Effect of immune pressure on hepatitis C virus evolution: insights from a single-source outbreak

The host's immune response to hepatitis C virus (HCV) can result in the selection of characteristic mutations (adaptations) that enable the virus to escape this response. The ability of the virus to mutate at these sites is dependent on the incoming virus, the fitness cost incurred by the mutation, and the benefit to the virus in escaping the response. Studies examining viral adaptation in chronic HCV infection have shown that these characteristic immune escape mutations can be observed at the population level as human leukocyte antigen (HLA)-specific viral polymorphisms. We examined 63 individuals with chronic HCV infection who were infected from a single HCV genotype 1b source. Our aim was to determine the extent to which the host's immune pressure affects HCV diversity and the ways in which the sequence of the incoming virus, including preexisting escape mutations, can influence subsequent mutations in recipients and infection outcomes. Conclusion: HCV sequences from these individuals revealed 29 significant associations between specific HLA types within the new hosts and variations within their viruses, which likely represent new viral adaptations. These associations did not overlap with previously reported adaptations for genotypes 1a and 3a and possibly reflected a combination of constraint due to the incoming virus and genetic distance between the strains. However, these sites accounted for only a portion of the sites in which viral diversity was observed in the new hosts. Furthermore, preexisting viral adaptations in the incoming (source) virus likely influenced the outcomes in the new hosts.

Angiographic C-arm CT- versus MDCT-guided stereotactic punctures of liver lesions: nonrigid phantom study

OBJECTIVE Angiographic C-arm CT may allow performing percutaneous stereotactic tumor ablations in the interventional radiology suite. Our purpose was to evaluate the accuracy of using C-arm CT for single and multimodality image fusions and to compare the targeting accuracy of liver lesions with the reference standard of MDCT. MATERIALS AND METHODS C-arm CT and MDCT scans were obtained of a nonrigid rapid prototyping liver phantom containing five 1-mm targets that were placed under skin-simulating deformable plastic foam. Target registration errors of image fusion were evaluated for single-modality and multimodality image fusions. A navigation system and stereotactic aiming device were used to evaluate target positioning errors on postinterventional scans with the needles in place fused with the C-arm CT or MDCT planning images. RESULTS Target registration error of the image fusion showed no significant difference (p > 0.05) between both modalities. In five series with a total of 25 punctures for each modality, the lateral target positioning error (i.e., the lateral distance between the needle tip and the planned trajectory) was similar for C-arm CT (mean [± SD], 1.6 ± 0.6 mm) and MDCT (1.82 ± .97 mm) (p = 0.33). CONCLUSION In a nonrigid liver phantom, angiographic C-arm CT may provide similar image fusion accuracy for comparison of intra- and postprocedure control images with the planning images and enables stereotactic targeting accuracy similar to that of MDCT.

Long-distance photogrammetric trait estimation in free-ranging animals: A new approach

The acquisition of accurate information on the size of traits in animals is fundamental for the study of animal ecology and evolution and their management. We demonstrate how morphological traits of free-ranging animals can reliably be estimated on very large observation distances of several hundred meters by the use of ordinary digital photographic equipment and simple photogrammetric software. In our study, we estimated the length of horn annuli in free-ranging male Alpine ibex (Capra ibex) by taking already measured horn annuli of conspecifics on the same photographs as scaling units. Comparisons with hand-measured horn annuli lengths and repeatability analyses revealed a high accuracy of the photogrammetric estimates. If length estimations of specific horn annuli are based on multiple photographs measurement errors of <5.5 mm can be expected. In the current study the application of the described photogrammetric procedure increased the sample size of animals with known horn annuli length by an additional 104%. The presented photogrammetric procedure is of broad applicability and represents an easy, robust and cost-efficient method for the measuring of individuals in populations where animals are hard to capture or to approach.

Long Distance Electron Transfer at the Metal/Alkanethiol/Ionic Liquid Interface

The rate constants of simple electron transfer (ET) reactions in room temperature ionic liquids (ILs) available now are rather high, typically at the edge of experimental accuracy. To consider ET phenomena in these media in view of theory developed earlier for molecular solvents, it is crucial to provide quantitative comparison of experimental kinetic data for certain reactions. We report this comparison for ferrocene/ferrocenium reaction. The ET distance is fixed by Au surface modification by alkanethiol self-assembled monolayers, which were characterized by in situ scanning tunneling microscopy. The dependence of ln kapp on barrier thickness in the range of ca. 6–20 Å is linear, with a slope typical for the same plots in aqueous media. This result confirms diabatic mode of Fc oxidation at long distance. The data for shorter ET distances point to the adiabatic regime of ET at a bare gold surface, although more detailed computational studies are required to justify this conclusion.

