Harmonised monitoring of antimicrobial resistance in Salmonella and Campylobacter isolates from food animals in the European Union

Many Member States of the European Union (EU) currently monitor antimicrobial resistance in zoonotic agents, including Salmonella and Campylobacter. According to Directive 2003/99/EC, Member States shall ensure that the monitoring provides comparable data on the occurrence of antimicrobial resistance. The European Commission asked the European Food Safety Authority to prepare detailed specifications for harmonised schemes for monitoring antimicrobial resistance. The objective of these specifications is to lay down provisions for a monitoring and reporting scheme for Salmonella in fowl (Gallus gallus), turkeys and pigs, and for Campylobacter jejuni and Campylobacter coli in broiler chickens. The current specifications are considered to be a first step towards a gradual implementation of comprehensive antimicrobial resistance monitoring at the EU level. These specifications propose to test a common set of antimicrobial agents against available cut-off values and a specified concentration range to determine the susceptibility of Salmonella and Campylobacter. Using isolates collected through programmes in which the sampling frame covers all epidemiological units of the national production, the target number of Salmonella isolates to be included in the antimicrobial resistance monitoring per Member State per year is 170 for each study population (i.e., laying hens, broilers, turkeys and slaughter pigs). The target number of Campylobacter isolates to be included in the antimicrobial resistance monitoring per Member State per year is 170 for each study population (i.e., broilers). The results of the antimicrobial resistance monitoring are assessed and reported in the yearly national report on trends and sources of zoonoses, zoonotic agents and antimicrobial resistance.

Risk Assessment of the Introduction of Porcine Reproductive and Respiratory Syndrome Virus via Boar Semen into Switzerland as an Example of a PRRSV-Free Country

Switzerland is currently porcine reproductive and respiratory syndrome virus (PRRSV) free, but semen imports from PRRSV-infected European countries are increasing. As the virus can be transmitted via semen, for example, when a free boar stud becomes infected, and the risk of its import in terms of PRRSV introduction is unknown, the annual probability to accidentally import the virus into Switzerland was estimated in a risk assessment. A quantitative stochastic model was set up with data comprised by import figures of 2010, interviews with boar stud owners and expert opinion. It resulted in an annual median number of 0.18 imported ejaculates (= imported semen doses from one collection from one donor) from PRRSV-infected boars. Hence, one infected ejaculate would be imported every 6 years and infect a mean of 10 sows. These results suggest that under current circumstances, there is a substantial risk of PRRSV introduction into Switzerland via imported boar semen and that measures to enhance safety of imports should be taken. The time from infection of a previously negative boar stud to its detection had the highest impact on the number of imported 'positive' ejaculates. Therefore, emphasis should be placed on PRRSV monitoring protocols in boar studs. Results indicated that a substantial increase in safety could only be achieved with much tighter sampling protocols than currently performed. Generally, the model could easily be customized for other applications like other countries or regions or even sow farms that want to estimate their risk when purchasing semen from a particular boar stud.

Optical pen-size reflectometer for monitoring of early dental erosion in native and polished enamels

Application of the specular reflection intensity was previously reported for the quantification of early dental erosion. Further development of the technique and assembly of the miniaturized pen-size instrument are described. The optical system was adjusted to fit into a handy device which could potentially access different positions in the oral cavity. The assembled instrument could successfully detect early erosion progression in both polished (n=70) and native (n=20) human enamels. Different severities of enamel erosion were induced by varying incubation time of polished enamel in 1% citric acid (pH=3.60, 0.5 to 10 min), while the native incisors were treated in the commercial orange juice (Tropicana Pure Premium®, pH=3.85, 10 to 60 min). The instrument provided a good differentiation between various severities of the erosion in vitro. The size of the measurement spot affected the erosion monitoring in native enamel (human incisors). The erosion measurement in the 0.7-mm (diameter) cervical spots showed systematically lower reflection intensities compared with the analysis of central and incisal small spots. The application of larger spot areas (2.3 mm) for the erosion monitoring revealed no effect (p>0.05) of the spot position on the reflection signal. High variation of the teeth susceptibility toward in vitro erosion was detected in native enamel.

ANOVA kernels and RKHS of zero mean functions for model-based sensitivity analysis

Given a reproducing kernel Hilbert space (H,〈.,.〉)(H,〈.,.〉) of real-valued functions and a suitable measure μμ over the source space D⊂RD⊂R, we decompose HH as the sum of a subspace of centered functions for μμ and its orthogonal in HH. This decomposition leads to a special case of ANOVA kernels, for which the functional ANOVA representation of the best predictor can be elegantly derived, either in an interpolation or regularization framework. The proposed kernels appear to be particularly convenient for analyzing the effect of each (group of) variable(s) and computing sensitivity indices without recursivity.

