Despite recent treatment advances, the majority of patients with chronic hepatitis C fail to respond to antiviral therapy. Although the genetic basis for this resistance is unknown, accumulated evidence suggests that changes in the heterogeneous viral population (quasispecies) may be an important determinant of viral persistence and response to therapy. Sequences within hepatitis C virus (HCV) envelope 1 and envelope 2 genes, inclusive of the hypervariable region 1, were analyzed in parallel with the level of viral replication in serial serum samples obtained from 23 patients who exhibited different patterns of response to therapy and from untreated controls. Our study provides evidence that although the viral diversity before treatment does not predict the response to treatment, the early emergence and dominance of a single viral variant distinguishes patients who will have a sustained therapeutic response from those who subsequently will experience a breakthrough or relapse. A dramatic reduction in genetic diversity leading to an increasingly homogeneous viral population was a consistent feature associated with viral clearance in sustained responders and was independent of HCV genotype. The persistence of variants present before treatment in patients who fail to respond or who experience a breakthrough during therapy strongly suggests the preexistence of viral strains with inherent resistance to IFN. Thus, the study of the evolution of the HCV quasispecies provides prognostic information as early as the first 2 weeks after starting therapy and opens perspectives for elucidating the mechanisms of treatment failure in chronic hepatitis C.
To move a hard table together, humans may coordinate by following the dominant partner’s motion [1–4], but this strategy is unsuitable for a soft mattress where the perceived forces are small. How do partners readily coordinate in such differing interaction dynamics? To address this, we investigated how pairs tracked a target using flexion-extension of their wrists, which were coupled by a hard, medium or soft virtual elastic band. Tracking performance monotonically increased with a stiffer band for the worse partner, who had higher tracking error, at the cost of the skilled partner’s muscular effort. This suggests that the worse partner followed the skilled one’s lead, but simulations show that the results are better explained by a model where partners share movement goals through the forces, whilst the coupling dynamics determine the capacity of communicable information. This model elucidates the versatile mechanism by which humans can coordinate during both hard and soft physical interactions to ensure maximum performance with minimal effort.
Starting from the triangle mesh of a digital shape, that is, mainly an articulated object, we produce a coarse quad layout that can be used in character modeling and animation. Our quad layout follows the intrinsic object structure described by its curve skeleton; it contains few irregular vertices of low degree; it can be immediately refined into a semiregular quad mesh; it provides a structured domain for UV mapping and parametrization. Our method is fast, one-click, and does not require any parameter setting. The user can steer and refine the process through simple interactive tools during the construction of the quad layout
Spike sorting is a typical neural processing technique aimed at identifying the firing activity of individual neurons. It plays a different role in the processing of the signals coming either from a single electrode or an electrode array. In presence of highly noisy recordings, a preliminary denoising stage is required in order to improve the SNR. Despite the significant number of studies in the field, only a few of them deal with peripheral nervous system (PNS) recordings and often the possibility of a real-time implementation is only hinted without any real implementation study. In this paper, a real-time PNS signal processing and classification technique is presented end evaluated on real elec-troneurographic signals taken from the sciatic nerve of rats. A state-of-the-art algorithm, composed of a wavelet denoising preprocessing stage followed by a correlation-based spike sorting and a support vector machine, has been adapted to work on-line in order to improve the processing efficiency while preserving at the most its effectiveness. The algorithm provides some level of adaptiveness with respect to an off-line implementation. On average, the correct classification reach 92.24% with isolated errors that can be easily filtered out. Cycle-accurate profiling results on an off-the-shelf Digital Signal Processor demonstrate the real-time performanc
Aerobic exercise (AE) modulates cortical excitability. It can alter both corticospinal excitability and intra-cortical networks, which has implications for its use as a tool to facilitate processes such as motor learning, where increased levels of excitability are conducive to the induction of neural plasticity. Little is known about how different intensities of AE modulate cortical excitability or how individual-level characteristics impact on it. Therefore, we investigated whether AE intensities, lower than those previously employed, would be effective in increasing cortical excitability. We also examined whether the aerobic fitness of individual participants was related to the magnitude of change in AE-induced cortical excitability. In both experiments we employed transcranial magnetic stimulation to probe corticospinal excitability before and after AE. We show that 20 min of continuous moderate- (40% and 50% of heart rate reserve, HRR), but not low- (30% HRR) intensity AE was effective at increasing corticospinal excitability. We also found that while we observed increased corticospinal excitability following 20 min of continuous moderate-intensity (50% HRR) AE, aerobic fitness was not related to the magnitude of change. Our results suggest that there is a lower bound intensity of AE that is effective at driving changes in cortical excitability, and that while individual-level characteristics are important predictors of response to AE, aerobic fitness is not. Overall these findings have implication for the way that AE is used to facilitate processes such as motor learning, where increased levels of cortical excitability and plasticity are favourable.
Strongyle infections have been traditionally regarded as a possible cause of colic in horses. Aim of the study was the comparison of parasitological status between subjects with or without colic syndrome, with particular attention to small strongyle infections. Coprological analyses were performed on 86 horses: 43 with colic and 43 controls. Strongyle eggs were found in 34/86 horses (prevalence 39.5%), the mean number of strongyles eggs per gram of faeces (EPG) was 145.34 (standard deviation 398.28). All those 34 positive animals had small strongyles infections. Negative binomial multiple regression highlighted no influence of horse sex on strongyle EPG, while there was a negative relationship between age and EPG (p <0.05); the same analysis revealed a significant difference of EPG (p <0.05) between control horses (mean EPG=178.1; standard deviation: 411.4) and horses with surgical colic (mean EPG=68.6 standard deviation: 259.8) when controlling for S. vulgaris presence including it in the model. On the contrary, the intensity of infection in horses with non-surgical colic (mean EPG=154.5; standard deviation: 480.4) did not significantly differed from controls. Similar results were obtained having estimated cyathostomine EPGs as dependent variable. Multinomial logistic regression confirmed the negative relationship between cyathostonine presence and surgical colic occurrence. It is possible that (1) the presence of adult luminal parasites, would have a protective effect against the pathogenic action exerted by the development and emergence of small strongyles larvae from intestinal mucosa; (2) the management practices able to reduce the risk of colics are the same that cause higher exposure to strongyle infective larvae.
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