Intra- and interlaboratory reliability of a cryopreserved trout hepatocyte assay for the prediction of chemical bioaccumulation potential

Measured rates of intrinsic clearance determined using cryopreserved trout hepatocytes can be extrapolated to the whole animal as a means of improving modeled bioaccumulation predictions for fish. To date, however, the intra- and interlaboratory reliability of this procedure has not been determined. In the present study, three laboratories determined in vitro intrinsic clearance of six reference compounds (benzo[a]pyrene, 4-nonylphenol, di-tert-butyl phenol, fenthion, methoxychlor and o-terphenyl) by conducting substrate depletion experiments with cryopreserved trout hepatocytes from a single source. O-terphenyl was excluded from the final analysis due to nonfirst-order depletion kinetics and significant loss from denatured controls. For the other five compounds, intralaboratory variability (% CV) in measured in vitro intrinsic clearance values ranged from 4.1 to 30%, while interlaboratory variability ranged from 27 to 61%. Predicted bioconcentration factors based on in vitro clearance values exhibited a reduced level of interlaboratory variability (5.3-38% CV). The results of this study demonstrate that cryopreserved trout hepatocytes can be used to reliably obtain in vitro intrinsic clearance of xenobiotics, which provides support for the application of this in vitro method in a weight-of-evidence approach to chemical bioaccumulation assessment.

Effect of surface restoring on subsurface variability in a climate model during 1949–2005

Initializing the ocean for decadal predictability studies is a challenge, as it requires reconstructing the little observed subsurface trajectory of ocean variability. In this study we explore to what extent surface nudging using well-observed sea surface temperature (SST) can reconstruct the deeper ocean variations for the 1949–2005 period. An ensemble made with a nudged version of the IPSLCM5A model and compared to ocean reanalyses and reconstructed datasets. The SST is restored to observations using a physically-based relaxation coefficient, in contrast to earlier studies, which use a much larger value. The assessment is restricted to the regions where the ocean reanalyses agree, i.e. in the upper 500 m of the ocean, although this can be latitude and basin dependent. Significant reconstruction of the subsurface is achieved in specific regions, namely region of subduction in the subtropical Atlantic, below the thermocline in the equatorial Pacific and, in some cases, in the North Atlantic deep convection regions. Beyond the mean correlations, ocean integrals are used to explore the time evolution of the correlation over 20-year windows. Classical fixed depth heat content diagnostics do not exhibit any significant reconstruction between the different existing bservation-based references and can therefore not be used to assess global average time-varying correlations in the nudged simulations. Using the physically based average temperature above an isotherm (14°C) alleviates this issue in the tropics and subtropics and shows significant reconstruction of these quantities in the nudged simulations for several decades. This skill is attributed to the wind stress reconstruction in the tropics, as already demonstrated in a perfect model study using the same model. Thus, we also show here the robustness of this result in an historical and observational context.

The Neuropsychological Assessment of Cognitive Deficits Considering Measures of Performance Variability

Neuropsychologists often face interpretational difficulties when assessing cognitive deficits, particularly in cases of unclear cerebral etiology. How can we be sure whether a single test score below the population average is indicative of a pathological brain condition or normal? In the past few years, the topic of intra-individual performance variability has gained great interest. On the basis of a large normative sample, two measures of performance variability and their importance for neuropsychological interpretation will be presented in this paper: the number of low scores and the level of dispersion.We conclude that low scores are common in healthy individuals. On the other hand, the level of dispersion is relatively small. Here, base rate information about abnormally low scores and abnormally high dispersion across cognitive abilities are providedto improve the awareness of normal variability and to serve clinicians as additional interpretive measures in the diagnostic process.

Spatial variability and potential impacts of climate change on flood and debris flow hazard zone mapping and implications for risk management

The main goals of this study were to identifythe alpine torrent catchments that are sensitive to climatic changes and to assess the robustness of the methods for the elaboration of flood and debris flow hazard zone maps to specific effects of climate changes. In this study, a procedure for the identification and localization of torrent catchments in which the climate scenarios will modify the hazard situation was developed. In two case studies, the impacts of a potential increase of precipitation intensities to the delimited hazard zones were studied. The identification and localization of the torrent and river catchments, where unfavourable changes in the hazard situation occur, could eliminate speculative and unnecessary measures against the impacts of climate changes like a general enlargement of hazard zones or a general over dimensioning of protection structures for the whole territory. The results showed a high spatial variability of the sensitivity of catchments to climate changes. In sensitive catchments, the sediment management in alpine torrents will meet future challenges due to a higher rate for sediment removal from retention basins. The case studies showed a remarkable increase of the areas affected by floods and debris flow when considering possible future precipitation intensities in hazard mapping. But, the calculated increase in extent of future hazard zones lay within the uncertainty of the methods used today for the delimitation of the hazard zones. Thus, the consideration of the uncertainties laying in the methods for the elaboration of hazard zone maps in the torrent and river catchments sensitive to climate changes would provide a useful instrument for the consideration of potential future climate conditions. The study demonstrated that weak points in protection structures in future will become more important in risk management activities.