Actigraphic monitoring of physical activity in clinical trials in schizophrenia

Schizophrenia is still associated with poor outcome, which is mainly related to negative symptoms, reduced physical activity and low quality of life. Physical activity can be objectively measured without distress using wrist actigraphy. The activity levels during the wake periods of the day have been informative on psychopathology and antipsychotic medication. Several studies demonstrated prominent negative symptoms to be associated with reduced activity levels with strongest correlations in chronic patients. Particularly, the avolition score is correlated with reduced activity levels. Moreover, activity levels differ between DSM-IV schizophrenia spectrum disorders and subtypes as well as between patients treated with olanzapine or risperidone. The longitudinal course of activity levels during an psychotic episode demonstrates considerable variance between subjects. During a psychotic episode patients with low activity levels at baseline experience an amelioration of negative symptoms. In contrast, patients with high activity levels at baseline have stable low negative syndrome scores. Between psychotic episodes less variance is observed. Actigraphy is easily applied in schizophrenia and allows collecting large amounts of crosssectional or longitudinal data. With larger numbers of subjects in controlled trials, continuous recording of activity would foster the detection of different outcome trajectories, which may prove as useful groups to target interventions. In clinical trials, activity monitoring may supplement and validate measures of the negative syndrome and its avolition factor or serve as an outcome marker for physical activity, which is important for metabolic issues and quality of life.

Living Renal Allograft Transplantation: Diffusion-weighted MR Imaging in Longitudinal Follow-up of the Donated and the Remaining Kidney.

Purpose To determine whether diffusion-weighted (DW) magnetic resonance (MR) imaging in living renal allograft donation allows monitoring of potential changes in the nontransplanted remaining kidney of the donor because of unilateral nephrectomy and changes in the transplanted kidney before and after transplantation in donor and recipient, respectively, and whether DW MR parameters are correlated in the same kidney before and after transplantation. Materials and Methods The study protocol was approved by the local ethics committee; written informed consent was obtained. Thirteen healthy kidney donors and their corresponding recipients prospectively underwent DW MR imaging (multiple b values) in donors before donation and in donors and recipients at day 8 and months 3 and 12 after donation. Total apparent diffusion coefficient (ADCT) values were determined; contribution of microcirculation was quantified in perfusion fraction (FP). Longitudinal changes of diffusion parameters were compared (repeated-measures one-way analysis of variance with post hoc pairwise comparisons). Correlations were tested (linear regression). Results ADCT values in nontransplanted kidney of donors increased from a preexplantation value of (188 ± 9 [standard deviation]) to (202 ± 11) × 10(-5) mm(2)/sec in medulla and from (199 ± 11) to (210 ± 13) × 10(-5) mm(2)/sec in cortex 1 week after donation (P < .004). Medullary, but not cortical, ADCT values stayed increased up to 1 year. ADCT values in allografts in recipients were stable. Compared with values obtained before transplantation in donors, the corticomedullary difference was reduced in allografts (P < .03). Cortical ADCT values correlated with estimated glomerular filtration rate in recipients (R = 0.56, P < .001) but not donors. Cortical ADCT values in the same kidney before transplantation in donors correlated with those in recipients on day 8 after transplantation (R = 0.77, P = .006). FP did not show significant changes. Conclusion DW MR imaging depicts early adaptations in the remaining nontransplanted kidney of donors after nephrectomy. All diffusion parameters remained constant in allograft recipients after transplantation. This method has potential monitoring utility, although assessment of clinical relevance is needed. © RSNA, 2013 Online supplemental material is available for this article.

