Paper 4: EUROCAT statistical monitoring: identification and investigation of ten year trends of congenital anomalies in Europe.

BACKGROUND: As part of EUROCAT's surveillance of congenital anomalies in Europe, a statistical monitoring system has been developed to detect recent clusters or long-term (10 year) time trends. The purpose of this article is to describe the system for the identification and investigation of 10-year time trends, conceived as a "screening" tool ultimately leading to the identification of trends which may be due to changing teratogenic factors.METHODS: The EUROCAT database consists of all cases of congenital anomalies including livebirths, fetal deaths from 20 weeks gestational age, and terminations of pregnancy for fetal anomaly. Monitoring of 10-year trends is performed for each registry for each of 96 non-independent EUROCAT congenital anomaly subgroups, while Pan-Europe analysis combines data from all registries. The monitoring results are reviewed, prioritized according to a prioritization strategy, and communicated to registries for investigation. Twenty-one registries covering over 4 million births, from 1999 to 2008, were included in monitoring in 2010.CONCLUSIONS: Significant increasing trends were detected for abdominal wall anomalies, gastroschisis, hypospadias, Trisomy 18 and renal dysplasia in the Pan-Europe analysis while 68 increasing trends were identified in individual registries. A decreasing trend was detected in over one-third of anomaly subgroups in the Pan-Europe analysis, and 16.9% of individual registry tests. Registry preliminary investigations indicated that many trends are due to changes in data quality, ascertainment, screening, or diagnostic methods. Some trends are inevitably chance phenomena related to multiple testing, while others seem to represent real and continuing change needing further investigation and response by regional/national public health authorities.

The Visual Dysphagia Questionnaire: Evaluating the first Tool for Assessing Food Consistency-Dependent Dysphagia in Eosinophilic Esophagitis

Background and Aims: The international EEsAI study group iscurrently developing the first a ctivity index specific forEosinophilic Esophagitis (EoE). None of the existing dysphagiaquestionnaires take into account the consistency of theingested food t hat considerably impacts the symptompresentation. Goal: To d evelop and evaluate an E oE-specificquestionnaire assessing dysphagia caused by foods of differentconsistencies.Methods: B ased on patient interviews and chart reviews, a nexpert panel ( EEsAI study g roup) identified internationallystandardizedfood prototypes t ypically a ssociated with EoErelateddysphagia. Food consistencies were c orrelated withEoE-related d ysphagia, t aking into account p otential f oodavoidance and f ood processing. This V isual D ysphagiaQuestionnaire (VDQ) was piloted in 20 patients and is currentlyevaluated in a cohort of 150 adult EoE patients.Results: T he following 8 food c onsistency prototypes w ereidentified: soft foods (pudding, jelly), grits, toast bread, Frenchfries, dry rice, ground meat, raw fibrous f oods (eg. apple,carrot), s olid m eat. Dysphagia was r anked o n a 4-point Likertscale (0=no difficulties; 3= severe difficulties, food will not pass).First analysis demonstrated that severity of dysphagia is relatedto the eosinophil load and presence of esophageal strictures.Conclusions: T he VDQ i s the first EoE-specific tool f orassessing dysphagia caused by i nternationally-standardizedfoods of different consistencies. This instrument also addressesfood avoidance behaviour and food processing habits. This toolperformed well in a p ilot study a nd is currently evaluated in acohort of 150 adult EoE patients.

Development of a control banding tool for nanomaterials

Control banding (CB) can be a useful tool for managing the potential risks of nanomaterials. The here proposed CB, which should be part of an overall risk control strategy, groups materials by hazard and emission potential. The resulting decision matrix proposes control bands adapted to the risk potential levels and helps define an action plan. If this plan is not practical and financially feasible, a full risk assessment is launched. The hazard banding combines key concepts of nanomaterial toxicology: translocation across biological barriers, fibrous nature, solubility, and reactivity. Already existing classifications specific to the nanomaterial can be used "as is." Otherwise, the toxicity of bulk or analogous substances gives an initial hazard band, which is increased if the substance is not easily soluble or if it has a higher reactivity than the substance. The emission potential bands are defined by the nanomaterials' physical form and process characteristics. Quantities, frequencies, and existing control measures are taken into account during the definition of the action plan. Control strategies range from room ventilation to full containment with expert advice. This CB approach, once validated, can be easily embedded in risk management systems. It allows integrating new toxicity data and needs no exposure data. [Authors]

AssociationViewer: a scalable and integrated software tool for visualization of large-scale variation data in genomic context.

