays, based on the frog sciatic nerve and yeast cells, for the assessment of herbicide toxicity.

PubMed

Papaefthimiou, Chrisovalantis; Cabral, Maria de Guadalupe; Mixailidou, Christina; Viegas, Cristina A; Sá-Correia, Isabel; Theophilidis, George

2004-05-01

Two different test systems, one based on the isolated sciatic nerve of an amphibian and the other on a microbial eukaryote, were used for the assessment of herbicide toxicity. More specifically, we determined the deleterious effects of increasing concentrations of herbicides of different chemical classes (phenoxyacetic acids, triazines, and acetamides), and of 2,4-dichlorophenol (2,4-DCP), a degradation product of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), on electrophysiological parameters and the vitality of the axons of the isolated sciatic nerve of the frog (Rana ridibunda) and on the growth curve of the yeast Saccharomyces cerevisiae based on microtiter plate susceptibility assays. The no-observed-effect-concentration (NOEC), defined as the maximum concentration of the tested compound that has no effect on these biological parameters, was estimated. In spite of the different methodological approaches and biological systems compared, the NOEC values were identical and correlated with the lipophilicity of the tested compounds. The relative toxicity established here, 2,4-DCP > alachlor, metolachlor > metribuzin > 2,4-D, 2-methyl-4-chlorophenoxyacetic acid (MCPA), correlates with the toxicity indexes reported in the literature for freshwater organisms. Based on these results, we suggest that the relatively simple, rapid, and low-cost test systems examined here may be of interest as alternative or complementary tests for toxicological assessment of herbicides.

Multi-class Mode of Action Classification of Toxic Compounds Using Logic Based Kernel Methods.

PubMed

Lodhi, Huma; Muggleton, Stephen; Sternberg, Mike J E

2010-09-17

Toxicity prediction is essential for drug design and development of effective therapeutics. In this paper we present an in silico strategy, to identify the mode of action of toxic compounds, that is based on the use of a novel logic based kernel method. The technique uses support vector machines in conjunction with the kernels constructed from first order rules induced by an Inductive Logic Programming system. It constructs multi-class models by using a divide and conquer reduction strategy that splits multi-classes into binary groups and solves each individual problem recursively hence generating an underlying decision list structure. In order to evaluate the effectiveness of the approach for chemoinformatics problems like predictive toxicology, we apply it to toxicity classification in aquatic systems. The method is used to identify and classify 442 compounds with respect to the mode of action. The experimental results show that the technique successfully classifies toxic compounds and can be useful in assessing environmental risks. Experimental comparison of the performance of the proposed multi-class scheme with the standard multi-class Inductive Logic Programming algorithm and multi-class Support Vector Machine yields statistically significant results and demonstrates the potential power and benefits of the approach in identifying compounds of various toxic mechanisms. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acute Human Lethal Toxicity of Agricultural Pesticides: A Prospective Cohort Study

PubMed Central

Senarathna, Lalith; Mohamed, Fahim; Gawarammana, Indika; Bowe, Steven J.; Manuweera, Gamini; Buckley, Nicholas A.

2010-01-01

Background Agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000–370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy. Methods and Findings We examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides—from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications. Conclusion The human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner. Please see later in the

Toxicity of urban highway runoff with respect to storm duration.

PubMed

Kayhanian, M; Stransky, C; Bay, S; Lau, S-L; Stenstrom, M K

2008-01-25

The toxicity of stormwater runoff during various time-based stages was measured in both grab and composite samples collected from three highly urbanized highway sites in Los Angeles, California between 2002 and 2005. Stormwater runoff samples were tested for toxicity using three freshwater species (the water flea Ceriodaphnia dubia, the fathead minnow Pimephales promelas, and the green algae Pseudokirchneriella subcapitatum) and two marine species (the purple sea urchin Strongylocentrotus purpuratus, and the luminescent bacteria Photobacterium phosphoreum using Microtox. Toxicity results varied substantially throughout the storm events for both freshwater and marine species toxicity tests. In general, however, the first few samples were found to be more toxic compared with those collected during later stages of each storm event. In most cases, more than 40% of the toxicity was associated with the first 20% of discharged runoff volume. Furthermore, on average, 90% of the toxicity was observed during the first 30% of storm duration. Toxicity identification evaluation results found copper and zinc to be the primary cause of toxicity in about 90% of the samples evaluated with these procedures. Surfactants were also found to be the cause of toxicity in less than 10% of the samples.

In silico quantitative structure-toxicity relationship study of aromatic nitro compounds.

PubMed

Pasha, Farhan Ahmad; Neaz, Mohammad Morshed; Cho, Seung Joo; Ansari, Mohiuddin; Mishra, Sunil Kumar; Tiwari, Sharvan

2009-05-01

Small molecules often have toxicities that are a function of molecular structural features. Minor variations in structural features can make large difference in such toxicity. Consequently, in silico techniques may be used to correlate such molecular toxicities with their structural features. Relative to nine different sets of aromatic nitro compounds having known observed toxicities against different targets, we developed ligand-based 2D quantitative structure-toxicity relationship models using 20 selected topological descriptors. The topological descriptors have several advantages such as conformational independency, facile and less time-consuming computation to yield good results. Multiple linear regression analysis was used to correlate variations of toxicity with molecular properties. The information index on molecular size, lopping centric index and Kier flexibility index were identified as fundamental descriptors for different kinds of toxicity, and further showed that molecular size, branching and molecular flexibility might be particularly important factors in quantitative structure-toxicity relationship analysis. This study revealed that topological descriptor-guided quantitative structure-toxicity relationship provided a very useful, cost and time-efficient, in silico tool for describing small-molecule toxicities.

Assessment of environmental risks from toxic and nontoxic stressors; a proposed concept for a risk-based management tool for offshore drilling discharges.

PubMed

Smit, Mathijs G D; Jak, Robbert G; Rye, Henrik; Frost, Tone Karin; Singsaas, Ivar; Karman, Chris C

2008-04-01

In order to improve the ecological status of aquatic systems, both toxic (e.g., chemical) and nontoxic stressors (e.g., suspended particles) should be evaluated. This paper describes an approach to environmental risk assessment of drilling discharges to the sea. These discharges might lead to concentrations of toxic compounds and suspended clay particles in the water compartment and concentrations of toxic compounds, burial of biota, change in sediment structure, and oxygen depletion in marine sediments. The main challenges were to apply existing protocols for environmental risk assessment to nontoxic stressors and to combine risks arising from exposure to these stressors with risk from chemical exposure. The defined approach is based on species sensitivity distributions (SSDs). In addition, precautionary principles from the EU-Technical Guidance Document were incorporated to assure that the method is acceptable in a regulatory context. For all stressors a protocol was defined to construct an SSD for no observed effect concentrations (or levels; NOEC(L)-SSD) to allow for the calculation of the potentially affected fraction of species from predicted exposures. Depending on the availability of data, a NOEC-SSD for toxicants can either be directly based on available NOECs or constructed from the predicted no effect concentration and the variation in sensitivity among species. For nontoxic stressors a NOEL-SSD can be extrapolated from an SSD based on effect or field data. Potentially affected fractions of species at predicted exposures are combined into an overall risk estimate. The developed approach facilitates environmental management of drilling discharges and can be applied to define risk-mitigating measures for both toxic and nontoxic stress.

A mixture toxicity approach to predict the toxicity of Ag decorated ZnO nanomaterials.

PubMed

Azevedo, S L; Holz, T; Rodrigues, J; Monteiro, T; Costa, F M; Soares, A M V M; Loureiro, S

2017-02-01

Nanotechnology is a rising field and nanomaterials can now be found in a vast variety of products with different chemical compositions, sizes and shapes. New nanostructures combining different nanomaterials are being developed due to their enhancing characteristics when compared to nanomaterials alone. In the present study, the toxicity of a nanostructure composed by a ZnO nanomaterial with Ag nanomaterials on its surface (designated as ZnO/Ag nanostructure) was assessed using the model-organism Daphnia magna and its toxicity predicted based on the toxicity of the single components (Zn and Ag). For that ZnO and Ag nanomaterials as single components, along with its mixture prepared in the laboratory, were compared in terms of toxicity to ZnO/Ag nanostructures. Toxicity was assessed by immobilization and reproduction tests. A mixture toxicity approach was carried out using as starting point the conceptual model of Concentration Addition. The laboratory mixture of both nanomaterials showed that toxicity was dependent on the doses of ZnO and Ag used (immobilization) or presented a synergistic pattern (reproduction). The ZnO/Ag nanostructure toxicity prediction, based on the percentage of individual components, showed an increase in toxicity when compared to the expected (immobilization) and dependent on the concentration used (reproduction). This study demonstrates that the toxicity of the prepared mixture of ZnO and Ag and of the ZnO/Ag nanostructure cannot be predicted based on the toxicity of their components, highlighting the importance of taking into account the interaction between nanomaterials when assessing hazard and risk. Copyright © 2016 Elsevier B.V. All rights reserved.

Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells.