Estimating the mean and standard deviation of concentration distributions using censored samples

Environmental data sets of pollutant concentrations in air, water, and soil frequently include unquantified sample values reported only as being below the analytical method detection limit. These values, referred to as censored values, should be considered in the estimation of distribution parameters as each represents some value of pollutant concentration between zero and the detection limit. Most of the currently accepted methods for estimating the population parameters of environmental data sets containing censored values rely upon the assumption of an underlying normal (or transformed normal) distribution. This assumption can result in unacceptable levels of error in parameter estimation due to the unbounded left tail of the normal distribution. With the beta distribution, which is bounded by the same range of a distribution of concentrations, $\rm\lbrack0\le x\le1\rbrack,$ parameter estimation errors resulting from improper distribution bounds are avoided. This work developed a method that uses the beta distribution to estimate population parameters from censored environmental data sets and evaluated its performance in comparison to currently accepted methods that rely upon an underlying normal (or transformed normal) distribution. Data sets were generated assuming typical values encountered in environmental pollutant evaluation for mean, standard deviation, and number of variates. For each set of model values, data sets were generated assuming that the data was distributed either normally, lognormally, or according to a beta distribution. For varying levels of censoring, two established methods of parameter estimation, regression on normal ordered statistics, and regression on lognormal ordered statistics, were used to estimate the known mean and standard deviation of each data set. The method developed for this study, employing a beta distribution assumption, was also used to estimate parameters and the relative accuracy of all three methods were compared. For data sets of all three distribution types, and for censoring levels up to 50%, the performance of the new method equaled, if not exceeded, the performance of the two established methods. Because of its robustness in parameter estimation regardless of distribution type or censoring level, the method employing the beta distribution should be considered for full development in estimating parameters for censored environmental data sets. ^

In Situ Monitoring of Free-Phase Gas Accumulation and Release in Peatlands Using Ground Penetrating Radar (GPR)

We tested a set of surface common mid-point (CMP) ground penetrating radar (GPR) surveys combined with elevation rods ( to monitor surface deformation) and gas flux measurements to investigate in-situ biogenic gas dynamics and ebullition events in a northern peatland ( raised bog). The main findings are: ( 1) changes in the two-way travel time from the surface to prominent reflectors allow estimation of average gas contents and evolution of free-phase gas (FPG); ( 2) peat surface deformation and gas flux measurements are strongly consistent with GPR estimated changes in FPG content over time; ( 3) rapid decreases in atmospheric pressure are associated with increased gas flux; and ( 4) single ebullition events can induce releases of methane much larger ( up to 192 g/m(2)) than fluxes reported by others. These results indicate that GPR is a useful tool for assessing the spatial distribution, temporal variation, and volume of biogenic gas deposits in peatlands.

Seasonal Deuterium Excess in a Tien Shan Ice Core: Influence of Moisture Transport and Recycling in Central Asia

Stable water isotope (delta(18)O, deltaD) data from a high elevation (5100 masl) ice core recovered from the Tien Shan Mountains, Kyrgyzstan, display a seasonal cycle in deuterium excess (d = deltaD - 8* delta(18)O) related to changes in the regional hydrologic cycle during 1994 - 2000. While there is a strong correlation (r(2) = 0.98) between delta(18)O and dD in the ice core samples, the regression slope (6.9) and mean d value (23.0) are significantly different than the global meteoric water line values. The resulting time-series ice core d profile contains distinct winter maxima and summer minima, with a yearly d amplitude of similar to 15 - 20parts per thousand. Local-scale processes that may affect d values preserved in the ice core are not consistent with the observed seasonal variability. Data from Central Asian monitoring sites in the Global Network of Isotopes in Precipitation (GNIP) have similar seasonal d changes. We suggest that regional-scale hydrological conditions, including seasonal changes in moisture source, transport, and recycling in the Caspian/ Aral Sea region, are responsible for the observed spatial and temporal d variability.

Seasonal Geophysical Monitoring of Biogenic Gases in a Northern Peatland: Implications for Temporal and Spatial Variability in Free Phase Gas Production Rates

A set of high resolution surface ground penetrating radar (GPR) surveys, combined with elevation rod ( to monitor surface deformation) and gas flux measurements, were used to investigate in situ biogenic gas dynamics within a northern peatland (Caribou Bog, Maine). Gas production rates were directly estimated from the time series of GPR measurements. Spatial variability in gas production was also investigated by comparing two sites with different geological and ecological attributes, showing differences and/or similarities depending on season. One site characterized by thick highly humified peat deposits (5-6 m), wooded heath vegetation and open pools showed large ebullition events during the summer season, with estimated emissions (based on an assumed range of CH(4) concentration) between 100 and 172 g CH(4) m(-2) during a single event. The other site characterized by thinner less humified peat deposits (2-3 m) and shrub vegetation showed much smaller ebullition events during the same season (between 13 and 23 g CH(4) m(-2)). A consistent period of free-phase gas (FPG) accumulation during the fall and winter, enhanced by the frozen surficial peat acting as a confining layer, was followed by a decrease in FPG after the snow/ice melt that released estimated fluxes between 100 and 200 g CH(4) m(-2) from both sites. Estimated FPG production rates during periods of biogenic gas accumulation ranged between 0.22 and 2.00 g CH(4) m(3) d(-1) and reflected strong seasonal and spatial variability associated with differences in temperature, peat soil properties, and/or depositional attributes (e. g., stratigraphy). Periods of decreased atmospheric pressure coincided with short-period increases in biogenic gas flux, including a very rapid decrease in FPG content associated with an ebullition event that released an estimated 39 and 67 g CH(4) m(-2) in less than 3.5 hours. These results provide insights into the spatial and seasonal variability in production and emission of biogenic gases from northern peatlands.

