A Bayesian estimation approach for the mortality in a stage-structured demographic model.

Control interventions in sustainable pest management schemes are set according to the phenology and the population abundance of the pests. This information can be obtained using suitable mathematical models that describe the population dynamics based on individual life history responses to environmental conditions and resource availability. These responses are described by development, fecundity and survival rate functions, which can be estimated from laboratory experiments. If experimental data are not available, data on field population dynamics can be used for their estimation. This is the case of the extrinsic mortality term that appears in the mortality rate function due to biotic factors. We propose a Bayesian approach to estimate the probability density functions of the parameters in the extrinsic mortality rate function, starting from data on population abundance. The method investigates the time variability in the mortality parameters by comparing simulated and observed trajectories. The grape berry moth, a pest of great importance in European vineyards, has been considered as a case study. Simulated data have been considered to evaluate the convergence of the algorithm, while field data have been used to obtain estimates of the mortality for the grape berry moth.

Habitat management of organic vineyard in Northern Italy: the role of cover plants management on arthropod functional biodiversity.

The effect of cover plants on arthropod functional biodiversity was investigated in a vineyard in Northern Italy, through a 3-year field experiment. The following six ground cover plants were tested: Sweet Alyssum; Phacelia; Buckwheat; Faba Bean; Vetch and Oat; control. Arthropods were sampled using different techniques, including collection of leaves, vacuum sampling and sweeping net. Ground cover plant management significantly affected arthropod fauna, including beneficial groups providing ecosystem services like biological control against pests. Many beneficial groups were attracted by ground cover treatments in comparison with control, showing an aggregative numerical response in the plots managed with some of the selected plant species. Alyssum, Buckwheat and 'Vetch and Oat' mixture showed attractiveness on some Hymenoptera parasitoid families, which represented 72.3% of the insects collected by sweeping net and 45.7 by vacuum sampling. Phytoseiidae mites showed a significant increase on leaves of the vineyard plots managed with ground covers, in comparison with control, although they did not show any difference among the treatments. In general, the tested ground cover treatments did not increase dangerous Homoptera populations in comparison with control, with the exception of Alyssum. The potential of ground cover plant management in Italian vineyards is discussed: the overall lack of potential negative effects of the plants tested, combined with an aggregative numerical response for many beneficials, seems to show a potential for their use in Northern Italy vineyards.

Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria.

BACKGROUND: In erythropoietic protoporphyria (EPP), an inherited disease of porphyrin-biosynthesis, the accumulation of protoporphyrin in the skin causes severely painful phototoxic reactions. Symptom prevention was impossible until recently when afamelanotide became available. Afamelanotide-induced skin pigmentation has statistically significantly improved light-tolerance, although the clinical significance of the statistical effect was unknown. OBJECTIVES: To assess clinical effectiveness by recording compliance and safety during prolonged use. METHODS: We report longitudinal observations of 115 ambulatory patients with EPP, who were treated with a total of 1023 afamelanotide implants over a period of up to 8 years at two porphyria centres; one in Rome, Italy, and the other in Zurich, Switzerland. RESULTS: Since the treatment first became available in 2006, the number of patients treated with 16 mg afamelanotide implants rose continuously until June 2014, when 66% of all patients with EPP known to the porphyria centres were treated. Only three patients considered afamelanotide did not meet their expectations for symptom improvement; 23% discontinued the treatment for other, mostly compelling, reasons such as pregnancy or financial restrictions. The quality of life (QoL) scores, measured by an EPP-specific questionnaire, were 31 ± 24% of maximum prior to afamelanotide treatment, rose to 74% after starting afamelanotide and remained at this level during the entire observation period. Only minor adverse events attributable to afamelanotide, predominantly nausea, were recorded. CONCLUSION: Based on the improved QoL scores, high compliance and low discontinuation rates, we conclude that afamelanotide exhibits good clinical effectiveness and good safety in EPP under long-term routine conditions.

Pharmacokinetics of plasma-derived vs. recombinant FVIII concentrates: a comparative study.

Only very few pharmacokinetic (PK) studies comparing plasma derived FVIII (pd-FVIII) against recombinant FVIII (rFVIII) concentrates are available. The studies have been generally conducted to demonstrate the bioequivalence of a new product with an old one. The switch from a plasma-derived FVIII (pd-FVIII) to a rFVIII concentrate is a good moment to enrol the patients in a comparative PK study. To achieve information on the PK characteristics of two different classes of FVIII concentrates, according to two different designs: a 10 FVIII concentration/time point design and a reduced 4-point design. A single dose PK comparing pd- and rFVIII concentrates has been performed in four Haemophilia Centres of Italy. Seventeen haemophilia A patients underwent two subsequent single dose PK studies at the moment of switching. Two-compartment- and Non-compartment-analysis did not show significant differences between the outcomes of PK of pd-FVIII and rFVIII, due to inter-patient variability. In vivo recovery (IVR) of rFVIII was slightly higher than that of pd-FVIII and rFVIII/pd-FVIII AUC ratio was 1.37 in 11/17 patients. The difference is only due to the initial distribution phase because after the first 10 h from the end of the infusion, the two decay curves are overlapping. The elimination half-life of the concentrates was very similar even though a complete bioequivalence was not demonstrated because of a higher AUC of rFVIII concentrates, limited to the distribution phase. The higher Cmax and IVR of rFVIII may be due to the presence of heterodimers activated forms of the recombinant molecules.

Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review.