PubMed

Murmann, Andrea E; Gao, Quan Q; Putzbach, William E; Patel, Monal; Bartom, Elizabeth T; Law, Calvin Y; Bridgeman, Bryan; Chen, Siquan; McMahon, Kaylin M; Thaxton, C Shad; Peter, Marcus E

2018-03-01

Trinucleotide repeat (TNR) expansions in the genome cause a number of degenerative diseases. A prominent TNR expansion involves the triplet CAG in the huntingtin (HTT) gene responsible for Huntington's disease (HD). Pathology is caused by protein and RNA generated from the TNR regions including small siRNA-sized repeat fragments. An inverse correlation between the length of the repeats in HTT and cancer incidence has been reported for HD patients. We now show that siRNAs based on the CAG TNR are toxic to cancer cells by targeting genes that contain long reverse complementary TNRs in their open reading frames. Of the 60 siRNAs based on the different TNRs, the six members in the CAG/CUG family of related TNRs are the most toxic to both human and mouse cancer cells. siCAG/CUG TNR-based siRNAs induce cell death in vitro in all tested cancer cell lines and slow down tumor growth in a preclinical mouse model of ovarian cancer with no signs of toxicity to the mice. We propose to explore TNR-based siRNAs as a novel form of anticancer reagents. © 2018 The Authors.

STRESS PATHWAY-BASED REPORTER ASSAYS TO ASSESS TOXICITY OF ENVIRONMENTAL CHEMICALS.

EPA Science Inventory

There is an increasing need for assays for the rapid and efficient assessment of toxicities of large numbers of environmental chemicals. To meet this need, we are developing cell-based reporter assays that measure the activation of key molecular stress pathways. We are using pro...

A Simple Symptom Score for Acute HIV Infection in a San Diego Community Based Screening Program.

PubMed

Lin, Timothy C; Gianella, Sara; Tenenbaum, Tara; Little, Susan J; Hoenigl, Martin

2017-12-25

Treatment of acute HIV infection (AHI) decreases transmission and preserves immune function, but AHI diagnosis remains resource-intensive. Risk-based scores predictive for AHI have been described for high-risk groups, however symptom-based scores could be more generalizable across populations. Adults who tested either positive for AHI (antibody-negative, HIV nucleic acid test [NAT]-positive) or HIV NAT-negative with the community-based Early Test HIV screening program in San Diego were retrospectively randomized 2:1 into a derivation and validation set. In the former, symptoms significant for AHI in a multivariate logistic regression model were assigned a score value (the odds ratio rounded to the nearest integer). The score was assessed in the validation set using receiver operating characteristics and areas under the curve (AUC). An optimal cut-off score was found using Youden's index. Of 998 participants (including 737 men who have sex with men (MSM), 149 non-MSM men, 109 ciswomen and 3 trans women), 113 had AHI (including 109 MSM). Compared to HIV-negative cases, AHI cases reported more symptoms (median 4 vs 0, p<0.01). Fever, myalgia and weight loss were significantly associated with AHI in the multivariate model and corresponded to 11, 8 and 4 score points, respectively. The summed score yielded AUC of 0.85 (95%CI 0.77-0.93). A score of ≥11 was 72% sensitive, 96% specific with diagnostic odds ratio of 70.27 (95%CI 28.14-175.93). A 3-symptom score accurately predicted AHI in a community based screening program and may inform allocation of resources in settings that do not routinely screen for AHI. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Toxic metals in Venics lagoon sediments: Model, observation, an possible removal

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

Basu, A.; Molinaroli, E.

1994-11-01

We have modeled the distribution of nine toxic metals in the surface sediments from 163 stations in the Venice lagoon using published data. Three entrances from the Adriatic Sea control the circulation in the lagoon and divide it into three basins. We assume, for purposes of modeling, that Porto Marghera at the head of the Industrial Zone area is the single source of toxic metals in the Venice lagoon. In a standing body of lagoon water, concentration of pollutants at distance x from the source (C{sub 0}) may be given by C=C{sub 0}e{sup -kx} where k is the rate constantmore » of dispersal. We calculated k empirically using concentrations at the source, and those farthest from it, that is the end points of the lagoon. Average k values (ppm/km) in the lagoon are: Zn 0.165, Cd 0.116, Hg 0.110, Cu 0.105, Co 0.072, Pb 0.058, Ni 0.008, Cr (0.011) and Fe (0.018 percent/km), and they have complex distributions. Given the k values, concentration at source (C{sub 0}), and the distance x of any point in the lagoon from the source, we have calculated the model concentrations of the nine metals at each sampling station. Tides, currents, floor morphology, additional sources, and continued dumping perturb model distributions causing anomalies (observed minus model concentrations). Positive anomalies are found near the source, where continued dumping perturbs initial boundary conditions, and in areas of sluggish circulation. Negative anomalies are found in areas with strong currents that may flush sediments out of the lagoon. We have thus identified areas in the lagoon where higher rate of sediment removal and exchange may lesson pollution. 41 refs., 4 figs., 3 tabs.« less

The TAIGA timing array HiSCORE - first results

NASA Astrophysics Data System (ADS)

Tluczykont, M.; Budnev, N.; Astapov, I.; Barbashina, N.; Bogdanov, A.; Boreyko, V.; Brückner, M.; Chiavassa, A.; Chvalaev, O.; Gress, O.; Gress, T.; Grishin, O.; Dyachok, A.; Epimakhov, S.; Fedorov, O.; Gafarov, A.; Gorbunov, N.; Grebenyuk, V.; Grinuk, A.; Horns, D.; Kalinin, A.; Karpov, N.; Kalmykov, N.; Kazarina, Y.; Kiryuhin, S.; Kokoulin, R.; Kompaniets, K.; Konstantinov, A.; Korosteleva, E.; Kozhin, V.; Kravchenko, E.; Kunnas, M.; Kuzmichev, L.; Lemeshev, Yu.; Lubsandorzhiev, B.; Lubsandorzhiev, N.; Mirgazov, R.; Mirzoyan, R.; Monkhoev, R.; Nachtigall, R.; Osipova, E.; Pakhorukov, A.; Panasyuk, M.; Pankov, L.; Petrukhin, A.; Poleschuk, V.; Popova, E.; Porelli, A.; Postnikov, E.; Prosin, V.; Ptuskin, V.; Rubtsov, G.; Pushnin, A.; Samoliga, V.; Satunin, P.; Semeney, Yu.; Silaev, A.; Silaev, A.; Skurikhin, A.; Slunecka, M.; Sokolov, A.; Spiering, C.; Sveshnikova, L.; Tabolenko, V.; Tarashansky, B.; Tkachenko, A.; Tkachev, L.; Voronin, D.; Wischnewski, R.; Zagorodnikov, A.; Zurbanov, V.; Zhurov, D.; Yashin, I.

2017-03-01

Observations of gamma rays up to several 100 TeV are particularly important to spectrally resolve the cutoff regime of the long-sought Pevatrons, the cosmic-ray PeV accelerators. One component of the TAIGA hybrid detector is the TAIGA-HiSCORE timing array, which currently consists of 28 wide angle (0.6 sr) air Cherenkov timing stations distributed on an area of 0.25 km2. The HiSCORE concept is based on (non-imaging) air shower front sampling with Cherenkov light. First results are presented.

A novel approach for rapidly and cost-effectively assessing toxicity of toxic metals in acidic water using an acidophilic iron-oxidizing biosensor.

PubMed

Yang, Shih-Hung; Cheng, Kuo-Chih; Liao, Vivian Hsiu-Chuan

2017-11-01

Contamination by heavy metals and metalloids is a serious environmental and health concern. Acidic wastewaters are often associated with toxic metals which may enter and spread into agricultural soils. Several biological assays have been developed to detect toxic metals; however, most of them can only detect toxic metals in a neutral pH, not in an acidic environment. In this study, an acidophilic iron-oxidizing bacterium (IOB) Strain Y10 was isolated, characterized, and used to detect toxic metals toxicity in acidic water at pH 2.5. The colorimetric acidophilic IOB biosensor was based on the inhibition of the iron oxidizing ability of Strain Y10, an acidophilic iron-oxidizing bacterium, by metals toxicity. Our results showed that Strain Y10 is acidophilic iron-oxidizing bacterium. Thiobacillus caldus medium (TCM) (pH 2.5) supplied with both S 4 O 6 2- and glucose was the optimum growth medium for Strain Y10. The optimum temperature and pH for the growth of Strain Y10 was 45 °C and pH 2.5, respectively. Our study demonstrates that the color-based acidophilic IOB biosensor can be semi-quantitatively observed by eye or quantitatively measured by spectrometer to detect toxicity from multiple toxic metals at pH 2.5 within 45 min. Our study shows that monitoring toxic metals in acidic water is possible by using the acidophilic IOB biosensor. Our study thus provides a novel approach for rapid and cost-effective detection of toxic metals in acidic conditions that can otherwise compromise current methods of chemical analysis. This method also allows for increased efficiency when screening large numbers of environmental samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Veterans Affairs Cardiac Risk Score: Recalibrating the Atherosclerotic Cardiovascular Disease Score for Applied Use.