Ordinal patterns in epileptic brains: Analysis of intracranial EEG and simultaneous EEG-fMRI

Epileptic seizures are associated with high behavioral stereotypy of the patients. In the EEG of epilepsy patients characteristic signal patterns can be found during and between seizures. Here we use ordinal patterns to analyze EEGs of epilepsy patients and quantify the degree of signal determinism. Besides relative signal redundancy and the fraction of forbidden patterns we introduce the fraction of under-represented patterns as a new measure. Using the logistic map, parameter scans are performed to explore the sensitivity of the measures to signal determinism. Thereafter, application is made to two types of EEGs recorded in two epilepsy patients. Intracranial EEG shows pronounced determinism peaks during seizures. Finally, we demonstrate that ordinal patterns may be useful for improving analysis of non-invasive simultaneous EEG-fMRI.

Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy.

PURPOSE Therapeutic drug monitoring of patients receiving once daily aminoglycoside therapy can be performed using pharmacokinetic (PK) formulas or Bayesian calculations. While these methods produced comparable results, their performance has never been checked against full PK profiles. We performed a PK study in order to compare both methods and to determine the best time-points to estimate AUC0-24 and peak concentrations (C max). METHODS We obtained full PK profiles in 14 patients receiving a once daily aminoglycoside therapy. PK parameters were calculated with PKSolver using non-compartmental methods. The calculated PK parameters were then compared with parameters estimated using an algorithm based on two serum concentrations (two-point method) or the software TCIWorks (Bayesian method). RESULTS For tobramycin and gentamicin, AUC0-24 and C max could be reliably estimated using a first serum concentration obtained at 1 h and a second one between 8 and 10 h after start of the infusion. The two-point and the Bayesian method produced similar results. For amikacin, AUC0-24 could reliably be estimated by both methods. C max was underestimated by 10-20% by the two-point method and by up to 30% with a large variation by the Bayesian method. CONCLUSIONS The ideal time-points for therapeutic drug monitoring of once daily administered aminoglycosides are 1 h after start of a 30-min infusion for the first time-point and 8-10 h after start of the infusion for the second time-point. Duration of the infusion and accurate registration of the time-points of blood drawing are essential for obtaining precise predictions.

The effects of cardiac output and pulmonary arterial hypertension on volumetric capnography derived-variables during normoxia and hypoxia

The aim of this study was to test the effect of cardiac output (CO) and pulmonary artery hypertension (PHT) on volumetric capnography (VCap) derived-variables. Nine pigs were mechanically ventilated using fixed ventilatory settings. Two steps of PHT were induced by IV infusion of a thromboxane analogue: PHT25 [mean pulmonary arterial pressure (MPAP) of 25 mmHg] and PHT40 (MPAP of 40 mmHg). CO was increased by 50 % from baseline (COup) with an infusion of dobutamine ≥5 μg kg(-1) min(-1) and decreased by 40 % from baseline (COdown) infusing sodium nitroglycerine ≥30 μg kg(-1) min(-1) plus esmolol 500 μg kg(-1) min(-1). Another state of PHT and COdown was induced by severe hypoxemia (FiO2 0.07). Invasive hemodynamic data and VCap were recorded and compared before and after each step using a mixed random effects model. Compared to baseline, the normalized slope of phase III (SnIII) increased by 32 % in PHT25 and by 22 % in PHT40. SnIII decreased non-significantly by 4 % with COdown. A combination of PHT and COdown associated with severe hypoxemia increased SnIII by 28 % compared to baseline. The elimination of CO2 per breath decreased by 7 % in PHT40 and by 12 % in COdown but increased only slightly with COup. Dead space variables did not change significantly along the protocol. At constant ventilation and body metabolism, pulmonary artery hypertension and decreases in CO had the biggest effects on the SnIII of the volumetric capnogram and on the elimination of CO2.