Bayesian inference for spatio-temporal stochastic transmission of plant disease in the presence of roguing: A case study to characterise the dispersal of Flavescence dorée.

Estimating the distance at which pathogens disperse from one season to the next is crucial for designing efficient control strategies for invasive plant pathogens and a major milestone in the reduction of pesticide use in agriculture. However, we still lack such estimates for many diseases, especially for insect-vectored pathogens, such as Flavescence dorée (FD). FD is a quarantine disease threatening European vineyards. Its management is based on mandatory insecticide treatments and the removal of infected plants identified during annual surveys. This paper introduces a general statistical framework to model the epidemiological dynamics of FD in a mechanistic manner that can take into account missing hosts in surveyed fields (resulting from infected plant removals). We parameterized the model using Markov chain Monte Carlo (MCMC) and data augmentation from surveillance data gathered in Bordeaux vineyards. The data mainly consist of two snapshot maps of the infectious status of all the plants in three adjacent fields during two consecutive years. We demonstrate that heavy-tailed dispersal kernels best fit the spread of FD and that on average, 50% (resp. 80%) of new infection occurs within 10.5 m (resp. 22.2 m) of the source plant. These values are in agreement with estimates of the flying capacity of Scaphoideus titanus, the leafhopper vector of FD, reported in the literature using mark-capture techniques. Simulations of simple removal scenarios using the fitted model suggest that cryptic infection hampered FD management. Future efforts should explore whether strategies relying on reactive host removal can improve FD management.

Evidence-based controls for epidemics using spatio-temporal stochastic models in a Bayesian framework.

The control of highly infectious diseases of agricultural and plantation crops and livestock represents a key challenge in epidemiological and ecological modelling, with implemented control strategies often being controversial. Mathematical models, including the spatio-temporal stochastic models considered here, are playing an increasing role in the design of control as agencies seek to strengthen the evidence on which selected strategies are based. Here, we investigate a general approach to informing the choice of control strategies using spatio-temporal models within the Bayesian framework. We illustrate the approach for the case of strategies based on pre-emptive removal of individual hosts. For an exemplar model, using simulated data and historic data on an epidemic of Asiatic citrus canker in Florida, we assess a range of measures for prioritizing individuals for removal that take account of observations of an emerging epidemic. These measures are based on the potential infection hazard a host poses to susceptible individuals (hazard), the likelihood of infection of a host (risk) and a measure that combines both the hazard and risk (threat). We find that the threat measure typically leads to the most effective control strategies particularly for clustered epidemics when resources are scarce. The extension of the methods to a range of other settings is discussed. A key feature of the approach is the use of functional-model representations of the epidemic model to couple epidemic trajectories under different control strategies. This induces strong positive correlations between the epidemic outcomes under the respective controls, serving to reduce both the variance of the difference in outcomes and, consequently, the need for extensive simulation.

Quaternized carbon dot-modified graphene oxide for selective cell labelling--controlled nucleus and cytoplasm imaging.

Cationic quaternized carbon dots (QCDs) and anionic graphene oxide sheets (GO) are combined via non-covalent interactions following a self-assembly pathway to form highly biocompatible and fluorescent hybrid materials. These hybrids act as selective probes with controlled labelling of the cell nucleus or cytoplasm depending on the QCD loading.

LmbJ and LmbIH protein levels correlate with lincomycin production in Streptomyces lincolnensis.

AIMS: To demonstrate the expression of two overlapping genes lmbJ and lmbIH in Streptomyces lincolnensis and to document LmbJ and LmbIH protein levels during the lincomycin production phase. To analyse presumable function of the LmbIH protein. METHODS AND RESULTS: Lincomycin production was monitored by thin-layer chromatography, proteins LmbJ and LmbIH were assayed in the cell-free extracts of S. lincolnensis by immunodetection. LmbJ occurred at stable level (2-4 mg x g(-1) of total proteins) for a long time period (36-96 h of cultivation) covering the whole production phase. This fairly corresponds to the catalytic function of the protein in the antibiotic biosynthesis (N-demethyllincomycin methyltransferase). On the contrary, LmbIH reached the detectable level (0.1 and 0.7 mg x g(-1)) just for a short period at 60-72 h. CONCLUSIONS: The absence of LmbIH protein at a detectable level during the major part of the antibiotic production phase casts doubt on its possible catalytic function. Rather a different connection with the final biosynthetic steps, e.g. regulatory, can be envisaged. SIGNIFICANCE AND IMPACT OF THE STUDY: Expression of a newly found putative regulatory gene was demonstrated during production of industrial antibiotic, lincomycin.

Putative lmbI and lmbH genes form a single lmbIH ORF in Streptomyces lincolnensis type strain ATCC 25466.