PubMed

Sussman, Jeremy B; Wiitala, Wyndy L; Zawistowski, Matthew; Hofer, Timothy P; Bentley, Douglas; Hayward, Rodney A

2017-09-01

Accurately estimating cardiovascular risk is fundamental to good decision-making in cardiovascular disease (CVD) prevention, but risk scores developed in one population often perform poorly in dissimilar populations. We sought to examine whether a large integrated health system can use their electronic health data to better predict individual patients' risk of developing CVD. We created a cohort using all patients ages 45-80 who used Department of Veterans Affairs (VA) ambulatory care services in 2006 with no history of CVD, heart failure, or loop diuretics. Our outcome variable was new-onset CVD in 2007-2011. We then developed a series of recalibrated scores, including a fully refit "VA Risk Score-CVD (VARS-CVD)." We tested the different scores using standard measures of prediction quality. For the 1,512,092 patients in the study, the Atherosclerotic cardiovascular disease risk score had similar discrimination as the VARS-CVD (c-statistic of 0.66 in men and 0.73 in women), but the Atherosclerotic cardiovascular disease model had poor calibration, predicting 63% more events than observed. Calibration was excellent in the fully recalibrated VARS-CVD tool, but simpler techniques tested proved less reliable. We found that local electronic health record data can be used to estimate CVD better than an established risk score based on research populations. Recalibration improved estimates dramatically, and the type of recalibration was important. Such tools can also easily be integrated into health system's electronic health record and can be more readily updated.

Higher Blood Harmane (1-Methyl-9h-Pyrido[3,4-B]Indole) Concentrations Correlate With Lower Olfactory Scores In Essential Tremor

PubMed Central

Louis, Elan D.; Rios, Eileen; Pellegrino, Kathryn M.; Jiang, Wendy; Factor-Litvak, Pam; Zheng, Wei

2008-01-01

Background Harmane (1-methyl-9H-pyrido[3,4-b]indole), a neurotoxin, may be an environmental risk factor for essential tremor (ET). Harmane and related chemicals are toxic to the cerebellum. Whether it is through this mechanism (cerebellar toxicity) that harmane leads to ET is unknown. Impaired olfaction may be a feature of cerebellar disease. Objective To determine whether blood harmane concentrations correlate with olfactory test scores in patients with ET. Methods Blood harmane concentrations were quantified using high performance liquid chromatography. Odor identification testing was performed with the University of Pennsylvania Smell Identification Test (UPSIT). Results In 83 ET cases, higher log blood harmane concentration was correlated with lower UPSIT score (rho = −0.46, p < 0.001). 25/40 (62.5%) cases with high log blood harmane concentration (based on a median split) had low UPSIT scores (based on a median split) vs. 12/43 (27.9%) ET cases with low log blood harmane concentration (adjusted OR 4.04, 95% CI 1.42 – 11.50, p = 0.009). When compared with the low log blood harmane tertile, the odds of olfactory dysfunction were 2.64 times higher in cases in the middle tertile and 10.95 times higher in cases in the high tertile. In 69 control subjects, higher log blood harmane concentration was not correlated with lower UPSIT score (rho = 0.12, p = 0.32). Conclusions Blood harmane concentrations were correlated with UPSIT scores in ET cases but not controls. These analyses set the stage for postmortem studies to further explore the role of harmane as a cerebellar toxin in ET. PMID:18417221

How toxic is coal ash? A laboratory toxicity case study

DOE PAGES

Sherrard, Rick M.; Carriker, Neil; Greeley, Jr., Mark Stephen

2014-12-08

Under a consent agreement among the Environmental Protection Agency (EPA) and proponents both for and against stricter regulation, EPA is to issue a new coal ash disposal rule by the end of 2014. Laboratory toxicity investigations often yield conservative estimates of toxicity because many standard test species are more sensitive than resident species, thus could provide information useful to the rule-making. However, few laboratory studies of coal ash toxicity are available; most studies reported in the literature are based solely on field investigations. In this paper, we describe a broad range of toxicity studies conducted for the Tennessee Valley Authoritymore » (TVA) Kingston ash spill, results of which help provide additional perspective on the toxicity of coal ash.« less

New scoring system for intra-abdominal injury diagnosis after blunt trauma.

PubMed

Shojaee, Majid; Faridaalaee, Gholamreza; Yousefifard, Mahmoud; Yaseri, Mehdi; Arhami Dolatabadi, Ali; Sabzghabaei, Anita; Malekirastekenari, Ali

2014-01-01

An accurate scoring system for intra-abdominal injury (IAI) based on clinical manifestation and examination may decrease unnecessary CT scans, save time, and reduce healthcare cost. This study is designed to provide a new scoring system for a better diagnosis of IAI after blunt trauma. This prospective observational study was performed from April 2011 to October 2012 on patients aged above 18 years and suspected with blunt abdominal trauma (BAT) admitted to the emergency department (ED) of Imam Hussein Hospital and Shohadaye Hafte Tir Hospital. All patients were assessed and treated based on Advanced Trauma Life Support and ED protocol. Diagnosis was done according to CT scan findings, which was considered as the gold standard. Data were gathered based on patient's history, physical exam, ultrasound and CT scan findings by a general practitioner who was not blind to this study. Chi-square test and logistic regression were done. Factors with significant relationship with CT scan were imported in multivariate regression models, where a coefficient (β) was given based on the contribution of each of them. Scoring system was developed based on the obtained total β of each factor. Altogether 261 patients (80.1% male) were enrolled (48 cases of IAI). A 24-point blunt abdominal trauma scoring system (BATSS) was developed. Patients were divided into three groups including low (score<8), moderate (8≤score<12) and high risk (score≥12). In high risk group immediate laparotomy should be done, moderate group needs further assessments, and low risk group should be kept under observation. Low risk patients did not show positive CT-scans (specificity 100%). Conversely, all high risk patients had positive CT-scan findings (sensitivity 100%). The receiver operating characteristic curve indicated a close relationship between the results of CT scan and BATSS (sensitivity=99.3%). The present scoring system furnishes a high precision and reproducible diagnostic tool for BAT

Establishing a Th17 based mouse model for preclinical assessment of the toxicity of candidate microbicides.

PubMed

Li, Liang-Zhu; Yang, Yu; Yuan, Song-Hua; Wan, Yan-Min; Qiu, Chao; Feng, Yan-Ling; Xu, Jian-Qing; Zhang, Xiao-Yan

2010-12-01

To effectively block the invasion of human immunodeficiency virus (HIV)-1 on mucosal surface, vaginal anti-HIV-1 microbicides should avoid inflammatory responses and disruption of mucosa integrity because these will facilitate transepithelial viral penetration and replication. However, existing models fail to predict and evaluate vaginal mucosal toxicity induced by microbicides, and most importantly, they are unable to identify subtle or subclinical inflammatory reactions. This study was designed to develop a cost-effective in vivo model to evaluate microbicide safety in a preclinical study which can recapitulate the mucosal topical reaction. A murine model was employed with nonoxynol-9 (N-9) as the topical stimulant within the vagina. Different concentrations of N-9 (1%, 3%, and 4%) were topically applied to the vagina for five consecutive days. A panel of inflammatory cytokines including interleukine-2 (IL-2), IL-4, IL-6, IL-17A, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and immuno-regulatory IL-10 were assayed in vaginal lavage. Cytokines were quantified by using cytometric bead array (CBA) and reverse transcript (RT) real-time PCR. Histopathological evaluation of vaginal tissues was conducted on hematoxylin-eosin stained slides and scored with a semi-quantitative system according to the severity of epithelial disruption, leucocyte infiltration, edema, and vascular injection. The association between the cytokines and histopathological scores was assessed by linear regression analysis. All three concentrations of N-9 induced inflammatory cytokine production. The 4% N-9 application resulted in a consistent production of cytokines in a time-dependent manner. The cytokines reached peak expression on day three with the exception of IL-4 which reached its peak on day one. Histopathological examination of 4% N-9 treated cervicovaginal tissues on day three showed intensive damage in four mice (sores: 10 - 13) and moderate damage in one mouse (score: 8

Predicting preference-based SF-6D index scores from the SF-8 health survey.

PubMed

Wang, P; Fu, A Z; Wee, H L; Lee, J; Tai, E S; Thumboo, J; Luo, N

2013-09-01

To develop and test functions for predicting the preference-based SF-6D index scores from the SF-8 health survey. This study was a secondary analysis of data collected in a population health survey in which respondents (n = 7,529) completed both the SF-36 and the SF-8 questionnaires. We examined seven ordinary least-square estimators for their performance in predicting SF-6D scores from the SF-8 at both the individual and the group levels. In general, all functions performed similarly well in predicting SF-6D scores, and the predictions at the group level were better than predictions at the individual level. At the individual level, 42.5-51.5% of prediction errors were smaller than the minimally important difference (MID) of the SF-6D scores, depending on the function specifications, while almost all prediction errors of the tested functions were smaller than the MID of SF-6D at the group level. At both individual and group levels, the tested functions predicted lower than actual scores at the higher end of the SF-6D scale. Our study developed functions to generate preference-based SF-6D index scores from the SF-8 health survey, the first of its kind. Further research is needed to evaluate the performance and validity of the prediction functions.

Toxicity Testing in the 21st Century: Defining New Risk Assessment Approaches Based on Perturbation of Intracellular Toxicity Pathways

PubMed Central

Bhattacharya, Sudin; Zhang, Qiang; Carmichael, Paul L.; Boekelheide, Kim; Andersen, Melvin E.

2011-01-01

The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC) report Toxicity Testing in the 21st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a) “toxicity pathways” (the innate cellular pathways that may be perturbed by chemicals) and (b) the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU). EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair. PMID:21701582

Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents

PubMed Central

Rocha, Luis B.; Schaberle, Fábio; Dąbrowski, Janusz M.; Simões, Sérgio; Arnaut, Luis G.

