A simulation model for diarrhoea and other common recurrent infections: a tool for exploring epidemiological methods

The measurement and analysis of common recurrent conditions such as diarrhoea, respiratory infections or fever pose methodological challenges with regard to case definition, disease surveillance and statistical analysis. In this paper we describe a flexible and robust model that can generate simulated longitudinal datasets for a range of recurrent infections, reflecting the stochastic processes that underpin the data collected in the field. It can be used to evaluate and compare alternative disease definitions, surveillance strategies and statistical methods under ‘controlled conditions’. Parameters in the model include: characterizing the distributions of the individual disease incidence and the duration of disease episodes; allowing the average disease duration to depend on an individual's number of episodes (simulating a correlation between incidence and duration); making the individual risk of disease depend on the occurrence of previous episodes (simulating autocorrelation of successive episodes); finally, incorporating seasonal variation of disease

First report of eprinomectin-resistant isolates of Haemonchus contortus in 5 dairy sheep farms from the Pyrénées Atlantiques département in France

Infection of sheep by gastrointestinal nematodes (GIN) in pastoral systems such as those found in the South Western area of France, the Pyrénées Atlantiques, is one of the main reasons for economic loss and degradation of their welfare. In the present study, the efficacy of eprinomectin (EPN) was monitored on farms from this area following suspicion of lack of anthelmintic efficacy. Suspicions were raised by veterinarians, based on clinical signs ranging from milk and body condition loss, to anaemia, and mortality. Resistance was evaluated according to the World Association for the Advancement for Veterinary Parasitology (WAAVP) guidelines using fecal egg count reduction tests reinforced by individual analysis of drug concentration in the serum of all treated ewes by high-performance liquid chromatography (HPLC). EPN was administered by subcutaneous (SC) and topical (T) route according to manufacturer's requirements, as well as by the oral route (O) with the topical solution according to off-labelled practices in the field. For the first time in France, the presence of resistant isolates of Haemonchus contortus to EPN was observed in 5 dairy sheep farms. The HPLC dosages showed exposure of worms to concentrations compatible with anthelmintic activity for animals treated by the SC and O routes. By contrast, they showed under exposure to the drug of most individuals treated by the T route. EPN is the only null milk withdrawal anthelmintic molecule currently available. The presence of resistant isolates of the pathogenic H. contortus to EPN in this important dairy region requires an urgent change in grazing, and sometimes production, systems

Sampling strategies to measure the prevalence of common recurrent infections in longitudinal studies

<p>Abstract</p> <p>Background</p> <p>Measuring recurrent infections such as diarrhoea or respiratory infections in epidemiological studies is a methodological challenge. Problems in measuring the incidence of recurrent infections include the episode definition, recall error, and the logistics of close follow up. Longitudinal prevalence (LP), the proportion-of-time-ill estimated by repeated prevalence measurements, is an alternative measure to incidence of recurrent infections. In contrast to incidence which usually requires continuous sampling, LP can be measured at intervals. This study explored how many more participants are needed for infrequent sampling to achieve the same study power as frequent sampling.</p> <p>Methods</p> <p>We developed a set of four empirical simulation models representing low and high risk settings with short or long episode durations. The model was used to evaluate different sampling strategies with different assumptions on recall period and recall error.</p> <p>Results</p> <p>The model identified three major factors that influence sampling strategies: (1) the clustering of episodes in individuals; (2) the duration of episodes; (3) the positive correlation between an individual's disease incidence and episode duration. Intermittent sampling (e.g. 12 times per year) often requires only a slightly larger sample size compared to continuous sampling, especially in cluster-randomized trials. The collection of period prevalence data can lead to highly biased effect estimates if the exposure variable is associated with episode duration. To maximize study power, recall periods of 3 to 7 days may be preferable over shorter periods, even if this leads to inaccuracy in the prevalence estimates.</p> <p>Conclusion</p> <p>Choosing the optimal approach to measure recurrent infections in epidemiological studies depends on the setting, the study objectives, study design and budget constraints. Sampling at intervals can contribute to making epidemiological studies and trials more efficient, valid and cost-effective.</p

What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

Stilbenes are naturally occurring phytoalexins that generally exist as their more stable E isomers. The most well known natural stilbene is resveratrol (Res), firstly isolated in 1939 from roots of Veratrum grandiflorum (white hellebore) (1) and since then found in various edible plants, notably in Vitis vinifera L. (Vitaceae) (2). The therapeutic potential of Res covers a wide range of diseases, and multiple beneficial effects on human health such as antioxidant, anti-inflammatory and anti-cancer activities have been suggested based on several in vitro and animal studies (3). In particular, Res has been reported to be an inhibitor of carcinogenesis at multiple stages via its ability to inhibit cyclooxygenase, and is an anticancer agent with a role in antiangiogenesis (4). Moreover, both in vitro and in vivo studies showed that Res induces cell cycle arrest and apoptosis in tumor cells (4). However, clinical studies in humans evidenced that Res is rapidly absorbed after oral intake, and that the low level observed in the blood stream is caused by a fast conversion into metabolites that are readily excreted from the body (5). Thus, considerable efforts have gone in the design and synthesis of Res analogues with enhanced metabolic stability. Considering that reduced Res (dihydro- resveratrol, D-Res) conjugates may account for as much as 50% of an oral Res dose (5), and that D-Res has a strong proliferative effect on hormone-sensitive cancer cell lines such as breast cancer cell line MCF7 (6), we recently devoted our synthetic efforts to the preparation of trans-restricted analogues of Res in which the E carbon-carbon double bond is embedded into an imidazole nucleus. To keep the trans geometry, the two aryl rings were linked to the heteroaromatic core in a 1,3 fashion. Based on this design, we successfully prepared a variety of 1,4-, 2,4- and 2,5-diaryl substituted imidazoles including Res analogues 1, 2 and 3, respectively, by procedures that involve transition metal-catalyzed Suzuki-Miyaura cross-coupling reactions and highly selective N-H or C-H direct arylation reactions as key synthetic steps. The anticancer activity of compounds 1–3 was evaluated against the 60 human cancer cell lines panel of the National Cancer Institute (NCI, USA). The obtained results, that will be showed and discussed along with the protocols developed for the preparation of imidazoles 1–3, confirmed that a structural optimization of Res may provide analogues with improved potency in inhibiting the growth of human cancer cell lines in vitro when compared to their natural lead. (1) Takaoka,M.J.Chem.Soc.Jpn.1939,60,1090-1100. (2) Langcake, P.; Pryce, R. J. Physiological. Plant Patology 1976, 9, 77-86. (3) Vang, O.; et al. PLoS ONE 2011, 6, e19881. doi:10.1371/journal.pone.0019881 (4) Kraft, T. E.; et al. Critical Reviews in Food Science and Nutrition 2009, 49, 782-799. (5) Walle, T. Ann. N.Y. Acad. Sci. 2011, 1215, 9-15. doi: 10.1111/j.1749-6632.2010.05842.x (6) Gakh,A.A.;etal.Bioorg.Med.Chem.Lett.2010,20,6149-6151

Quantification and restoration of extensional deformation along the Western Iberia and Newfoundland rifted margins.

International audienc

Hyper-extended crust in the south atlantic: In search of a model.

International audienc

Réactions croisées entre pollen et graine de Brassica napus : implication des allergènes non hydrosolubles

International audienc