SUMMARY: We present a tool designed for visualization of large-scale genetic and genomic data exemplified by results from genome-wide association studies. This software provides an integrated framework to facilitate the interpretation of SNP association studies in genomic context. Gene annotations can be retrieved from Ensembl, linkage disequilibrium data downloaded from HapMap and custom data imported in BED or WIG format. AssociationViewer integrates functionalities that enable the aggregation or intersection of data tracks. It implements an efficient cache system and allows the display of several, very large-scale genomic datasets. AVAILABILITY: The Java code for AssociationViewer is distributed under the GNU General Public Licence and has been tested on Microsoft Windows XP, MacOSX and GNU/Linux operating systems. It is available from the SourceForge repository. This also includes Java webstart, documentation and example datafiles.

Numerical simulation of ambient seismic wavefield modification caused by pore-fluid effects in an oil reservoir

We have modeled numerically the seismic response of a poroelastic inclusion with properties applicable to an oil reservoir that interacts with an ambient wavefield. The model includes wave-induced fluid flow caused by pressure differences between mesoscopic-scale (i.e., in the order of centimeters to meters) heterogeneities. We used a viscoelastic approximation on the macroscopic scale to implement the attenuation and dispersion resulting from this mesoscopic-scale theory in numerical simulations of wave propagation on the kilometer scale. This upscaling method includes finite-element modeling of wave-induced fluid flow to determine effective seismic properties of the poroelastic media, such as attenuation of P- and S-waves. The fitted, equivalent, viscoelastic behavior is implemented in finite-difference wave propagation simulations. With this two-stage process, we model numerically the quasi-poroelastic wave-propagation on the kilometer scale and study the impact of fluid properties and fluid saturation on the modeled seismic amplitudes. In particular, we addressed the question of whether poroelastic effects within an oil reservoir may be a plausible explanation for low-frequency ambient wavefield modifications observed at oil fields in recent years. Our results indicate that ambient wavefield modification is expected to occur for oil reservoirs exhibiting high attenuation. Whether or not such modifications can be detected in surface recordings, however, will depend on acquisition design and noise mitigation processing as well as site-specific conditions, such as the geologic complexity of the subsurface, the nature of the ambient wavefield, and the amount of surface noise.

A numerical characterization of hypersurface singularities

In this note we give a numerical characterization of hypersurface singularities in terms of the normalized Hilbert-Samuel coefficients, and we interpret this result from the point of view of rigid polynomials.

A numerical model for the gamma-ray emission of the microquasar LS 5039

The possible association between the microquasar LS 5039 and the EGRET source 3EG J1824-1514 suggests that microquasars could also be sources of high energy gamma-rays. In this paper, we explore, with a detailed numerical model, if this system can produce the emission detected by EGRET (>100 MeV) through inverse Compton (IC) scattering. Our numerical approach considers a population of relativistic electrons entrained in a cylindrical inhomogeneous jet, interacting with both the radiation and the magnetic fields, taking into account the Thomson and Klein-Nishina regimes of interaction. The computed spectrum reproduces the observed spectral characteristics at very high energy.

A fully adaptive numerical approximation for a two-dimensional epidemic model with nonlinear cross-diffusion

An epidemic model is formulated by a reactionâeuro"diffusion system where the spatial pattern formation is driven by cross-diffusion. The reaction terms describe the local dynamics of susceptible and infected species, whereas the diffusion terms account for the spatial distribution dynamics. For both self-diffusion and cross-diffusion, nonlinear constitutive assumptions are suggested. To simulate the pattern formation two finite volume formulations are proposed, which employ a conservative and a non-conservative discretization, respectively. An efficient simulation is obtained by a fully adaptive multiresolution strategy. Numerical examples illustrate the impact of the cross-diffusion on the pattern formation.

Regenerating cortical connections in a dish: the entorhino-hippocampal organotypic slice co-culture as tool for pharmacological screening of molecules promoting axon regeneration

We present a method for using long-term organotypic slice co-cultures of the entorhino-hippocampal formation to analyze the axon-regenerative properties of a determined compound. The culture method is based on the membrane interphase method, which is easy to perform and is generally reproducible. The degree of axonal regeneration after treatment in lesioned cultures can be seen directly using green fluorescent protein (GFP) transgenic mice or by axon tracing and histological methods. Possible changes in cell morphology after pharmacological treatment can be determined easily by focal in vitro electroporation. The well-preserved cytoarchitectonics in the co-culture facilitate the analysis of identified cells or regenerating axons. The protocol takes up to a month.