2015-01-01

We assessed the tolerability and safety in rodents of a single intravenous (i.v.) dose of redaporfin, a novel photosensitizer for Photodynamic Therapy (PDT) of cancer. Two approaches were used to evaluate acute toxicity: (i) a dose escalation study in BALB/c mice to evaluate the maximum tolerated dose of redaporfin; and (ii) a safety toxicology study in Wistar rats, of a single dose of redaporfin, with or without illumination, to evaluate possible signs of systemic toxicity. Redaporfin formulation was well tolerated by mice, with no signs of adverse reactions up to 75 mg/kg. In rats, there were no relevant changes, except for a significant, but transient, increase in the blood serum markers for hepatic function and muscle integrity, and also on neutrophil counts, observed after the application of light. The overall results showed that redaporfin-PDT is very well tolerated. No abnormalities were observed, including reactions at the injection site or skin phototoxicity, although the animals were maintained in normal indoor lighting. Redaporfin also showed a high efficacy in the treatment of male BALB/c mice with subcutaneously implanted colon (CT26) tumours. Vascular-PDT with 1.5 mg/kg redaporfin and a light dose of 74 J/cm2 led to the complete tumour regression in 83% of the mice. PMID:26670231

Cardiovascular Toxicity of Multi-Tyrosine Kinase Inhibitors in Advanced Solid Tumors: A Population-Based Observational Study

PubMed Central

Srikanthan, Amirrtha; Ethier, Josee-Lyne; Ocana, Alberto; Seruga, Bostjan; Krzyzanowska, Monika K.; Amir, Eitan

2015-01-01

Background Treatment with small molecule tyrosine kinase inhibitors (TKIs) has improved survival in many cancers, yet has been associated with an increased risk of adverse events. Warnings of cardiovascular events are common in drug labels of many TKIs. Despite these warnings, cardiovascular toxicity of patients treated with TKIs remains unclear. Here, we evaluate the cardiovascular outcomes of advanced cancer patients treated with small molecule tyrosine kinase inhibitors. Methods A population based cohort study was undertaken involving adults aged >18 years in Ontario, Canada, diagnosed with any advanced malignancy between 2006 and 2012. Data were extracted from linked administrative governmental databases. Adults with advanced cancer receiving TKIs were identified and followed throughout the time period. The main outcomes of interest were rates of hospitalization for ischemic heart disease (acute myocardial infarction and angina) or cerebrovascular accidents and death. Results 1642 patients with a mean age of 62.5 years were studied; 1046 were treated with erlotinib, 166 with sorafenib and 430 with sunitinib. Over the 380 day median follow-up period (range 6-1970 days), 1.1% of all patients had ischemic heart events, 0.7% had cerebrovascular accidents and 72.1% died. Rates of cardiovascular events were similar to age and gender-matched individuals without cancer. In a subgroup analysis of treatment patients with a prior history of ischemic heart disease, 3.3% had ischemic heart events while 1.2% had cerebrovascular accidents. Conclusions TKIs do not appear to increase the cause-specific hazard of ischemic heart disease and cerebrovascular accidents compared to age and gender-matched individuals without advanced cancer. PMID:25815472

Impact of Moodle-Based Online Curriculum on Thoracic Surgery In-Training Examination Scores.

PubMed

Antonoff, Mara B; Verrier, Edward D; Allen, Mark S; Aloia, Lauren; Baker, Craig; Fann, James I; Iannettoni, Mark D; Yang, Stephen C; Vaporciyan, Ara A

2016-10-01

The feasibility and efficacy of a web-based curriculum in supplementing thoracic surgical training was previously shown. However, the impact of curricular participation on validated knowledge tests remains unknown. We compared in-service training examination (ITE) results among trainees, stratified by curricular use. The national online curriculum was implemented in August 2013. We retrospectively reviewed trainees who participated in thoracic surgical training programs in both 2012 to 2013 and 2013 to 2014. Scores from the 2013 and 2014 ITEs were obtained, and curricular usage data were collected from site analytics. Trainees were separated into three groups according to 2013 ITE scores; within each group, changes in score for high- versus low-volume users were compared. 187 trainees took the ITE both years, with exposure to the online curriculum during only the second year. High-volume users' scores trended toward greater improvement than scores of low-volume users (+18.2% versus +13.0%, p = 0.199). When stratified by 2013 score, the lowest scoring quartile improved substantially, and the highest scoring quartile improved modestly, regardless of curricular use. However, for those individuals who achieved mid-range scores in 2013, there was a trend toward much greater improvement in score with heavier use of the curriculum (+17.0% versus +7.0%, p = 0.094). Among trainees who had access to the novel online curriculum during the second of 2 consecutive years, we evaluated the impact of curricular participation on ITE scores. The effect appears to be most pronounced in individuals with mid-range scores, in whom high curricular use led to the greatest improvement. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Equating Scores from Adaptive to Linear Tests

ERIC Educational Resources Information Center

van der Linden, Wim J.

2006-01-01

Two local methods for observed-score equating are applied to the problem of equating an adaptive test to a linear test. In an empirical study, the methods were evaluated against a method based on the test characteristic function (TCF) of the linear test and traditional equipercentile equating applied to the ability estimates on the adaptive test…

Centile-based early warning scores derived from statistical distributions of vital signs.

PubMed

Tarassenko, Lionel; Clifton, David A; Pinsky, Michael R; Hravnak, Marilyn T; Woods, John R; Watkinson, Peter J

2011-08-01

To develop an early warning score (EWS) system based on the statistical properties of the vital signs in at-risk hospitalised patients. A large dataset comprising 64,622 h of vital-sign data, acquired from 863 acutely ill in-hospital patients using bedside monitors, was used to investigate the statistical properties of the four main vital signs. Normalised histograms and cumulative distribution functions were plotted for each of the four variables. A centile-based alerting system was modelled using the aggregated database. The means and standard deviations of our population's vital signs are very similar to those published in previous studies. When compared with EWS systems based on a future outcome, the cut-off values in our system are most different for respiratory rate and systolic blood pressure. With four-hourly observations in a 12-h shift, about 1 in 8 at-risk patients would trigger our alerting system during the shift. A centile-based EWS system will identify patients with abnormal vital signs regardless of their eventual outcome and might therefore be more likely to generate an alert when presented with patients with redeemable morbidity or avoidable mortality. We are about to start a stepped-wedge clinical trial gradually introducing an electronic version of our EWS system on the trauma wards in a teaching hospital. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

System-based Identification of Toxicity Pathways Associated With Multi-Walled Carbon Nanotube-Induced Pathological Responses

PubMed Central

Snyder-Talkington, Brandi N.; Dymacek, Julian; Porter, Dale W.; Wolfarth, Michael G.; Mercer, Robert R.; Pacurari, Maricica; Denvir, James; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

2014-01-01

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 µg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and were used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. PMID:23845593

Building a developmental toxicity ontology.

PubMed

Baker, Nancy; Boobis, Alan; Burgoon, Lyle; Carney, Edward; Currie, Richard; Fritsche, Ellen; Knudsen, Thomas; Laffont, Madeleine; Piersma, Aldert H; Poole, Alan; Schneider, Steffen; Daston, George

2018-04-03

As more information is generated about modes of action for developmental toxicity and more data are generated using high-throughput and high-content technologies, it is becoming necessary to organize that information. This report discussed the need for a systematic representation of knowledge about developmental toxicity (i.e., an ontology) and proposes a method to build one based on knowledge of developmental biology and mode of action/ adverse outcome pathways in developmental toxicity. This report is the result of a consensus working group developing a plan to create an ontology for developmental toxicity that spans multiple levels of biological organization. This report provide a description of some of the challenges in building a developmental toxicity ontology and outlines a proposed methodology to meet those challenges. As the ontology is built on currently available web-based resources, a review of these resources is provided. Case studies on one of the most well-understood morphogens and developmental toxicants, retinoic acid, are presented as examples of how such an ontology might be developed. This report outlines an approach to construct a developmental toxicity ontology. Such an ontology will facilitate computer-based prediction of substances likely to induce human developmental toxicity. © 2018 Wiley Periodicals, Inc.

Cutoff value of Japanese Orthopaedic Association shoulder score in patients with rotator cuff repair: Based on the University of California at Los Angeles shoulder score.

PubMed

Imai, Takaki; Gotoh, Masafumi; Tokunaga, Tsuyoshi; Kawakami, Jyunichi; Mitsui, Yasuhiro; Fukuda, Keiji; Ogino, Misa; Okawa, Takahiro; Shiba, Naoto

2017-05-01

The Japanese Orthopaedic Association shoulder score cutoff values were calculated in patients with rotator cuff repair using the University of California at Los Angeles shoulder score. Overall, 175 patients with rotator cuff repair were subjects in this study. The University of California at Los Angeles and Japanese Orthopaedic Association shoulder scores were evaluated before surgery and at 3, 6, 9, and 12 months after surgery. The cutoff value of the Japanese Orthopaedic Association shoulder score was determined using the 4-stage criteria of the University of California at Los Angeles shoulder score and a University of California at Los Angeles shoulder score of 28 points, which is the boundary between an excellent/good group and a fair/poor group. Both the JOA shoulder and UCLA shoulder scores showed significant improvement at 6, 9, and 12 months from the preoperative scores (p < 0.0001). There was a strong correlation between the total values of the two scores (r = 0.85, p < 0.0001). The cutoff value of the Japanese Orthopaedic Association shoulder score based on the highest accuracy from receiver operating characteristic curve analysis was 83 points. A Japanese Orthopaedic Association shoulder score cutoff value of 83 was equivalent to a University of California at Los Angeles shoulder score cutoff value of 28 for distinguishing between excellent/good and fair/poor outcomes after rotator cuff repair. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Rough sets and Laplacian score based cost-sensitive feature selection.

