Integration of animal health and public health surveillance sources to exhaustively inform the risk of zoonosis: An application to echinococcosis in Rio Negro, Argentina.

The analysis of zoonotic disease risk requires the consideration of both human and animal geo-referenced disease incidence data. Here we show an application of joint Bayesian analyses to the study of echinococcosis granulosus (EG) in the province of Rio Negro, Argentina. We focus on merging passive and active surveillance data sources of animal and human EG cases using joint Bayesian spatial and spatio-temporal models. While similar spatial clustering and temporal trending was apparent, there appears to be limited lagged dependence between animal and human outcomes. Beyond the data quality issues relating to missingness at different times, we were able to identify relations between dog and human data and the highest 'at risk' areas for echinococcosis within the province.

A Bayesian unified framework for risk estimation and cluster identification in small area health data analysis.

Many statistical models have been proposed to analyse small area disease data with the aim of describing spatial variation in disease risk. In this paper, we propose a Bayesian hierarchical model that simultaneously allows for risk estimation and cluster identification. Our model formulation assumes that there is an unknown number of risk classes and small areas are assigned to a risk class by means of independent allocation variables. Therefore, areas within each cluster are assumed to share a common risk but they may be geographically separated. The posterior distribution of the parameter representing the number of risk classes is estimated using a novel procedure that combines its prior distribution with an efficient estimate of the marginal likelihood of the data given this parameter. An extension of the model incorporating covariates is also shown. These covariates may incorporate additional information on the problem or they may account for spatial correlation in the data. We illustrate the performance of the proposed model through both a simulation study and a case study of reported cases of varicella in the city of Valencia, Spain.

Biomechanical response of the CNS is associated with frailty in NPH-suspected patients.

Frailty is known to predict dementia. However, its link with neurodegenerative alterations of the central nervous system (CNS) is not well understood at present. We investigated the association between the biomechanical response of the CNS and frailty in older adults suspected of normal pressure hydrocephalus (NPH) presenting with markers of multiple co-existing pathologies. The biomechanical response of the CNS was characterized by the CNS elastance coefficient inferred from phase contrast magnetic resonance imaging and intracranial pressure monitoring during a lumbar infusion test. Frailty was assessed with an index of health deficit accumulation. We found a significant association between the CNS elastance coefficient and frailty, with an effect size comparable to that between frailty and age, the latter being the strongest known risk factor for frailty. Results were independent of CSF dynamics, showing that they are not specific to the NPH neuropathological condition. The CNS biomechanical characterization may help to understand how frailty is related to neurodegeneration and detect the shift from normal to pathological brain ageing.

Integration of animal health and public health surveillance sources to exhaustively inform the risk of zoonosis: An application to visceral leishmaniasis data in Brazil.

Visceral leishmaniasis (VL) is a parasitic disease that is endemic in more than 80 countries, and leads to high fatality rates when left untreated. We investigate the relationship of VL cases in dogs and human cases, specifically for evidence of VL in dogs leading to excess cases in humans. We use surveillance data for dogs and humans for the years 2007-2011 to conduct both spatial and spatio-temporal analyses. Several models are evaluated incorporating varying levels of dependency between dog and human data. Models including dog data show marginal improvement over models without; however, for a subset of spatial units with ample data, models provide concordant risk classification for dogs and humans at high rates (∼70%). Limited reported dog case surveillance data may contribute to the results suggesting little explanatory value in the dog data, as excess human risk was only explained by dog risk in 5% of regions in the spatial analysis.

Gigabar spherical shock generation on the OMEGA laser.

This Letter presents the first experimental demonstration of the capability to launch shocks of several-hundred Mbar in spherical targets--a milestone for shock ignition [R. Betti et al., Phys. Rev. Lett. 98, 155001 (2007)]. Using the temporal delay between the launching of the strong shock at the outer surface of the spherical target and the time when the shock converges at the center, the shock-launching pressure can be inferred using radiation-hydrodynamic simulations. Peak ablation pressures exceeding 300 Mbar are inferred at absorbed laser intensities of ∼3×10(15) W/cm2. The shock strength is shown to be significantly enhanced by the coupling of suprathermal electrons with a total converted energy of up to 8% of the incident laser energy. At the end of the laser pulse, the shock pressure is estimated to exceed ∼1 Gbar because of convergence effects.

