Baseline Micronuclei Frequency in Children: Estimates from Meta- and Pooled Analyses

The number of studies evaluating the effect of environmental exposure to genotoxic agents in children has rapidly increased in the last few years. The frequency of micronuclei (MN) in peripheral blood lymphocytes determined with the cytokinesis block assay is among the most popular biomarkers used for this purpose, although large inter- and intralaboratory variability of this end point has been observed in population studies. The availability of reference measures is therefore necessary for laboratories to validate protocols and analytical procedures, and for molecular epidemiologists, as well, to estimate the statistical power of studies and to assess the quality of data. In this article, we provide estimates of the baseline frequency of MN in children, conducting a meta-analysis of MN frequency reported by field studies in children and a pooled analysis of individual data [available from published studies and from the Human Micronucleus International Collaborative Study (HUMN) database]. Thirteen articles were selected for meta-analysis, and individual data included in the pooled analysis were retrieved from the databases of 12 laboratories. Overall means of 4.48 [95% confidence interval (CI), 3.35–5.98] and 5.70 (95% CI, 4.29–7.56) MN per 1,000 binucleated cells were estimated by the meta- and pooled analysis, respectively. A clear effect of age was detected, even within the restricted range of pediatric age considered, with significantly lower frequency values in newborns. No influence of sex was found. The study showed the advantage of using data from large collaborative studies and suggested a synergistic use of meta- and pooled analysis

LSTM neural networks: Input to state stability and probabilistic safety verification

The goal of this paper is to analyze Long Short Term Memory (LSTM) neural networks from a dynamical system perspective. The classical recursive equations describing the evolution of LSTM can be recast in state space form, resulting in a time-invariant nonlinear dynamical system. A sufficient condition guaranteeing the Input-to-State (ISS) stability property of this class of systems is provided. The ISS property entails the boundedness of the output reachable set of the LSTM. In light of this result, a novel approach for the safety verification of the network, based on the Scenario Approach, is devised. The proposed method is eventually tested on a pH neutralization process

Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries

Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965–2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07–1.60] and in the high (RR = 1.41; 95% CI = 1.16–1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34–3.68). The strongest association was found for stomach cancer [RRmedium = 1.17 (95% CI = 0.37–3.70), RRhigh = 3.13 (95% CI = 1.17–8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type

Mumificaçao fetal em suínos associada à toxoplasmose.

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Bayes and Big Data: The Consensus Monte Carlo Algorithm

A useful definition of ‘big data’ is data that is too big to process comfortably on a single machine, either because of processor, memory, or disk bottlenecks. Graphics processing units can alleviate the processor bottleneck, but memory or disk bottlenecks can only be eliminated by splitting data across multiple machines. Communication between large numbers of machines is expensive (regardless of the amount of data being communicated), so there is a need for algorithms that perform distributed approximate Bayesian analyses with minimal communication. Consensus Monte Carlo operates by running a separate Monte Carlo algorithm on each machine, and then averaging individual Monte Carlo draws across machines. Depending on the model, the resulting draws can be nearly indistinguishable from the draws that would have been obtained by running a single-machine algorithm for a very long time. Examples of consensus Monte Carlo are shown for simple models where single-machine solutions are available, for large single-layer hierarchical models, and for Bayesian additive regression trees (BART)

Emissions generated by sugarcane burning promote genotoxicity in rural workers: a case study in Barretos, Brazil

Background: To determine the possible genotoxic effect of exposure to the smoke generated by biomass burning on workers involved in manual sugar cane harvesting. Methods: The frequency of micronuclei in exfoliated buccal cells and peripheral blood lymphocytes was determined in sugarcane workers in the Barretos region of Brazil, during the harvest season and compared to a control population, comprised of administrative employees of Barretos Cancer Hospital. Results: The frequency of micronuclei was higher in the sugar cane workers. The mean frequency in blood lymphocytes (micronuclei/1000 cells) in the test group was 8.22 versus 1.27 in the control group. The same effect was observed when exfoliated buccal cells were considered (22.75 and 9.70 micronuclei/1000 cells for sugar cane workers and controls, respectively). Conclusion: Exposure to emissions produced by the burning of sugar cane during harvesting induces genomic instability in workers, indicating the necessity of adopting more advanced techniques of harvesting sugar cane to preserve human health.We thank the Researcher Support Center of Barretos Cancer Hospital, especially the statistician Zanardo C. for assisting in the statistical analysis. We thank Oliveira R. for technical support, and we acknowledge financial support from FAPESP Proc. 2010/10192-6

B Lymphocytes as Targets of the Immunomodulatory Properties of Human Amniotic Mesenchymal Stromal Cells

Mesenchymal stromal cells (MSC) from the amniotic membrane of human term placenta (hAMSC), and the conditioned medium generated from their culture (CM-hAMSC) offer significant tools for their use in regenerative medicine mainly due to their immunomodulatory properties. Interestingly, hAMSC and their CM have been successfully exploited in preclinical disease models of inflammatory and autoimmune diseases where depletion or modulation of B cells have been indicated as an effective treatment, such as inflammatory bowel disease, lung fibrosis, would healing, collagen-induced arthritis, and multiple sclerosis. While the interactions between hAMSC or CM-hAMSC and T lymphocytes, monocytes, dendritic cells, and macrophages has been extensively explored, how they affect B lymphocytes remains unclear. Considering that B cells are key players in the adaptive immune response and are a central component of different diseases, in this study we investigated the in vitro properties of hAMSC and CM-hAMSC on B cells. We provide evidence that both hAMSC and CM-hAMSC strongly suppressed CpG-activated B-cell proliferation. Moreover, CM-hAMSC blocked B-cell differentiation, with an increase of the proportion of mature B cells, and a reduction of antibody secreting cell formation. We observed the strong inhibition of B cell terminal differentiation into CD138+ plasma cells, as further shown by a significant decrease of the expression of interferon regulatory factor 4 (IRF-4), PR/SET domain 1(PRDM1), and X-box binding protein 1 (XBP-1) genes. Our results point out that the mechanism by which CM-hAMSC impacts B cell proliferation and differentiation is mediated by secreted factors, and prostanoids are partially involved in these actions. Factors contained in the CM-hAMSC decreased the CpG-uptake sensors (CD205, CD14, and TLR9), suggesting that B cell stimulation was affected early on. CM-hAMSC also decreased the expression of interleukin-1 receptor-associated kinase (IRAK)-4, consequently inhibiting the entire CpG-induced downstream signaling pathway. Overall, these findings add insight into the mechanism of action of hAMSC and CM-hAMSC and are useful to better design their potential therapeutic application in B-cell mediated diseases

Association between Frequency of Chromosomal Aberrations and Cancer Risk Is Not Influenced by Genetic Polymorphisms in GSTM1 and GSTT1

To evaluate the role of polymorphisms in glutathione S-transferase M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk. A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analysed by setting up a Bayesian model which included prior information about cancer risk by CA frequency