PubMed

Yu, Shenglong; Zhao, Hong

2018-01-01

Cost-sensitive feature selection learning is an important preprocessing step in machine learning and data mining. Recently, most existing cost-sensitive feature selection algorithms are heuristic algorithms, which evaluate the importance of each feature individually and select features one by one. Obviously, these algorithms do not consider the relationship among features. In this paper, we propose a new algorithm for minimal cost feature selection called the rough sets and Laplacian score based cost-sensitive feature selection. The importance of each feature is evaluated by both rough sets and Laplacian score. Compared with heuristic algorithms, the proposed algorithm takes into consideration the relationship among features with locality preservation of Laplacian score. We select a feature subset with maximal feature importance and minimal cost when cost is undertaken in parallel, where the cost is given by three different distributions to simulate different applications. Different from existing cost-sensitive feature selection algorithms, our algorithm simultaneously selects out a predetermined number of "good" features. Extensive experimental results show that the approach is efficient and able to effectively obtain the minimum cost subset. In addition, the results of our method are more promising than the results of other cost-sensitive feature selection algorithms.

DISTRIBUTED STRUCTURE-SEARCHABLE TOXICITY ...

EPA Pesticide Factsheets

The ability to assess the potential genotoxicity, carcinogenicity, or other toxicity of pharmaceutical or industrial chemicals based on chemical structure information is a highly coveted and shared goal of varied academic, commercial, and government regulatory groups. These diverse interests often employ different approaches and have different criteria and use for toxicity assessments, but they share a need for unrestricted access to existing public toxicity data linked with chemical structure information. Currently, there exists no central repository of toxicity information, commercial or public, that adequately meets the data requirements for flexible analogue searching, SAR model development, or building of chemical relational databases (CRD). The Distributed Structure-Searchable Toxicity (DSSTox) Public Database Network is being proposed as a community-supported, web-based effort to address these shared needs of the SAR and toxicology communities. The DSSTox project has the following major elements: 1) to adopt and encourage the use of a common standard file format (SDF) for public toxicity databases that includes chemical structure, text and property information, and that can easily be imported into available CRD applications; 2) to implement a distributed source approach, managed by a DSSTox Central Website, that will enable decentralized, free public access to structure-toxicity data files, and that will effectively link knowledgeable toxicity data s

Evaluation of toxicity and biodegradability of choline chloride based deep eutectic solvents.

PubMed

Radošević, Kristina; Bubalo, Marina Cvjetko; Srček, Višnje Gaurina; Grgas, Dijana; Dragičević, Tibela Landeka; Redovniković, Ivana Radojčić

2015-02-01

Deep eutectic solvents (DESs) have been dramatically expanding in popularity as a new generation of environmentally friendly solvents with possible applications in various industrial fields, but their ecological footprint has not yet been thoroughly investigated. In the present study, three choline chloride-based DESs with glucose, glycerol and oxalic acid as hydrogen bond donors were evaluated for in vitro toxicity using fish and human cell line, phytotoxicity using wheat and biodegradability using wastewater microorganisms through closed bottle test. Obtained in vitro toxicity data on cell lines indicate that choline chloride: glucose and choline chloride:glycerol possess low cytotoxicity (EC50>10 mM for both cell lines) while choline chloride:oxalic acid possess moderate cytotoxicity (EC50 value 1.64 mM and 4.19 mM for fish and human cell line, respectively). Results on phytotoxicity imply that tested DESs are non-toxic with seed germination EC50 values higher than 5000 mg L(-1). All tested DESs were classified as'readily biodegradable' based on their high levels of mineralization (68-96%). These findings indicate that DESs have a green profile and a good prospect for a wider use in the field of green technologies. Copyright © 2014 Elsevier Inc. All rights reserved.

Aquatic Toxicity Information Retrieval Data Base (ACQUIRE). Data file

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

Not Available

The purpose of Acquire is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for ACQUIRE. Independently compiled data files that meet ACQUIRE parameter and quality assurance criteria are also included. Selected toxicity test results and related testing information for any individual chemical from laboratory and field aquatic toxicity effects are included for tests with freshwater and marine organisms. The total number of data records in ACQUIRE is now over 105,300.more » This includes data from 6000 references, for 5200 chemicals and 2400 test species. A major data file, Acute Toxicity of Organic Chemicals (ATOC), has been incorporated into ACQUIRE. The ATOC file contains laboratory acute test data on 525 organic chemicals using juvenile fathead minnows.« less

Metal oxide nanoparticles with low toxicity.

PubMed

Ng, Alan Man Ching; Guo, Mu Yao; Leung, Yu Hang; Chan, Charis M N; Wong, Stella W Y; Yung, Mana M N; Ma, Angel P Y; Djurišić, Aleksandra B; Leung, Frederick C C; Leung, Kenneth M Y; Chan, Wai Kin; Lee, Hung Kay

2015-10-01

A number of different nanomaterials produced and incorporated into various products are rising. However, their environmental hazards are frequently unknown. Here we consider three different metal oxide compounds (SnO2, In2O3, and Al2O3), which have not been extensively studied and are expected to have low toxicity. This study aimed to comprehensively characterize the physicochemical properties of these nanomaterials and investigate their toxicity on bacteria (Escherichia coli) under UV illumination and in the dark, as well as on a marine diatom (Skeletonema costatum) under ambient illumination/dark (16-8h) cycles. The material properties responsible for their low toxicity have been identified based on comprehensive experimental characterizations and comparison to a metal oxide exhibiting significant toxicity under illumination (anatase TiO2). The metal oxide materials investigated exhibited significant difference in surface properties and interaction with the living organisms. In order for a material to exhibit significant toxicity, it needs to be able to both form a stable suspension in the culture medium and to interact with the cell walls of the test organism. Our results indicated that the observed low toxicities of the three nanomaterials could be attributed to the limited interaction between the nanoparticles and cell walls of the test organisms. This could occur either due to the lack of significant attachment between nanoparticles and cell walls, or due to their tendency to aggregate in solution. Copyright © 2015 Elsevier B.V. All rights reserved.

Gold leaching by organic base polythionates: new non-toxic and secure technology.

PubMed

Smolyaninov, Vladislav; Shekhvatova, Galina; Vainshtein, Mikhail

2014-01-01

The article present a review on own experimental and some published data which are related with the gold leaching. It is well-known that the most common and usual process of the leaching with cyanide can be dangerous, needs a great water consumption, and additional costs for remediation of the poisoned and toxic sites. The experimental data described production of poythionates which are not toxic but perspective for the prosperous gold leaching. The paper dedicated to the safe gold leaching with thiosulfates and organic salts of polythionic acids (organic base polythionates). The method of production of these polythionates based on the Smolyaninov reaction is described in stages and in details for the first time. Possible application of the polythionates application in the gold leaching is discussed and its advantages are compared with the gold leaching by cyanation.

Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity.

PubMed

Mesnage, R; Bernay, B; Séralini, G-E

2013-11-16

Pesticides are always used in formulations as mixtures of an active principle with adjuvants. Glyphosate, the active ingredient of the major pesticide in the world, is an herbicide supposed to be specific on plant metabolism. Its adjuvants are generally considered as inert diluents. Since side effects for all these compounds have been claimed, we studied potential active principles for toxicity on human cells for 9 glyphosate-based formulations. For this we detailed their compositions and toxicities, and as controls we used a major adjuvant (the polyethoxylated tallowamine POE-15), glyphosate alone, and a total formulation without glyphosate. This was performed after 24h exposures on hepatic (HepG2), embryonic (HEK293) and placental (JEG3) cell lines. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. The compositions in adjuvants were analyzed by mass spectrometry. Here we demonstrate that all formulations are more toxic than glyphosate, and we separated experimentally three groups of formulations differentially toxic according to their concentrations in ethoxylated adjuvants. Among them, POE-15 clearly appears to be the most toxic principle against human cells, even if others are not excluded. It begins to be active with negative dose-dependent effects on cellular respiration and membrane integrity between 1 and 3ppm, at environmental/occupational doses. We demonstrate in addition that POE-15 induces necrosis when its first micellization process occurs, by contrast to glyphosate which is known to promote endocrine disrupting effects after entering cells. Altogether, these results challenge the establishment of guidance values such as the acceptable daily intake of glyphosate, when these are mostly based on a long term in vivo test of glyphosate alone. Since pesticides are always used with adjuvants that could change their toxicity, the necessity to assess their whole formulations as mixtures becomes obvious. This challenges

Observer Use of Standardized Observation Protocols in Consequential Observation Systems

ERIC Educational Resources Information Center

Bell, Courtney A.; Yi, Qi; Jones, Nathan D.; Lewis, Jennifer M.; McLeod, Monica; Liu, Shuangshuang

2014-01-01

Evidence from a handful of large-scale studies suggests that although observers can be trained to score reliably using observation protocols, there are concerns related to initial training and calibration activities designed to keep observers scoring accurately over time (e.g., Bell, et al, 2012; BMGF, 2012). Studies offer little insight into how…

A Critical Assessment of the Performance of Protein-ligand Scoring Functions Based on NMR Chemical Shift Perturbations

PubMed Central

Wang, Bing; Westerhoff, Lance M.; Merz, Kenneth M.