Good reproducibility of heart rate variability after orthostatic challenge in patients with a history of acute coronary syndrome

BACKGROUND: Several parameters of heart rate variability (HRV) have been shown to predict the risk of sudden cardiac death (SCD) in cardiac patients. There is consensus that risk prediction is increased when measuring HRV during specific provocations such as orthostatic challenge. For the first time, we provide data on reproducibility of such a test in patients with a history of acute coronary syndrome. METHODS: Sixty male patients (65+/-8years) with a history of acute coronary syndrome on stable medication were included. HRV was measured in supine (5min) and standing (5min) position on 2 occasions separated by two weeks. For risk assessment relevant time-domain [standard deviation of all R-R intervals (SDNN) and root mean squared standard differences between adjacent R-R intervals (RMSSD)], frequency domain [low-frequency power (LF), high-frequency power (HF) and LF/HF power ratio] and short-term fractal scaling component (DF1) were computed. Absolute reproducibility was assessed with the standard errors of the mean (SEM) and 95% limits of random variation, and relative reproducibility by the intraclass correlation coefficient (ICC). RESULTS: We found comparable SEMs and ICCs in supine position and after an orthostatic challenge test. All ICCs were good to excellent (ICCs between 0.636 and 0.869). CONCLUSIONS: Reproducibility of HRV parameters during orthostatic challenge is good and comparable with supine position.

Quantitative multi-slice computed tomography assessment of the mitral valvular complex for transcatheter mitral valve interventions part 1: systematic measurement methodology and inter-observer variability

AIMS Transcatheter mitral valve replacement (TMVR) is an emerging technology with the potential to treat patients with severe mitral regurgitation at excessive risk for surgical mitral valve surgery. Multimodal imaging of the mitral valvular complex and surrounding structures will be an important component for patient selection for TMVR. Our aim was to describe and evaluate a systematic multi-slice computed tomography (MSCT) image analysis methodology that provides measurements relevant for transcatheter mitral valve replacement. METHODS AND RESULTS A systematic step-by-step measurement methodology is described for structures of the mitral valvular complex including: the mitral valve annulus, left ventricle, left atrium, papillary muscles and left ventricular outflow tract. To evaluate reproducibility, two observers applied this methodology to a retrospective series of 49 cardiac MSCT scans in patients with heart failure and significant mitral regurgitation. For each of 25 geometrical metrics, we evaluated inter-observer difference and intra-class correlation. The inter-observer difference was below 10% and the intra-class correlation was above 0.81 for measurements of critical importance in the sizing of TMVR devices: the mitral valve annulus diameters, area, perimeter, the inter-trigone distance, and the aorto-mitral angle. CONCLUSIONS MSCT can provide measurements that are important for patient selection and sizing of TMVR devices. These measurements have excellent inter-observer reproducibility in patients with functional mitral regurgitation.

Genetic variability and limited clonality of Mycoplasma hyorhinis in pig herds

Mycoplasma hyorhinis is a common inhabitant of the upper respiratory tract and tonsils of pigs. Its role as a possible pathogen remains controversial. In order to gain more insight into the epidemiology and population structure of M. hyorhinis we genetically characterized 60 isolates by multi locus sequence typing (MLST). The M. hyorhinis strains originated from Swiss and German pig herds with knowledge on the clinical background. The MLST scheme of Tocqueville et al. (J. Clin. Microbiol. 2014) was optimized, primers for the six MLST gene fragments were newly designed to allow amplification and sequencing with a single protocol. A total of 27 ST were observed with the 60 strains, 26 of those were previously unknown types. Generally identical genotypes were observed within a farm but they differed between farms. The identical genotype was also observed in three different Swiss farms. On the other Hand different genotypes within a farm were found with three German farms. The Swiss isolates formed a distinct cluster but otherwise there was no geographical nor a clinical association with specific Clusters observed. Data shows a high variability of M. hyorhinis comparable to what is observed for Mycoplasma hyopneumoniae. Similar to this pathogen the population structure of M. hyorhinis also shows some limited clonality with predominant genotypes within an animal and a single farm but different ones between farms. The comparable population structure of M. hyopneumoniae and M. hyorhinis could indicate a similar evolution of the two species in the common pig host.