The lincomycin-production gene cluster of the industrial overproduction strain Streptomyces lincolnensis 78-11 has been sequenced (Peschke et al. 1995) and twenty-seven putative open reading frames with biosynthetic or regulatory functions (lmb genes) identified. Two distinct hypothetical genes, lmbI and lmbH, were found downstream of the lmbJ gene, coding for LmbJ protein, which is believed to participate in the last lincomycin biosynthetic step, i.e. conversion of N-demethyllincomycin (NDL) to lincomycin. In the present study, we demonstrate the presence of a single larger open reading frame, called lmbIH, in the lincomycin low-production type strain Streptomyces lincolnensis ATCC 25466, instead of two smaller lmbI and lmbH genes. The product, LmbIH, is a protein of an unknown function and is homologous with the T1dD protein family. Escherichia coli T1dD protein was previously shown to be involved in the control of DNA gyrase by LetD protein. Moreover, our experiments indicate co-regulation of lmbJ and lmbIH expression. This translation coupling probably reflects an eight nucleotide overlap between the lmbJ and lmbIH genes, as well as the lack of a Shine-Dalgarno sequence upstream of the lmbIH gene.

[Treatment of Helicobacter pylori infection in patients with duodenal ulcer: a cost-benefit study]. / Tratamiento de la infección por Helicobacter pylori en pacientes con úlcera duodenal: estudio de costo-beneficio.

BACKGROUND: Epidemiological differences suggest that treatments for H. pylori eradication should be locally validated. AIM: To perform a cost benefit study of different treatment options for H. pylori infection. PATIENTS AND METHODS: One hundred and sixty-seven patients with active duodenal ulcer and H. pylori infection who completed a 2-week treatment with one of the following regimens were included: famotidine plus amoxycillin plus metronidazole (FAM), omeprazole plus amoxycillin plus tinidazole (OAT) or lansoprazole plus clarithromycin plus amoxycillin in 3 (LAC1) or 2 (LAC2) daily doses. We compared efficacy, adverse effects and cost. RESULTS: Eradication rate was 74.6, 72.9, 96.4 y 91.7% for FAM, OAT, LAC1 and LAC2 respectively (p < 0.05). Direct cost ranged from US$ 50 for FAM to US$ 220 for LAC1. A decision analysis was carried out in a model including direct and indirect costs and considering retreatment with antibiotics after the first treatment failure and one-year treatment with H2-blockers in case of a second failure. FAM was selected as the most cost-effective option, with an estimated cost of about US$ 300 +/- 148 per patient. However, cost associated to LAC2 was very similar (US$ 320 +/- 58) and the lower standard deviation suggests less variation. Sensitivity analyses, considering reasonable fluctuation in parameters such as eradication rate, cost and follow-up period suggest that a regimen containing a proton pump inhibitor, clarithromycin and amoxycillin may be the most cost-effective treatment. CONCLUSIONS: These results should be confirmed in other settings, specially in ordinary clinical practice, far from clinical research.

The long-term reinfection rate and the course of duodenal ulcer disease after eradication of Helicobacter pylori in a developing country.

OBJECTIVE: The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on the natural history of duodenal ulcer disease and the reinfection rate after treatment in a developing country. METHODS: A total of 111 H. pylori-infected patients with duodenal ulcer were treated with either omeprazole or famotidine plus two antibiotics for 2 wk. Those failed to respond to treatment were retreated with bismuth-based triple therapy. RESULTS: The radication rate was 76% (95% CI: 67-83%). Eventually, H. pylori was eradicated in 96 of the 111 patients (86%), who were followed-up clinically and endoscopically for a mean of 37.2 months. The cumulative reinfection rate after eradication (Kaplan-Meier) was 8%+/-3% in yr 1, 11%+/-4% in yr 2, and 13%+/-4% in yr 3. Nine of the 12 reinfections occurred during yr 1. Recurrence of duodenal ulcer was detected in five patients (5.2%), all of them during yr 1 of follow-up. Histologically, gastritis scores (according to the Sydney system) improved significantly after eradication. CONCLUSIONS: In a high prevalence setting, H. pylori eradication and early reinfection rates after treatment are similar to rates observed in a low prevalence environment, whereas the late reinfection rate seems to be higher. However, up to 3 yr after treatment, most treated patients are free of H. pylori infection and/or ulcer activity. Even longer follow-up studies are necessary to determine whether specific retreatment policies are necessary to maintain long term eradication in developing countries.

[Hepatic veno-occlusive disease associated to the use of azathioprine in a renal transplant recipient]. / Enfermedad venooclusiva hepática asociada a terapia con azatioprina en un paciente trasplantado renal.

We report a 30 years old male, recipient of a kidney allograft and treated with azathioprine, who eighteen days after transplantation had a clinically asymptomatic elevation of total bilirubin and alkaline phosphatases. Nineteen months later, he presented with mild ascites, with a total bilirubin of 3.5 mg/dl, alkaline phosphatases of 308 U/L (normal < 170 U/L) and a prothrombin time at 55% of control. A liver biopsy showed sinusoidal and perivenular fibrosis without inflammation, compatible with chronic venous obstruction. Hepatic veno-occlusive disease is an infrequent complication of azathioprine use.