Simulation of normal pelvic mobilities in building an MRI-validated biomechanical model.

INTRODUCTION AND HYPOTHESIS: Three-dimensional modeling of feminine pelvic mobility is difficult because the sustaining system is not well understood and ligaments are especially difficult to identify on imaging. METHODS: We built a 3-D numerical model of the pelvic cavity, based on magnetic resonance (MR) images and knowledge about anatomy and validated it systematically. RESULTS: The quantitative results of this model allow for the non-destructive localization of the structures involved in pelvic statics. With a better configuration of the functional pelvis and topological criteria, we can obtain a coherent anatomical and functional model. CONCLUSIONS: This model is the first step in developing a tool to localize and characterize pelvic imbalance in patients.

Ni/Fe-supported over hydrotalcites precursors as catalysts for clean and selective oxidation of Basic Yellow 11: reaction intermediates determination.

In this work, Basic Yellow 11 (BY 11) was employed as model compound to study catalytic wet air oxidation as a pre-treatment step to the conventional biological oxidation. Ni and Fe catalysts supported over hydrotalcite (HT) were prepared by incipient wetness and excess impregnation to obtain catalysts with different metal loadings (from 1 to 10 wt.%). HTs were synthesized by co-precipitation and characterized with XRD, X-ray fluorescence (XRF), BET, thermogravimetric analysis and SEM. Results showed that dye conversion increased with Ni and Fe content up to 7 wt.% and that the most effective catalyst were prepared by incipient wetness impregnation. The influence of metal loading in the catalyst, and the preparation method as well as the reaction conditions was investigated. A mechanism and reaction pathways for BY 11 during catalytic liquid phase oxidation have also been proposed.

Prospective surveillance of multivariate spatial disease data.

Surveillance systems are often focused on more than one disease within a predefined area. On those occasions when outbreaks of disease are likely to be correlated, the use of multivariate surveillance techniques integrating information from multiple diseases allows us to improve the sensitivity and timeliness of outbreak detection. In this article, we present an extension of the surveillance conditional predictive ordinate to monitor multivariate spatial disease data. The proposed surveillance technique, which is defined for each small area and time period as the conditional predictive distribution of those counts of disease higher than expected given the data observed up to the previous time period, alerts us to both small areas of increased disease incidence and the diseases causing the alarm within each area. We investigate its performance within the framework of Bayesian hierarchical Poisson models using a simulation study. An application to diseases of the respiratory system in South Carolina is finally presented.

Catalytic wet air oxidation with Ni- and Fe-doped mixed oxides derived from hydrotalcites.

Catalytic wet air oxidation of Basic Yellow 11 (BY11), a basic dye, was studied in a batch reactor. Layered double hydroxides with the hydrotalcite-like structure containing nickel or iron cations have been prepared by coprecipitation and subsequently calcined leading to Ni- and Fe-doped mixed oxides, respectively. Compared with the results in the wet air oxidation of BY11, these catalysts showed high activity for total organic carbon (TOC), toxicity and dye removal at 120 degrees C and 50 bars after 120 min. It has been demonstrated that the activity depended strongly on the presence of catalyst. The results show that catalysts containing nickel provide a higher extent of oxidation of the dye whereas the reaction carried out with the iron catalyst is faster. The Ni and Fe dispersion determined from the TPR results was higher for the catalysts with a lower Ni or Fe content and decreased for higher Ni or Fe contents. On the basis of activity and selectivity, the Ni containing catalyst with the medium (3%) Ni content was found to be the best catalyst. Finally, a relationship between metal content of the catalyst and reaction rate has been established.

Methyl trypsin loaded poly(D,L-lactide-coglycolide) nanoparticles for contact lens care.