BACKGROUND: Different rates of inhibitor development after either plasma-derived (pdFVIII) or recombinant (rFVIII) FVIII have been suggested. However, conflicting results are reported in the literature. OBJECTIVES: To systematically review the incidence rates of inhibitor development in previously untreated patients (PUPs) with hemophilia A treated with either pdFVIII or rFVIII and to explore the influence of both study and patient characteristics. METHODS: Summary incidence rates (95% confidence interval) from all included studies for both pdFVIII and rFVIII results were recalculated and pooled. Sensitivity analysis was used to investigate the effect of study design, severity of disease and inhibitor characteristics. Meta-regression and analysis-of-variance were used to investigate the effect of covariates (testing frequency, follow-up duration and intensity of treatment). RESULTS: Two thousand and ninety-four patients (1965 treated with pdFVIII, 887 with rFVIII; median age, 9.6 months) from 24 studies were investigated and 420 patients were observed to develop inhibitors. Pooled incidence rate was 14.3% (10.4-19.4) for pdFVIII and 27.4% (23.6-31.5) for rFVIII; high responding inhibitor incidence rate was 9.3% (6.2-13.7) for pdFVIII and 17.4% (14.2-21.2) for rFVIII. In the multi-way anova study design, study period, testing frequency and median follow-up explained most of the variability, while the source of concentrate lost statistical significance. It was not possible to analyse the effect of intensity of treatment or trigger events such as surgery, and to completely exclude multiple reports of the same patient or changes of concentrate. CONCLUSIONS: These findings underscore the need for randomized controlled trials to address whether or not the risk of inhibitor in PUPs with hemophilia A differs between rFVIII and pdFVIII.

Swiss mice CD1 fed on mussels contaminated by okadaic acid and yessotoxins: effects on thymus and spleen.

The toxicity of okadaic acid (OA) and yessotoxins (YTXs) was studied in mice orally fed on (i) OA (17.80+/-2.41 microg/kg) for 24 h and mouse feed for 24 h; (ii) OA (17.2+/-2.13 microg/kg) plus YTXs (1.30+/-0.12 mg/kg) for 24 h and mouse feed for 24 h; (iii) OA (18.88+/-1.86 microg/kg) plus YTXs (1.45+/-0.12 mg/kg) for 24 h. After toxin treatments the thymus and spleen were examined. More severe morpho-functional modifications were found in the thymus, which presented atrophy, a significant depletion in the lymphoid compartment and angiogenesis. In spite of the impairment, a number of inflammatory cells, reactive to anti-cytokine antibodies, were recruited. Moreover, greater expression of matrix metalloproteinase-9, particularly in cells located near new blood vessels, was observed. Thymus injury was still observed after 48 h. Histopathological changes to the spleen were more evident in mice orally treated for 24 h and immediately sacrificed. The organ showed a significant loss of volume and a fibrous component invaded regions involved in immune functions. In white pulp the marginal zones were reduced, lymphoid nodules contained large germinal centres and the periarteriolar lymphoid sheaths showed cellular depletion. An inflammatory cell response was activated by the recruitment of granulocytes, an increased number of active macrophages and increased immunoreactivity to cytokines. Unlike in the thymus, some evidence of recovery was seen in the spleen. The data suggest that low oral doses of OA alone or OA plus YTXs are able to provoke immunostimulation and systemic immunotoxicity, thus also indicative of tumorigenic properties.

Lethal and sub-lethal yessotoxin dose-induced morpho-functional alterations in intraperitoneal injected Swiss CD1 mice.

Histological and immunocytochemical investigations were performed on different organs (brain, duodenum and thymus) of mice following lethal (420 microg/kg) or sublethal (10 microg/kg) intraperitoneal injection of yessotoxin (YTX). No morpho-functional modifications were observed in large neurons of the cerebral and cerebellar cortex with the sub-lethal dose, nor in the cerebral cortex with the lethal dose. The duodenum also did not show significant alterations. However, there was an inflammation response to the toxin, in which blood cells and cytokines were involved. This was more evident with the lethal YTX dose. The thymus and, in general, the immune system are the main targets of YTX at both the concentrations used. Furthermore, the alterations present in the thymus may support tumorigenic implications.

Corticosterone 21-acetate in vivo induces acute stress in chicken thymus: cell proliferation, apoptosis and cytokine responses.

In vivo effects of acute stress induced by corticosterone 21-acetate in male Gallus domesticus thymus are studied and the steroid actions are evaluated in terms of cell proliferation, apoptosis and cytokine response in 10- and 21-day-old chickens. Steroid treatment induced thymocyte apoptosis and cell death decreased in the cortical-medullar direction and was more evident in younger animals. 24 h after treatment, the observed effect was reversed. The mitotic activity and thymic cells containing cytokine-like molecules were also affected. Indeed, the acute stress stimulated cytokine immunoreactivity to anti-IL-1alpha, IL-6 and TNF-alpha antibodies both in epithelial cells and interdigitating cells located in medullar and cortical-medullar regions. The increased cytokine expression observed after 12 h was maintained after 24 h. The comparison between 10- and 21-day-old chickens showed a lower number of cells containing cytokine-like molecules in younger specimens. The present findings suggest that cytokines activated by acute stress in vivo could contribute to restoring immunological homeostasis and influence thymic glucocorticoid-mediated functions.

Acute toxic effect of the algal yessotoxin on Purkinje cells from the cerebellum of Swiss CD1 mice.

Swiss CD1 mice died less than 2 h after intraperitoneal injection of 420 microg/kg of algal yessotoxin (YTX). The morphological, histochemical and immunocytochemical studies performed on the cerebellar cortex revealed damage to the Purkinje cells. The main cytological alterations were observed in the cytoplasm, while less sufferance was detected in the nucleus. The immunocytochemical experiments showed an increased positivity to S100 protein while there was a decreased response to calbindin D-28K, beta-tubulin and neurofilaments. These changes in intracellular Ca(2+)-binding proteins and the modifications in the cytoskeletal components of Purkinje cells suggest that YTX may be involved in neurological disorders.