2008-01-01

We have generated docking poses for the FKBP-GPI complex using eight docking programs, and compared their scoring functions with scoring based on NMR chemical shift perturbations (NMRScore). Because the chemical shift perturbation (CSP) is exquisitely sensitive on the orientation of ligand inside the binding pocket, NMRScore offers an accurate and straightforward approach to score different poses. All scoring functions were inspected by their abilities to highly rank the native-like structures and separate them from decoy poses generated for a protein-ligand complex. The overall performance of NMRScore is much better than that of energy-based scoring functions associated with docking programs in both aspects. In summary, we find that the combination of docking programs with NMRScore results in an approach that can robustly determine the binding site structure for a protein-ligand complex, thereby, providing a new tool facilitating the structure-based drug discovery process. PMID:17867664

Distribution and magnitude of type I error of model-based multipoint lod scores: implications for multipoint mod scores.

PubMed

Xing, Chao; Elston, Robert C

2006-07-01

The multipoint lod score and mod score methods have been advocated for their superior power in detecting linkage. However, little has been done to determine the distribution of multipoint lod scores or to examine the properties of mod scores. In this paper we study the distribution of multipoint lod scores both analytically and by simulation. We also study by simulation the distribution of maximum multipoint lod scores when maximized over different penetrance models. The multipoint lod score is approximately normally distributed with mean and variance that depend on marker informativity, marker density, specified genetic model, number of pedigrees, pedigree structure, and pattern of affection status. When the multipoint lod scores are maximized over a set of assumed penetrances models, an excess of false positive indications of linkage appear under dominant analysis models with low penetrances and under recessive analysis models with high penetrances. Therefore, caution should be taken in interpreting results when employing multipoint lod score and mod score approaches, in particular when inferring the level of linkage significance and the mode of inheritance of a trait.

Dietary Toxicity Thresholds and Ecological Risks for Birds and Mammals Based on Species Sensitivity Distributions.

PubMed

Korsman, John C; Schipper, Aafke M; Hendriks, A Jan

2016-10-04

Species sensitivity distributions (SSDs) are commonly used in regulatory procedures and ecological risk assessments. Yet, most toxicity threshold and risk assessment studies are based on invertebrates and fish. In the present study, no observed effect concentrations (NOECs) specific to birds and mammals were used to derive SSDs and corresponding hazardous concentrations for 5% of the species (HC5 values). This was done for 41 individual substances as well as for subsets of substances aggregated based on their toxic Mode of Action (MoA). In addition, potential differences in SSD parameters (mean and standard deviation) were investigated in relation to MoA and end point (growth, reproduction, and survival). The means of neurotoxic and respirotoxic compounds were significantly lower than those of narcotics, whereas no differences were found between end points. The standard deviations of the SSDs were similar across MoA's and end points. Finally, the SSDs obtained were used in a case study by calculating Ecological Risks (ER) and multisubstance Potentially Affected Fractions of species (msPAF) based on 19 chemicals in 10 Northwestern European estuaries and coastal areas. The assessment showed that the risks were all below 2.6 × 10 -2 . However, the calculated risks underestimate the actual risks of chemicals in these areas because the potential impacts of substances that were not measured in the field or for which no SSD was available were not included in the risk assessment. The SSDs obtained can be used in regulatory procedures and for assessing the impacts of contaminants on birds and mammals from fish contaminants monitoring programs.

A Bootstrap Procedure of Propensity Score Estimation

ERIC Educational Resources Information Center

Bai, Haiyan

2013-01-01

Propensity score estimation plays a fundamental role in propensity score matching for reducing group selection bias in observational data. To increase the accuracy of propensity score estimation, the author developed a bootstrap propensity score. The commonly used propensity score matching methods: nearest neighbor matching, caliper matching, and…

Naive scoring of human sleep based on a hidden Markov model of the electroencephalogram.

PubMed

Yaghouby, Farid; Modur, Pradeep; Sunderam, Sridhar

2014-01-01

Clinical sleep scoring involves tedious visual review of overnight polysomnograms by a human expert. Many attempts have been made to automate the process by training computer algorithms such as support vector machines and hidden Markov models (HMMs) to replicate human scoring. Such supervised classifiers are typically trained on scored data and then validated on scored out-of-sample data. Here we describe a methodology based on HMMs for scoring an overnight sleep recording without the benefit of a trained initial model. The number of states in the data is not known a priori and is optimized using a Bayes information criterion. When tested on a 22-subject database, this unsupervised classifier agreed well with human scores (mean of Cohen's kappa > 0.7). The HMM also outperformed other unsupervised classifiers (Gaussian mixture models, k-means, and linkage trees), that are capable of naive classification but do not model dynamics, by a significant margin (p < 0.05).

Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

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

Harper, Bryan; Thomas, Dennis G.; Chikkagoudar, Satish

The integration of rapid assays, large data sets, informatics and modeling can overcome current barriers in understanding nanomaterial structure-toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality, were established at realistic exposure levels and used to develop a predictive model of nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both core composition and outermost surface chemistrymore » of nanomaterials. The resulting clusters guided the development of a predictive model of gold nanoparticle toxicity to embryonic zebrafish. In addition, our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. These findings reveal the need to expeditiously increase the availability of quantitative measures of nanomaterial hazard and broaden the sharing of that data and knowledge to support predictive modeling. In addition, research should continue to focus on methodologies for developing predictive models of nanomaterial hazard based on sub-lethal responses to low dose exposures.« less

Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

DOE PAGES

Harper, Bryan; Thomas, Dennis G.; Chikkagoudar, Satish; ...

2015-06-04

The integration of rapid assays, large data sets, informatics and modeling can overcome current barriers in understanding nanomaterial structure-toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality, were established at realistic exposure levels and used to develop a predictive model of nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both core composition and outermost surface chemistrymore » of nanomaterials. The resulting clusters guided the development of a predictive model of gold nanoparticle toxicity to embryonic zebrafish. In addition, our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. These findings reveal the need to expeditiously increase the availability of quantitative measures of nanomaterial hazard and broaden the sharing of that data and knowledge to support predictive modeling. In addition, research should continue to focus on methodologies for developing predictive models of nanomaterial hazard based on sub-lethal responses to low dose exposures.« less

Toxicity evaluation and prediction of toxic chemicals on activated sludge system.

PubMed

Cai, Bijing; Xie, Li; Yang, Dianhai; Arcangeli, Jean-Pierre

2010-05-15

The gaps of data for evaluating toxicity of new or overloaded organic chemicals on activated sludge system resulted in the requirements for methodology of toxicity estimation. In this study, 24 aromatic chemicals typically existed in the industrial wastewater were selected and classified into three groups of benzenes, phenols and anilines. Their toxicity on activated sludge was then investigated. Two indexes of IC(50-M) and IC(50-S) were determined respectively from the respiration rates of activated sludge with different toxicant concentration at mid-term (24h) and short-term (30min) time intervals. Experimental results showed that the group of benzenes was the most toxic, followed by the groups of phenols and anilines. The values of IC(50-M) of the tested chemicals were higher than those of IC(50-S). In addition, quantitative structure-activity relationships (QSARs) models developed from IC(50-M) were more stable and accurate than those of IC(50-S). The multiple linear models based on molecular descriptors and K(ow) presented better reliability than single linear models based on K(ow). Among these molecular descriptors, E(lumo) was the most important impact factor for evaluation of mid-term toxicity. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Identification of acute toxicants in New Bedford Harbor sediments

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

Ho, K.T.; McKinney, R.A.; Kuhn, A.

1997-03-01

New Bedford Harbor (NBH) is a marine Superfund site contaminated with high concentrations of polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and metals. Experiments were conducted to determine the causal toxic agent(s) in pore waters from New Bedford Harbor sediments to amphipods and mysid shrimp. Chemical manipulations to characterize toxicity revealed that pore-water toxicity was organic in nature. Fractionation and subsequent mass spectral identification of peaks in the toxic fraction indicated that PCBs. PAHs, and unknown compounds were present. Comparisons of PAH LC50s and PAH concentrations in this fraction indicated that the toxicity was not due to PAHs because themore » PAH concentrations were much lower than the reported PAH LC50s. One unknown peak was positively identified as bis(2-ethylhexyl) phthalate, and the other tentatively identified as pyrazole. Toxicity tests and comparison of toxicity in the blank and toxic fractions eliminated the two unknowns as toxic causal agents. The authors determined the range of PCB LC50s to fall between 10 and 110 ppb for Mysidopsis bahia and Ampelisca abdita. Concentrations of PCBs for the toxic fractions ranged from 12 to 27 ppb. This range falls within the observed PCB LC50s for M. bahia and A. abdita. Based upon these PCB concentrations, they concluded that PCBs were the acute toxic agents in NBH pore waters. Other compounds in the toxic fractions, or compounds that coeluted and were undistinguished from PCBs had minor contributions to the measured toxicity.« less

Integration of biological responses from a suite of bioassays for the Venice Lagoon (Italy) through sediment toxicity index - part A: development and comparison of two methodological approaches.