The need of an enzymatic cleaner for soft contact lens care with an improved ocular safety and stability profile led us to evaluate the use of nanoparticles (NPs) of poly(D,L-lactide-coglycolide) (PLGA) and methyl trypsin (MT). NPs were prepared by double emulsion-solvent evaporation technique. A factorial design was performed to select the lactic acid proportion in the copolymer and conditions of the second sonication. The increment in proportion of lactic acid provided higher particle size results. When the time of second sonication was decreased, the entrapment efficiency (EE) increased. PLGA 50:50 NPs were chosen for further development since PLGA 50:50H NPs settled fast with different particle size in the sediment and PLGA 75:25 NPs led to form aggregates. The addition of glycerol to the NPs provided the highest EE of MT (>90%) while the addition of Tetronic 1304 promoted the fast release of enzyme initially and decreased the zeta potential (zeta) up to neutral values after gamma irradiation. NPs are expected to be effective as a lens care cleaner after 3 days or even longer with a very low quantity of enzyme released. Formulations showed an acceptable irritation ocular tolerance after in vitro HET-CAM test and in vivo Draize test.

Possible Parkinson's disease revealed by a pure head resting tremor.

Head tremor is very unusual in Parkinson's disease (PD). Five PD patients presenting a head tremor during the disease evolution have recently been reported. Here we describe a 74 year-old woman with a pure head resting tremor. The tremor was responsive to levodopa and had a 4.7 Hz frequency. A [(123)I]FP-CIT SPECT imaging confirmed a reduction of tracer uptake in the right striatum consistent with PD, that should be confirmed by long-term follow-up.

Purification of an alcohol dehydrogenase involved in the conversion of methional to methionol in Oenococcus oeni IOEB 8406.

Oenococcus oeni, the major lactic acid bacteria involved in malolactic fermentation (MLF) in wine, is able to produce volatile sulfur compounds from methionine. Methional reduction is the last enzymatic step of methionol synthesis in methionine catabolism. Alcohol dehydrogenase (ADH) activity was found to be present in the soluble fraction of O. oeni IOEB 8406. An NAD(P)H-dependent ADH involved in the reduction of methional was then purified to homogeneity. Sequencing of the purified enzyme and amino acid sequence comparison with the database revealed the presence of a conserved sequence motif specific to the medium-chain zinc-containing NAD(P)H-dependent ADHs. Despite the great importance of ADH activities in wine flavor modification, this is the first report of the purification of an ADH isolated from O. oeni. The purified ADH does not seem to be involved in the modification of buttery and lactic notes or to be involved in the specific formation of volatile alcohols during MLF. The enzyme was not strictly specific of methional reduction and the highest reducing activity was obtained with acetaldehyde as substrate. The function of the purified ADH remains unclear, although the role of the sulfur atom in methional molecules in the interaction between enzyme and substrate was evidenced.

Pathways that produce volatile sulphur compounds from methionine in Oenococcus oeni.

AIMS: Determination of pathways involved in synthesis of volatile sulphur compounds (VSC) from methionine by Oenococcus oeni isolated from wine. METHODS AND RESULTS: Production of VSC by O. oeni from methionine was investigated during bacterial cultures and in assays performed in the presence of resting cells or protein fractions. Cells of O. oeni grown in a medium supplemented with methionine produced methanethiol, dimethyl disulphide, methionol and 3-(methylthio)propionic acid. Methional was also detected, but only transiently during the exponential growth phase. It was converted to methionol and 3-(methylthio) propionic acid in assays. Although this acid could be produced alternatively from 2-oxo-4-(methylthio) butyric acid (KMBA) by oxidative decarboxylation. In addition, KMBA was a precursor for methanethiol and dimethyl disulphide synthesis. Interestingly, assays with resting cells and protein fractions suggested that a specific enzyme could be involved in this conversion in O. oeni. CONCLUSION: This work shows that methional and KMBA are the key intermediates for VSC synthesis from methionine in O. oeni. Putative enzymatic and chemical pathways responsible for the production of these VSC are discussed. SIGNIFICANCE AND IMPACT OF THE STUDY: This work confirms the capacity of O. oeni to metabolize methionine and describes the involvement of potential enzymatic pathways.

