A Multinational Analysis of Mutations and Heterogeneity in PZase, RpsA, and PanD Associated with Pyrazinamide Resistance in M/XDR Mycobacterium tuberculosis.

Pyrazinamide (PZA) is an important first-line drug in all existing and new tuberculosis (TB) treatment regimens. PZA-resistance in M. tuberculosis is increasing, especially among M/XDR cases. Noted issues with PZA Drug Susceptibility Testing (DST) have driven the search for alternative tests. This study provides a comprehensive assessment of PZA molecular diagnostics in M/XDR TB cases. A set of 296, mostly XDR, clinical M. tuberculosis isolates from four countries were subjected to DST for eight drugs, confirmatory Wayne's assay, and whole-genome sequencing. Three genes implicated in PZA resistance, pncA, rpsA, and panD were investigated. Assuming all non-synonymous mutations cause resistance, we report 90% sensitivity and 65% specificity for a pncA-based molecular test. The addition of rpsA and panD potentially provides 2% increase in sensitivity. Molecular heterogeneity in pncA was associated with resistance and should be evaluated as a diagnostic tool. Mutations near the N-terminus and C-terminus of PZase were associated with East-Asian and Euro-American lineages, respectively. Finally, Euro-American isolates are most likely to have a wild-type PZase and escape molecular detection. Overall, the 8-10% resistance without markers may point to alternative mechanisms of resistance. Confirmatory mutagenesis may improve the disconcertingly low specificity but reduce sensitivity since not all mutations may cause resistance

Bosonic reaction-diffusion processes on scale-free networks

Reaction-diffusion processes can be adopted to model a large number of dynamics on complex networks, such as transport processes or epidemic outbreaks. In most cases, however, they have been studied from a fermionic perspective, in which each vertex can be occupied by at most one particle. While still useful, this approach suffers from some drawbacks, the most important probably being the difficulty to implement reactions involving more than two particles simultaneously. Here we introduce a general framework for the study of bosonic reaction-diffusion processes on complex networks, in which there is no restriction on the number of interacting particles that a vertex can host. We describe these processes theoretically by means of continuous time heterogeneous mean-field theory and divide them into two main classes: steady state and monotonously decaying processes. We analyze specific examples of both behaviors within the class of one-species process, comparing the results (whenever possible) with the corresponding fermionic counterparts. We find that the time evolution and critical properties of the particle density are independent of the fermionic or bosonic nature of the process, while differences exist in the functional form of the density of occupied vertices in a given degree class k. We implement a continuous time Monte Carlo algorithm, well suited for general bosonic simulations, which allow us to confirm the analytical predictions formulated within mean-field theory. Our results, both at the theoretical and numerical level, can be easily generalized to tackle more complex, multi-species, reaction-diffusion processes, and open a promising path for a general study and classification of this kind of dynamical systems on complex networks.Comment: 15 pages, 7 figure

Variability of the HeI5876 A line in early type chemically peculiar stars

Chemically peculiar stars present spectral and photometric variability with a single period. In the oblique rotator model, the non homogeneous distribution of elements on the stellar surface is at the origin of the observed variations. As to helium weak stars, it has been suggested that photometric and helium line equivalent width variations are out of phase. To understand the behaviour of helium in CP stars, we have obtained time resolved spectra of the HeI5876 A line for a sample of 16 chemically peculiar stars in the spectral range B3 -- A1 and belonging to different sub-groups. The HeI5876 A line is too weak to be measured in the spectra of the stars HD 24155, HD 41269, and HD 220825. No variation of the equivalent width of the selected He line has been revealed in the stars HD 22920, HD 24587, HD 36589, HD 49606, and HD 209515. The equivalent width variation of the HeI5876 A line is in phase with the photometric variability for the stars HD 43819, HD 171247 and HD 176582. On the contrary it is out of phase for the stars HD 28843, HD 182255 and HD 223640. No clear relation has been found for the stars HD 26571 and HD 177003.Comment: 8 pages, 9 figures. 1998, A&AS in pres