PubMed

Losso, Chiara; Novelli, Alessandra Arizzi; De Salvador, Davide; Ghetti, Pier Francesco; Ghirardini, Annamaria Volpi

2010-12-01

Marine and coastal quality assessment, based on test batteries involving a wide array of endpoints, organisms and test matrices, needs for setting up toxicity indices that integrate multiple toxicological measures for decision-making processes and that classify the continuous toxicity response into discrete categories according to the European Water Framework Directive. Two toxicity indices were developed for the lagoon environment such as the Venice Lagoon. Stepwise procedure included: the construction of a database that identified test-matrix pairs (indicators); the selection of a minimum number of ecotoxicological indicators, called toxicological core metrics (CMs-tox) on the basis of specific criteria; the development of toxicity scores for each CM-tox; the integration of the CMs-tox into two indices, the Toxicity Effect Index (TEI), based on the transformation of Toxic Unit (TU) data that were integrated as logarithmic sum, and the Weighted Average Toxicity Index (WATI), starting from toxicity classes integrated as weighted mean. Results from the indices are compared; advantages and drawbacks of both approaches are discussed. Copyright © 2010. Published by Elsevier Ltd.

Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

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

Grosshans, David R., E-mail: dgrossha@mdanderson.org; Zhu, X. Ronald; Melancon, Adam

2014-11-01

Purpose: To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. Methods and Materials: From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Results: Tenmore » patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. Conclusions: In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated

Visually scoring hirsutism

PubMed Central

Yildiz, Bulent O.; Bolour, Sheila; Woods, Keslie; Moore, April; Azziz, Ricardo

2010-01-01

BACKGROUND Hirsutism is the presence of excess body or facial terminal (coarse) hair growth in females in a male-like pattern, affects 5–15% of women, and is an important sign of underlying androgen excess. Different methods are available for the assessment of hair growth in women. METHODS We conducted a literature search and analyzed the published studies that reported methods for the assessment of hair growth. We review the basic physiology of hair growth, the development of methods for visually quantifying hair growth, the comparison of these methods with objective measurements of hair growth, how hirsutism may be defined using a visual scoring method, the influence of race and ethnicity on hirsutism, and the impact of hirsutism in diagnosing androgen excess and polycystic ovary syndrome. RESULTS Objective methods for the assessment of hair growth including photographic evaluations and microscopic measurements are available but these techniques have limitations for clinical use, including a significant degree of complexity and a high cost. Alternatively, methods for visually scoring or quantifying the amount of terminal body and facial hair growth have been in use since the early 1920s; these methods are semi-quantitative at best and subject to significant inter-observer variability. The most common visual method of scoring the extent of body and facial terminal hair growth in use today is based on a modification of the method originally described by Ferriman and Gallwey in 1961 (i.e. the mFG method). CONCLUSION Overall, the mFG scoring method is a useful visual instrument for assessing excess terminal hair growth, and the presence of hirsutism, in women. PMID:19567450

Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 2: reliability and application to multiple joints of a standardised consensus-based scoring system

PubMed Central

Terslev, Lene; Naredo, Esperanza; Aegerter, Philippe; Wakefield, Richard J; Backhaus, Marina; Balint, Peter; Bruyn, George A W; Iagnocco, Annamaria; Jousse-Joulin, Sandrine; Schmidt, Wolfgang A; Szkudlarek, Marcin; Conaghan, Philip G; Filippucci, Emilio

2017-01-01

Objectives To test the reliability of new ultrasound (US) definitions and quantification of synovial hypertrophy (SH) and power Doppler (PD) signal, separately and in combination, in a range of joints in patients with rheumatoid arthritis (RA) using the European League Against Rheumatisms–Outcomes Measures in Rheumatology (EULAR-OMERACT) combined score for PD and SH. Methods A stepwise approach was used: (1) scoring static images of metacarpophalangeal (MCP) joints in a web-based exercise and subsequently when scanning patients; (2) scoring static images of wrist, proximal interphalangeal joints, knee and metatarsophalangeal joints in a web-based exercise and subsequently when scanning patients using different acquisitions (standardised vs usual practice). For reliability, kappa coefficients (κ) were used. Results Scoring MCP joints in static images showed substantial intraobserver variability but good to excellent interobserver reliability. In patients, intraobserver reliability was the same for the two acquisition methods. Interobserver reliability for SH (κ=0.87) and PD (κ=0.79) and the EULAR-OMERACT combined score (κ=0.86) were better when using a ‘standardised’ scan. For the other joints, the intraobserver reliability was excellent in static images for all scores (κ=0.8–0.97) and the interobserver reliability marginally lower. When using standardised scanning in patients, the intraobserver was good (κ=0.64 for SH and the EULAR-OMERACT combined score, 0.66 for PD) and the interobserver reliability was also good especially for PD (κ range=0.41–0.92). Conclusion The EULAR-OMERACT score demonstrated moderate-good reliability in MCP joints using a standardised scan and is equally applicable in non-MCP joints. This scoring system should underpin improved reliability and consequently the responsiveness of US in RA clinical trials. PMID:28948984

Classification of Airflow Limitation Based on z-Score Underestimates Mortality in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Tejero, Elena; Prats, Eva; Casitas, Raquel; Galera, Raúl; Pardo, Paloma; Gavilán, Adelaida; Martínez-Cerón, Elisabet; Cubillos-Zapata, Carolina; Del Peso, Luis; García-Río, Francisco

2017-08-01

Global Lung Function Initiative recommends reporting lung function measures as z-score, and a classification of airflow limitation (AL) based on this parameter has recently been proposed. To evaluate the prognostic capacity of the AL classifications based on z-score or percentage predicted of FEV 1 in patients with chronic obstructive pulmonary disease (COPD). A cohort of 2,614 patients with COPD recruited outside the hospital setting was examined after a mean (± SD) of 57 ± 13 months of follow-up, totaling 10,322 person-years. All-cause mortality was analyzed, evaluating the predictive capacity of several AL staging systems. Based on Global Initiative for Chronic Obstructive Lung Disease guidelines, 461 patients (17.6%) had mild, 1,452 (55.5%) moderate, 590 (22.6%) severe, and 111 (4.2%) very severe AL. According to z-score classification, 66.3% of patients remained with the same severity, whereas 23.7% worsened and 10.0% improved. Unlike other staging systems, patients with severe AL according to z-score had higher mortality than those with very severe AL (increase of risk by 5.2 and 3.9 times compared with mild AL, respectively). The predictive capacity for 5-year survival was slightly higher for FEV 1 expressed as percentage of predicted than as z-score (area under the curve: 0.714-0.760 vs. 0.649-0.708, respectively). A severity-dependent relationship between AL grades by z-score and mortality was only detected in patients younger than age 60 years. In patients with COPD, the AL classification based on z-score predicts worse mortality than those based on percentage of predicted. It is possible that the z-score underestimates AL severity in patients older than 60 years of age with severe functional impairment.

Fluorescent sensor based models for the detection of environmentally-related toxic heavy metals.

PubMed

Rasheed, Tahir; Bilal, Muhammad; Nabeel, Faran; Iqbal, Hafiz M N; Li, Chuanlong; Zhou, Yongfeng

2018-02-15

The quest for industrial and biotechnological revolution has been contributed in increasing environmental contamination issues, worldwide. The controlled or uncontrolled release of hazardous pollutants from various industrial sectors is one of the key problems facing humanity. Among them, adverse influences of lead, cadmium, and mercury on human health are well known to cause many disorders like reproductive, neurological, endocrine system, and cardiovascular, etc. Besides their presence at lower concentrations, most of these toxic heavy metals are posing noteworthy toxicological concerns. In this context, notable efforts from various regulatory authorities, the increase in the concentration of these toxic heavy metals in the environment is of serious concern, so real-time monitoring is urgently required. This necessitates the exploration for novel and efficient probes for recognition of these toxic agents. Among various methodologies adopted for tailoring such probes, generally the methodologies, in which changes associated with spectral properties, are preferred for the deceptive ease in the recognition process. Accordingly, a promising modality has emerged in the form of radiometric and colorimetric monitoring of these toxic agents. Herein, we review fluorescent sensor based models and their potentialities to address the detection fate of hazardous pollutants for a cleaner environment. Second, recent advances regarding small molecule and rhodamine-based fluorescent sensors, radiometric and colorimetric probes are discussed. The information is also given on the photoinduced electron transfer (PET) mechanism, chelation enhancement fluorescence (CHEF) effect and spirocyclic ring opening mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study

PubMed Central

Gawron, Michal; Smith, Danielle M.; Peng, Margaret; Jacob, Peyton; Benowitz, Neal L.