Recombinant protein Bd37 protected gerbils against heterologous challenges with isolates of Babesia divergens polymorphic for the bd37 gene.

The Bd37gene encoding for a glycosyl-phosphatidyl-inositol anchored protein of Babesia divergens displays genetic polymorphisms among isolates. Five major polymorphic groups (clades) were shown by PCR-RFLP among different B. divergens isolates. Each group has been characterized according to a reference Bd37 gene (Rouen87, W8843, Y5, 6303E and 1705B). Recombinant (GST fusion) protein (Bd37r) expressed from the Bd37 gene, was used as antigen in a saponin-based formulation and was able to protect gerbils, after 2 injections at low dose vaccine concentration (1 mug per dose), against a virulent challenge with the B. divergens Rouen87 isolate. In spite of polymorphism of Bd37 gene, Bd37r induced complete immunoprotection against challenges with each of the 5 reference isolate groups defined by PCR-RFLP.

[Heat stroke and fulminans hepatitis: is MARS system relevant?]. / Coup de chaleur d'exercice avec hépatite fulminante: intérêt du système MARS?

Exertional heat stroke (EHS) is a life-threatening condition caused by an extreme elevation in core body temperature. Acute liver failure has been reported during EHS justifying liver transplantation in some cases. The Molecular Adsorbent Recirculating System (MARS) could be indicated in such situations. We report a case of a 58-year old patient who suffered acute liver failure occurring after EHS. The patient was referred for liver transplantation and benefited of MARS therapy. After three sessions of MARS, liver function improved progressively and the transplantation was not necessary. The patient completely recovered.

Changes to hepatocyte ploidy and binuclearity profiles during human chronic viral hepatitis.

BACKGROUND AND AIMS: The importance of the hepatocyte ploidisation pattern to the control of cell proliferation and differentiation has been well established. However, there are no data that have characterised hepatocyte ploidy at various stages of chronic liver inflammation and fibrosis in vivo. METHODS: We therefore investigated hepatocyte ploidy/binuclearity patterns in 57 patients with chronic hepatitis, using a recently developed methodology which allows simultaneous hepatocyte ploidy and binuclearity analyses on the same liver section. RESULTS: The percentage of mononuclear diploid hepatocytes was significantly reduced in patients with high hepatitis activity and marked fibrosis (low activity: 75.1 (18.8)% v high activity: 61.8 (21.6)%, p=0.0111, and low fibrosis: 77.3 (13.8)% v high fibrosis: 57.4 (23.3)%, p=0.0002). Accordingly, the percentage of mononuclear polyploid hepatocytes increased in patients with high hepatitis activity and marked fibrosis (low activity: 11.9 (15.5)% v high activity: 22.2 (20.1)%, p=0.0166, and low fibrosis: 9.4 (10.7)% v high fibrosis: 26.4 (21.6)%, p=0.0001). In addition, the fraction of binuclear hepatocytes was significantly higher in patients with hepatitis B virus (HBV) than in those with hepatitis C virus (HCV) infections (HBV: 18.2 (7.6)% v HCV: 12.0 (4.8)%; p=0.0020). Under multivariate analysis, HBV infection was an independent factor accounting for the larger binuclear hepatocyte fraction (p=0.0294). CONCLUSION: Our results revealed an increase in the polyploid hepatocyte fraction which correlates with the severity of chronic hepatitis; moreover, we demonstrated that HBV and HCV related chronic hepatitis exhibited distinctive hepatocyte ploidy patterns, thus allowing the suggestion that these two viral infections may modulate liver ploidy through different mechanisms.

Association between sequence polymorphism in an epitope of Babesia divergens Bd37 exoantigen and protection induced by passive transfer.