On some numerical aspects of an active strain model in cardiac mechanics

We are interested in the development, implementation and testing of an orthotropic model for cardiac contraction based on an active strain decomposition. Our model addresses the coupling of a transversely isotropic mechanical description at the cell level, with an orthotropic constitutive law for incompressible tissue at the macroscopic level. The main differences with the active stress model are addressed in detail, and a finite element discretization using Taylor-Hood and MINI elements is proposed and illustrated with numerical examples.

Numerical analysis of wave-induced fluid flow effects on seismic data: Application to monitoring of CO2 storage at the Sleipner Field

In this work we analyze how patchy distributions of CO2 and brine within sand reservoirs may lead to significant attenuation and velocity dispersion effects, which in turn may have a profound impact on surface seismic data. The ultimate goal of this paper is to contribute to the understanding of these processes within the framework of the seismic monitoring of CO2 sequestration, a key strategy to mitigate global warming. We first carry out a Monte Carlo analysis to study the statistical behavior of attenuation and velocity dispersion of compressional waves traveling through rocks with properties similar to those at the Utsira Sand, Sleipner field, containing quasi-fractal patchy distributions of CO2 and brine. These results show that the mean patch size and CO2 saturation play key roles in the observed wave-induced fluid flow effects. The latter can be remarkably important when CO2 concentrations are low and mean patch sizes are relatively large. To analyze these effects on the corresponding surface seismic data, we perform numerical simulations of wave propagation considering reservoir models and CO2 accumulation patterns similar to the CO2 injection site in the Sleipner field. These numerical experiments suggest that wave-induced fluid flow effects may produce changes in the reservoir's seismic response, modifying significantly the main seismic attributes usually employed in the characterization of these environments. Consequently, the determination of the nature of the fluid distributions as well as the proper modeling of the seismic data constitute important aspects that should not be ignored in the seismic monitoring of CO2 sequestration problems.

Evaluation of a clinical tool for early etiology identification in status epilepticus.

OBJECTIVES: Because early etiologic identification is critical to select appropriate specific status epilepticus (SE) management, we aim to validate a clinical tool we developed that uses history and readily available investigations to guide prompt etiologic assessment. METHODS: This prospective multicenter study included all adult patients treated for SE of all but anoxic causes from four academic centers. The proposed tool is designed as a checklist covering frequent precipitating factors for SE. The study team completed the checklist at the time the patient was identified by electroencephalography (EEG) request. Only information available in the emergency department or at the time of in-hospital SE identification was used. Concordance between the etiology indicated by the tool and the determined etiology at hospital discharge was analyzed, together with interrater agreement. RESULTS: Two hundred twelve patients were included. Concordance between the etiology hypothesis generated using the tool and the finally determined etiology was 88.7% (95% confidence interval (CI) 86.4-89.8) (κ = 0.88). Interrater agreement was 83.3% (95% CI 80.4-96) (κ = 0.81). SIGNIFICANCE: This tool is valid and reliable for identification early the etiology of an SE. Physicians managing patients in SE may benefit from using it to identify promptly the underlying etiology, thus facilitating selection of the appropriate treatment.

Numerical analysis of the impact of charcoal production on soil hydrological behavior, runoff response and erosion susceptibility

The impact of charcoal production on soil hydraulic properties, runoff response and erosion susceptibility were studied in both field and simulation experiments. Core and composite samples, from 12 randomly selected sites within the catchment of Kotokosu were taken from the 0-10 cm layer of a charcoal site soil (CSS) and adjacent field soils (AFS). These samples were used to determine saturated hydraulic conductivity (Ksat), bulk density, total porosity, soil texture and color. Infiltration, surface albedo and soil surface temperature were also measured in both CSS and AFS. Measured properties were used as entries in a rainfall runoff simulation experiment on a smooth (5 % slope) plot of 25 x 25 m grids with 10 cm resolutions. Typical rainfall intensities of the study watershed (high, moderate and low) were applied to five different combinations of Ks distributions that could be expected in this landscape. The results showed significantly (p < 0.01) higher flow characteristics of the soil under charcoal kilns (increase of 88 %). Infiltration was enhanced and runoff volume reduced significantly. The results showed runoff reduction of about 37 and 18 %, and runoff coefficient ranging from 0.47-0.75 and 0.04-0.39 or simulation based on high (200 mm h-1) and moderate (100 mm h-1) rainfall events over the CSS and AFS areas, respectively. Other potential impacts of charcoal production on watershed hydrology were described. The results presented, together with watershed measurements, when available, are expected to enhance understanding of the hydrological responses of ecosystems to indiscriminate charcoal production and related activities in this region.