2017-01-01

Introduction: Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. Methods: We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. Results: In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p < .05). After 1 week, the greatest percentage reductions in biomarkers levels were observed for metabolites of 1,3-butadiene, benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and 64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by 46% at week 1, and 34% at week 2. Conclusions: After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced. Implications: To our knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may

Scoring Methods for Building Genotypic Scores: An Application to Didanosine Resistance in a Large Derivation Set

PubMed Central

Houssaini, Allal; Assoumou, Lambert; Miller, Veronica; Calvez, Vincent; Marcelin, Anne-Geneviève; Flandre, Philippe

2013-01-01

Background Several attempts have been made to determine HIV-1 resistance from genotype resistance testing. We compare scoring methods for building weighted genotyping scores and commonly used systems to determine whether the virus of a HIV-infected patient is resistant. Methods and Principal Findings Three statistical methods (linear discriminant analysis, support vector machine and logistic regression) are used to determine the weight of mutations involved in HIV resistance. We compared these weighted scores with known interpretation systems (ANRS, REGA and Stanford HIV-db) to classify patients as resistant or not. Our methodology is illustrated on the Forum for Collaborative HIV Research didanosine database (N = 1453). The database was divided into four samples according to the country of enrolment (France, USA/Canada, Italy and Spain/UK/Switzerland). The total sample and the four country-based samples allow external validation (one sample is used to estimate a score and the other samples are used to validate it). We used the observed precision to compare the performance of newly derived scores with other interpretation systems. Our results show that newly derived scores performed better than or similar to existing interpretation systems, even with external validation sets. No difference was found between the three methods investigated. Our analysis identified four new mutations associated with didanosine resistance: D123S, Q207K, H208Y and K223Q. Conclusions We explored the potential of three statistical methods to construct weighted scores for didanosine resistance. Our proposed scores performed at least as well as already existing interpretation systems and previously unrecognized didanosine-resistance associated mutations were identified. This approach could be used for building scores of genotypic resistance to other antiretroviral drugs. PMID:23555613

Determining the Scoring Validity of a Co-Constructed CEFR-Based Rating Scale

ERIC Educational Resources Information Center

Deygers, Bart; Van Gorp, Koen

2015-01-01

Considering scoring validity as encompassing both reliable rating scale use and valid descriptor interpretation, this study reports on the validation of a CEFR-based scale that was co-constructed and used by novice raters. The research questions this paper wishes to answer are (a) whether it is possible to construct a CEFR-based rating scale with…

Ensemble-based docking: From hit discovery to metabolism and toxicity predictions

DOE PAGES

Evangelista, Wilfredo; Weir, Rebecca; Ellingson, Sally; ...

2016-07-29

The use of ensemble-based docking for the exploration of biochemical pathways and toxicity prediction of drug candidates is described. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials.

External validation of the simple clinical score and the HOTEL score, two scores for predicting short-term mortality after admission to an acute medical unit.

PubMed

Stræde, Mia; Brabrand, Mikkel

2014-01-01

Clinical scores can be of aid to predict early mortality after admission to a medical admission unit. A developed scoring system needs to be externally validated to minimise the risk of the discriminatory power and calibration to be falsely elevated. We performed the present study with the objective of validating the Simple Clinical Score (SCS) and the HOTEL score, two existing risk stratification systems that predict mortality for medical patients based solely on clinical information, but not only vital signs. Pre-planned prospective observational cohort study. Danish 460-bed regional teaching hospital. We included 3046 consecutive patients from 2 October 2008 until 19 February 2009. 26 (0.9%) died within one calendar day and 196 (6.4%) died within 30 days. We calculated SCS for 1080 patients. We found an AUROC of 0.960 (95% confidence interval [CI], 0.932 to 0.988) for 24-hours mortality and 0.826 (95% CI, 0.774-0.879) for 30-day mortality, and goodness-of-fit test, χ(2) = 2.68 (10 degrees of freedom), P = 0.998 and χ(2) = 4.00, P = 0.947, respectively. We included 1470 patients when calculating the HOTEL score. Discriminatory power (AUROC) was 0.931 (95% CI, 0.901-0.962) for 24-hours mortality and goodness-of-fit test, χ(2) = 5.56 (10 degrees of freedom), P = 0.234. We find that both the SCS and HOTEL scores showed an excellent to outstanding ability in identifying patients at high risk of dying with good or acceptable precision.

An illustrative overview of semi-quantitative MRI scoring of knee osteoarthritis: lessons learned from longitudinal observational studies.

PubMed

Roemer, F W; Hunter, D J; Crema, M D; Kwoh, C K; Ochoa-Albiztegui, E; Guermazi, A

2016-02-01

To introduce the most popular magnetic resonance imaging (MRI) osteoarthritis (OA) semi-quantitative (SQ) scoring systems to a broader audience with a focus on the most commonly applied scores, i.e., the MOAKS and WORMS system and illustrate similarities and differences. While the main structure and methodology of each scoring system are publicly available, the core of this overview will be an illustrative imaging atlas section including image examples from multiple OA studies applying MRI in regard to different features assessed, show specific examples of different grades and point out pitfalls and specifics of SQ assessment including artifacts, blinding to time point of acquisition and within-grade evaluation. Similarities and differences between different scoring systems are presented. Technical considerations are followed by a brief description of the most commonly utilized SQ scoring systems including their responsiveness and reliability. The second part is comprised of the atlas section presenting illustrative image examples. Evidence suggests that SQ assessment of OA by expert MRI readers is valid, reliable and responsive, which helps investigators to understand the natural history of this complex disease and to evaluate potential new drugs in OA clinical trials. Researchers have to be aware of the differences and specifics of the different systems to be able to engage in imaging assessment and interpretation of imaging-based data. SQ scoring has enabled us to explain associations of structural tissue damage with clinical manifestations of the disease and with morphological alterations thought to represent disease progression. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

An illustrative overview of semi-quantitative MRI scoring of knee osteoarthritis: Lessons learned from longitudinal observational studies

PubMed Central

Roemer, Frank W.; Hunter, David J.; Crema, Michel D.; Kwoh, C. Kent; Ochoa-Albiztegui, Elena; Guermazi, Ali

2015-01-01

Objective To introduce the most popular magnetic resonance imaging (MRI) osteoarthritis (OA) semi-quantitative (SQ) scoring systems to a broader audience with a focus on the most commonly applied scores, i.e. the MOAKS and WORMS system and illustrate similarities and differences. Design While the main structure and methodology of each scoring system are publicly available, the core of this overview will be an illustrative imaging atlas section including image examples from multiple osteoarthritis studies applying MRI in regard to different features assessed, show specific examples of different grades and point out pitfalls and specifics of SQ assessment including artifacts, blinding to time point of acquisition and within-grade evaluation. Results Similarities and differences between different scoring systems are presented. Technical considerations are followed by a brief description of the most commonly utilized SQ scoring systems including their responsiveness and reliability. The second part is comprised of the atlas section presenting illustrative image examples. Conclusions Evidence suggests that SQ assessment of OA by expert MRI readers is valid, reliable and responsive, which helps investigators to understand the natural history of this complex disease and to evaluate potential new drugs in OA clinical trials. Researchers have to be aware of the differences and specifics of the different systems to be able to engage in imaging assessment and interpretation of imaging-based data. SQ scoring has enabled us to explain associations of structural tissue damage with clinical manifestations of the disease and with morphological alterations thought to represent disease progression. PMID:26318656

A Community-Based Initiative to Reduce Children's Exposure to Toxics in Household Products

ERIC Educational Resources Information Center

Blackman, Anne Berlin; Luskin, Jack

2006-01-01

Purpose--The purpose of this paper is to explore the efficacy of a community-based outreach initiative, piloted in Worcester, Massachusetts, to reduce children's exposure to toxic chemicals in common household products by changing parental behavior regarding product purchase and use. Design/methodology/approach--The program model was based on the…

Comparison of Global and Mode of Action-Based Models for Aquatic Toxicity

EPA Science Inventory

The ability to estimate aquatic toxicity for a wide variety of chemicals is a critical need for ecological risk assessment and chemical regulation. The consensus in the literature is that mode of action (MOA) based QSAR (Quantitative Structure Activity Relationship) models yield ...

The mortality risk score and the ADG score: two points-based scoring systems for the Johns Hopkins aggregated diagnosis groups to predict mortality in a general adult population cohort in Ontario, Canada.

PubMed

Austin, Peter C; Walraven, Carl van

2011-10-01

Logistic regression models that incorporated age, sex, and indicator variables for the Johns Hopkins' Aggregated Diagnosis Groups (ADGs) categories have been shown to accurately predict all-cause mortality in adults. To develop 2 different point-scoring systems using the ADGs. The Mortality Risk Score (MRS) collapses age, sex, and the ADGs to a single summary score that predicts the annual risk of all-cause death in adults. The ADG Score derives weights for the individual ADG diagnosis groups. : Retrospective cohort constructed using population-based administrative data. All 10,498,413 residents of Ontario, Canada, between the age of 20 and 100 years who were alive on their birthday in 2007, participated in this study. Participants were randomly divided into derivation and validation samples. : Death within 1 year. In the derivation cohort, the MRS ranged from -21 to 139 (median value 29, IQR 17 to 44). In the validation group, a logistic regression model with the MRS as the sole predictor significantly predicted the risk of 1-year mortality with a c-statistic of 0.917. A regression model with age, sex, and the ADG Score has similar performance. Both methods accurately predicted the risk of 1-year mortality across the 20 vigintiles of risk. The MRS combined values for a person's age, sex, and the John Hopkins ADGs to accurately predict 1-year mortality in adults. The ADG Score is a weighted score representing the presence or absence of the 32 ADG diagnosis groups. These scores will facilitate health services researchers conducting risk adjustment using administrative health care databases.

A Comparison of Systemic Inflammation-Based Prognostic Scores in Patients on Regular Hemodialysis