In Europe, Babesia divergens is the major agent responsible for babesiosis in cattle and can occasionally infect splenectomised humans. Recently, we reported the characterisation of a 37 kDa exoantigen (Bd37) anchored in the merozoite membrane of B. divergens by a glycosylphosphatidyl-inositol. After phospholipase hydrolyse of the glycosylphosphatidyl-inositol anchor, the Bd37 antigen could be isolated in the plasma of the infected host and from the in vitro culture supernatants. Immunisation of mice with a gel-filtration protective fraction of B. divergens exoantigens, produced a monoclonal antibody (MAb), called F4.2F8-INT, directed against Bd37. In the present study, we report data on passive protection using MAb F4.2F8-INT. This MAb was able to completely protect against virulent challenges with B. divergens isolates Rouen 1987 (Rouen87) and Weybridge 8843 (W8843) but had no protective effect against another French isolate from Massif Central (6303E). Physical characterisation of the epitope recognised by F4.2F8-INT allowed us to explain the differences observed between these isolates by western blotting and passive protection. These results suggest that the antigen carrying this epitope could be used as a target in the development of a recombinant vaccine against B. divergens babesiosis.

Babesia divergens: cloning and biochemical characterization of Bd37.

The immunoprotective potential of Babesia divergens antigens released in supernatants of in vitro cultures of the parasite is generally known. Among a number of parasite molecules, a 37 kDa protein has been found in the supernatants of Babesia divergens cultures. In this report the cloning and biochemical characterization of this protein, called Bd37, are described. In addition, the processing of the protein was studied in vitro. Results suggest that Bd37 is encoded by a single copy gene. Bd37 appears to be a merozoite-associated molecule attached to the surface by a glycosylphosphatidylinositol moiety containing a palmitate residue attached to the inositol ring. In addition, it is demonstrated that both extremities of the protein are linked by a disulphide bond. Results further indicate that a soluble, hydrophilic form of Bd37 can be released from the merozoite surface by GPI-specific phospholipase D. The potential role the Bd37 protein and the GPI anchor are discussed.

[Procalcitonin in the early diagnosis of invasive bacterial infection in febrile infants]. / Procalcitonina para el diagnóstico precoz de infección bacteriana invasiva en el lactante febril.

BACKGROUND: Procalcitonin (PCT) it is a new marker of bacterial infection. Because of its shorter half-life and earlier ascent it offers advantages over C-reactive protein (CRP). OBJECTIVE: To compare the diagnostic performance of PCT in the early detection of invasive bacterial infection in infants with that of CPR. MATERIAL AND METHODS: Between January of 1998 and February of 2000 we performed a prospective observational study in the emergency department of infants aged between 1 and 36 months who had been treated for fever and for whom PCT and CRP plasmatic values had been obtained. Plasmatic PCT and PCR values were evaluated and correlated with the final diagnosis. ROC curves for both markers were calculated. RESULTS: One hundred infants with a mean age of 8.8 months (SD 7.59) were included in four groups of 25 patients each (viral infection, localized bacterial infection, invasive bacterial infection and control group). The mean PCT and CRP values in invasive bacterial infections [PCT: 14.45 ng/mL (SD 27.95) and CRP: 95.10 mg/L (SD 7 2.77)] were significantly higher than in non-invasive infections [PCT: 0.27 ng/mL (SD 0.19) and CRP: 25.67 mg/L (SD 33.04)] but the diagnostic performance of PCT was better. The area under the curve for PCT was 0.95 (SD 0.03), which was significantly higher (p < 0.001) than that obtained for CRP [0.81 (SD 0.05)]. The optimal cut-off for PCT was > 0.4 ng/mL (sensitivity: 95.5 %; specificity: 86.4 %) and that for CRP was > 42.9 mg/L (sensitivity: 75 %; specificity: 81.8 %). In infants who had fever for less than 12 hours (n 30) the area under the curve for PCT was 0.90 (SD 0.06), which was higher (p < 0.001) than that for PCR [0.64 (SD 0.11)]. The optimal cut-off for PCT in this group was > 0.4 ng/mL (sensitivity: 90 %; specificity: 94 %) and that for CRP was > 26.6 mg/L (sensitivity: 60 %; specificity: 77.8 %). CONCLUSIONS: The diagnostic performance of PCT was higher than that of CRP in the early detection of invasive infection in febrile infants, even when evolution was less than 12 hours.