Automated read-across workflow for predicting acute oral toxicity: I. The decision scheme in the QSAR toolbox.

A decision-scheme outlining the steps for identifying the appropriate chemical category and subsequently appropriate tested source analog(s) for data gap filling of a target chemical by read-across is described. The primary features used in the grouping of the target chemical with source analogues within a database of 10,039 discrete organic substances include reactivity mechanisms associated with protein interactions and specific-acute-oral-toxicity-related mechanisms (e.g., mitochondrial uncoupling). Additionally, the grouping of chemicals making use of the in vivo rat metabolic simulator and neutral hydrolysis. Subsequently, a series of structure-based profilers are used to narrow the group to the most similar analogues. The scheme is implemented in the OECD QSAR Toolbox, so it automatically predicts acute oral toxicity as the rat oral LD50 value in log [1/mol/kg]. It was demonstrated that due to the inherent variability in experimental data, classification distribution should be employed as more adequate in comparison to the exact classification. It was proved that the predictions falling in the adjacent GSH categories to the experimentally-stated ones are acceptable given the variation in experimental data. The model performance estimated by adjacent accuracy was found to be 0.89 and 0.54 while based on R2. The mechanistic and predictive coverages were >0.85.

Influenza surveillance on 'foie gras' duck farms in Bulgaria, 2008-2012.

OBJECTIVES: Ducks can shed and spread influenza A viruses (IAVs) while showing no disease signs. Our objective was to clarify the role of 'foie gras' ducks in the circulation of IAVs in Bulgaria. METHODS: Monthly avian influenza surveillance was conducted on 63 'foie gras' duck farms, 52 of which were surveyed throughout the study between November 2008 and April 2012. Virologic and serologic samples were collected and tested. During this time, wild bird samples were collected at major wild bird-resting areas near the Black Sea coast and Danube River. RESULTS: The study showed high isolation frequency of low-pathogenicity avian influenza viruses. In the raising population (<75 days old), subtypes H3, H4, and H6 were detected monthly and H5 LPAIV, sporadically. Different subtypes (H1, H10, H11) were isolated from the fattening premises (75- to 100-day-old ducks), suggesting different routes of introduction. Only 6 of the 52 farms that were surveyed both virologically and serologically were influenza-free throughout the study, possibly due to higher biosecurity measures implemented. No evidence of direct transmission of IAV from wild birds was found. Wild bird surveillance showed low isolation frequency of IAV. IAV prevalence of 0·55% for migratory ducks and 0·53% for migratory geese was estimated in November-December 2011 and January-February 2012, respectively, at two ornithologically important locations near the Black Sea coast. CONCLUSIONS: The 'foie gras' duck farms in Bulgaria are an optimal niche where Eurasian-like IAVs are maintained and reassorted unapparent to farmers and veterinarians.

Computer-aided detection of lung nodules via 3D fast radial transform, scale space representation, and Zernike MIP classification.

PURPOSE: The authors presented a novel system for automated nodule detection in lung CT exams. METHODS: The approach is based on (1) a lung tissue segmentation preprocessing step, composed of histogram thresholding, seeded region growing, and mathematical morphology; (2) a filtering step, whose aim is the preliminary detection of candidate nodules (via 3D fast radial filtering) and estimation of their geometrical features (via scale space analysis); and (3) a false positive reduction (FPR) step, comprising a heuristic FPR, which applies thresholds based on geometrical features, and a supervised FPR, which is based on support vector machines classification, which in turn, is enhanced by a feature extraction algorithm based on maximum intensity projection processing and Zernike moments. RESULTS: The system was validated on 154 chest axial CT exams provided by the lung image database consortium public database. The authors obtained correct detection of 71% of nodules marked by all radiologists, with a false positive rate of 6.5 false positives per patient (FP/patient). A higher specificity of 2.5 FP/patient was reached with a sensitivity of 60%. An independent test on the ANODE09 competition database obtained an overall score of 0.310. CONCLUSIONS: The system shows a novel approach to the problem of lung nodule detection in CT scans: It relies on filtering techniques, image transforms, and descriptors rather than region growing and nodule segmentation, and the results are comparable to those of other recent systems in literature and show little dependency on the different types of nodules, which is a good sign of robustness.

Toxic epidermal necrolysis as a dermatological manifestation of drug hypersensitivity syndrome.

Drug hypersensitivity syndrome (DHS) is believed to be an adverse idiosyncratic drug reaction associated mainly with administration of aromatic antiepileptic drugs, such as phenytoin, carbamazepine, phenobarbital, lamotrigine. The syndrome is defined by the clinical triad of fever, skin rash and internal organ involvement and can be life-threatening condition. We describe three patients treated in our institution. The first was a 32-year-old man who developed toxic epidermal necrolysis (TEN) with pulmonary and liver involvement after initiation of lamotrigine therapy for concomitant epilepsy. The second 32-year-old man was treated with salazopyrine and omeprazole in order to relief the symptoms of inflammatory bowel disease, but as a result developed toxic epidermal necrolysis with elevated liver enzymes. The third patient was a 28-year-old man with long history of alcohol abuse who began treatment with carbamazepine and a few days later he was admitted to the clinic with symptoms of severe disseminated skin rash. The patients had peripheral eosinophilia. All the patients needed urgent life-saving therapy, intensive care and nursing. The culprit drug was discontinued and prompt systemic therapy with corticosteroids at an initial dose of 2 mg/kg/d and with broad spectrum antibiotics was started. Topical therapy included spraying Avène thermal water and local antiseptics. Resolution and epithelization of skin erosions were observed in about 4 weeks after the initiation of the therapy. Medications can give rise to certain adverse reactions including serious cutaneous and systemic involvement. TEN is a rare complication of DHS. Patients who develop DHS need optimal and adequate treatment. The concomitant use of corticosteroids and broad spectrum systemic antibiotics is essential. The local therapy plays an important part in relieving symptoms and should consist of mild preparations with minimally sensitizing potential.