Biomarkers in monitoring - a review

Årsliste 2006Biological effects are increasingly used to monitor impacts of contaminants in marine ecosystems. Biomarkers have been defined as ”biochemical, cellular, physiological or behavioural variations in the tissue or body fluids or at the level of whole organism that provide evidence of exposure to chemical pollutants, and may also indicate a toxic effect”. The biomarkers reviewed here were PAH bile metabolites, cytochrome P4501A, glutathione S-transferase, markers for DNA damage (adducts, alkaline unwinding, Comet assay), micronucleus formation, peroxisomal proliferation, acetyl cholinesterase inhibition, metallothionein, vitellogenin and delta-aminolevulinic acid dehydratase. Focus for the review was dose-response relationships, confounding factors, links to population effects, baseline values, assessment criteria and quality assurance for the relevant biomarker. Whereas correlative links to population-relevant effects have been found for some biomarkers, e.g. biomarkers for DNA damage, most biomarkers are generally more useful as markers for possible impacts elsewhere in ecosystems.OL

Enabling Semantic Data Access for Toxicological Risk Assessment

Experimental effort and animal welfare are concerns when exploring the effects a compound has on an organism. Appropriate methods for extrapolating chemical effects can further mitigate these challenges. In this paper we present the efforts to (i) (pre)process and gather data from public and private sources, varying from tabular files to SPARQL endpoints, (ii) integrate the data and represent them as a knowledge graph with richer semantics. This knowledge graph is further applied to facilitate the retrieval of the relevant data for a ecological risk assessment task, extrapolation of effect data, where two prediction techniques are developed

Deaths due to differentiated thyroid cancer: A 46-year perspective

From 1940 to 1986, a total of 798 patients were treated for differentiated thyroid carcinoma. One hundred and seventy-two patients died during the follow-up period: 42 (24.4%) patients from thyroid cancer, 14 (8.1%) from other causes with extensive thyroid cancer present, 75 (43.6%) with no thyroid cancer, and 41 (23.8%) with an unknown status of thyroid cancer . Of the 42 patients dying due to thyroid cancer, 15 were male and 27, female. Mean age at diagnosis was 48.3±17.7 years with one-third of patients age 45 or younger at the time of the initial diagnosis. The primary tumors were large (>4 cm) and 59.5% of the patients had local invasion and/or cervical metastasis. Distant metastases were present in 9 (21.4%) patients at the time of diagnosis . Surgical therapy included total thyroidectomy (72.1%) and limited or radical neck dissection (69.4%). Radioactive iodine ( 131 I) was used to treat residual cancer and/or distant metastasis in 73.8% of the patients. External radiation therapy was used to treat locally advanced or recurrent disease in 52.3% of the patients. Distant metastases and local recurrence were identified earlier in patients with follicular thyroid cancer whose survival time and disease-free interval were significantly shorter ( p < 0.001) than that of patients with papillary neoplasms. However, the survival and disease-free intervals were often very long in both papillary and follicular thyroid cancer deaths . Onset of differentiated thyroid cancer before the age of 40 years does not preclude serious sequelae and death. Since no known histopathologic features can consistently predict outcome, we continue to advocate aggressive treatment of all patients with differentiated thyroid cancer . Entre 1940 et 1986, 798 patients au total ont été traités pour un cancer différencié de la thyroïde. Cent-soixant-douze patients sont morts par la suite: 42 (24.4%) de leur cancer, 14 (8.1%) d'une autre cause alors que des signes d'extension du cancer étaient présents, 75 (43.6%) d'une autre cause sans signe de cancer, et 41 (23.8%) sans qu'on ait pu connaître le stade du cancer. Des 42 patients morts de leur cancer, il y avait 15 hommes et 27 femmes. L'âge moyen au moment du diagnostic était de 48.3±17.7 ans: un tiers des patients avait 45 ans ou moins au moment du diagnostic. Les tumeurs primitives avaient plus de 4 cm et 59.5% des patients présentaient un envahissement local et/ou une métastase cervicale. Les métastases à distance ont été détectées chez 9 (21.4%) patients au moment du diagnostic. Une thyroïdectomie totale a été effectuée chez 72.1% des patients, associée à un curage cervical limité ou radical chez 69.4% des patients. Chez 73.8% des patients on a traité le tissu cancéreux résiduel et/ou des métastases à distance par de l'I 131. La radiothérapie a été utilisée pour traiter les patients présentant une extension importante ou une récidive chez 52.3% des patients. Des métastases à distance et des récidives ont été identifiées précocement chez les patients ayant un cancer folliculaire. Dans ce groupe de patients, la survie et l'intervalle de temps sans maladie étaient significativement plus courts ( p <0.001) que chez les patients ayant un cancer papillaire. Il faut cependant noter que la survie et l'intervalle de temps sans maladie étaient très longs dans les 2 groupes de patients. La découverte d'un cancer différencié de la thyroïde avant l'âge de 40 ans n'est pas un facteur pronostique particulier. Puisqu'il n'y pas de facteur histologique permettant de prévoir l'évolution, nous continuons de préconiser un traitement agressif chez tout patient présentant un cancer différencié de la thyroïde. En el período 1940–1986, un total de 798 pacientes recibieron tratamiento para carcinoma tiroideo; 172 murieron en el curso del seguimiento: 42 (24.4%) por cancer tiroideo, 14 (8.1%) por otras causas pero con presencia de extenso cáncer tiroideo, 75 (43.6%) libres de cáncer tiroideo, y 41 (23.8%) con estado desconocido en cuanto al cancer tiroideo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41283/1/268_2005_Article_BF01655866.pd

Prediction of Adverse Biological Effects of Chemicals Using Knowledge Graph Embeddings

We have created a knowledge graph based on major data sources used in ecotoxicological risk assessment. We have applied this knowledge graph to an important task in risk assessment, namely chemical effect prediction. We have evaluated nine knowledge graph embedding models from a selection of geometric, decomposition, and convolutional models on this prediction task. We show that using knowledge graph embeddings can increase the accuracy of effect prediction with neural networks. Furthermore, we have implemented a fine-tuning architecture which adapts the knowledge graph embeddings to the effect prediction task and leads to a better performance. Finally, we evaluate certain characteristics of the knowledge graph embedding models to shed light on the individual model performance

Glycotope structures and intramolecular affinity factors of plant lectins for Tn/T antigens

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Interacting mindreaders

Could interacting mindreaders be in a position to know things which they would be unable to know if they were manifestly passive observers? This paper argues that they could. Mindreading is sometimes reciprocal: the mindreader's target reciprocates by taking the mindreader as a target for mindreading. The paper explains how such reciprocity can significantly narrow the range of possible interpretations of behaviour where mindreaders are, or appear to be, in a position to interact. A consequence is that revisions and extensions are needed to standard theories of the evidential basis of mindreading. The view also has consequences for understanding how abilities to interact combined with comparatively simple forms of mindreading may explain the emergence, in evolution or development, of sophisticated forms of social cognition