Detection of muscle wasting in patients with chronic heart failure using C-terminal agrin fragment: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

AIMS Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting. We sought to investigate the diagnostic properties of CAF in muscle wasting among patients with heart failure. METHODS AND RESULTS We assessed serum CAF levels in 196 patients who participated in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Muscle wasting was identified using dual-energy X-ray absorptiometry (DEXA) in 38 patients (19.4%). Patients with muscle wasting demonstrated higher CAF values than those without (125.1 ± 59.5 pmol/L vs. 103.8 ± 42.9 pmol/L, P = 0.01). Using receiver operating characteristics (ROC), we calculated the optimal CAF value to identify patients with muscle wasting as >87.5 pmol/L, which had a sensitivity of 78.9% and a specificity of 43.7%. The area under the ROC curve was 0.63 (95% confidence interval 0.56-0.70). Using simple regression, we found that serum CAF was associated with handgrip (R = - 0.17, P = 0.03) and quadriceps strength (R = - 0.31, P < 0.0001), peak oxygen consumption (R = - 0.5, P < 0.0001), 6-min walk distance (R = - 0.32, P < 0.0001), and gait speed (R = - 0.2, P = 0.001), as well as with parameters of kidney and liver function, iron metabolism and storage. CONCLUSION CAF shows good sensitivity for the detection of skeletal muscle wasting in patients with heart failure. Its assessment may be useful to identify patients who should undergo additional testing, such as detailed body composition analysis. As no other biomarker is currently available, further investigation is warranted.

The utility of preoperative six-minute-walk distance in lung transplantation

RATIONALE The use of 6-minute-walk distance (6MWD) as an indicator of exercise capacity to predict postoperative survival in lung transplantation has not previously been well studied. OBJECTIVES To evaluate the association between 6MWD and postoperative survival following lung transplantation. METHODS Adult, first time, lung-only transplantations per the United Network for Organ Sharing database from May 2005 to December 2011 were analyzed. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine the association between preoperative 6MWD and post-transplant survival after adjusting for potential confounders. A receiver operating characteristic curve was used to determine the 6MWD value that provided maximal separation in 1-year mortality. A subanalysis was performed to assess the association between 6MWD and post-transplant survival by disease category. MEASUREMENTS AND MAIN RESULTS A total of 9,526 patients were included for analysis. The median 6MWD was 787 ft (25th-75th percentiles = 450-1,082 ft). Increasing 6MWD was associated with significantly lower overall hazard of death (P < 0.001). Continuous increase in walk distance through 1,200-1,400 ft conferred an incremental survival advantage. Although 6MWD strongly correlated with survival, the impact of a single dichotomous value to predict outcomes was limited. All disease categories demonstrated significantly longer survival with increasing 6MWD (P ≤ 0.009) except pulmonary vascular disease (P = 0.74); however, the low volume in this category (n = 312; 3.3%) may limit the ability to detect an association. CONCLUSIONS 6MWD is significantly associated with post-transplant survival and is best incorporated into transplant evaluations on a continuous basis given limited ability of a single, dichotomous value to predict outcomes.

The dust environment of comet 67P/Churyumov-Gerasimenko from Rosetta OSIRIS and VLT observations in the 4.5 to 2.9 AU heliocentric distance range inbound

Context. The ESA Rosetta spacecraft, currently orbiting around cornet 67P/Churyumov-Gerasimenko, has already provided in situ measurements of the dust grain properties from several instruments, particularly OSIRIS and GIADA. We propose adding value to those measurements by combining them with ground-based observations of the dust tail to monitor the overall, time-dependent dust-production rate and size distribution. Aims. To constrain the dust grain properties, we take Rosetta OSIRIS and GIADA results into account, and combine OSIRIS data during the approach phase (from late April to early June 2014) with a large data set of ground-based images that were acquired with the ESO Very Large Telescope (VLT) from February to November 2014. Methods. A Monte Carlo dust tail code, which has already been used to characterise the dust environments of several comets and active asteroids, has been applied to retrieve the dust parameters. Key properties of the grains (density, velocity, and size distribution) were obtained from. Rosetta observations: these parameters were used as input of the code to considerably reduce the number of free parameters. In this way, the overall dust mass-loss rate and its dependence on the heliocentric distance could be obtained accurately. Results. The dust parameters derived from the inner coma measurements by OSIRIS and GIADA and from distant imaging using VLT data are consistent, except for the power index of the size-distribution function, which is alpha = -3, instead of alpha = -2, for grains smaller than 1 mm. This is possibly linked to the presence of fluffy aggregates in the coma. The onset of cometary activity occurs at approximately 4.3 AU, with a dust production rate of 0.5 kg/s, increasing up to 15 kg/s at 2.9 AU. This implies a dust-to-gas mass ratio varying between 3.8 and 6.5 for the best-fit model when combined with water-production rates from the MIRO experiment.

Using multiple landscape genetic approaches to test the validity of genetic clusters in a species characterized by an isolation-by-distance pattern

Bayesian clustering methods are typically used to identify barriers to gene flow, but they are prone to deduce artificial subdivisions in a study population characterized by an isolation-by-distance pattern (IbD). Here we analysed the landscape genetic structure of a population of wild boars (Sus scrofa) from south-western Germany. Two clustering methods inferred the presence of the same genetic discontinuity. However, the population in question was characterized by a strong IbD pattern. While landscape-resistance modelling failed to identify landscape features that influenced wild boar movement, partial Mantel tests and multiple regression of distance matrices (MRDMs) suggested that the empirically inferred clusters were separated by a genuine barrier. When simulating random lines bisecting the study area, 60% of the unique barriers represented, according to partial Mantel tests and MRDMs, significant obstacles to gene flow. By contrast, the random-lines simulation showed that the boundaries of the inferred empirical clusters corresponded to the most important genetic discontinuity in the study area. Given the degree of habitat fragmentation separating the two empirical partitions, it is likely that the clustering programs correctly identified a barrier to gene flow. The differing results between the work published here and other studies suggest that it will be very difficult to draw general conclusions about habitat permeability in wild boar from individual studies.