Fish as Reservoirs and Vectors of Vibrio cholerae

Vibrio cholerae, the etiologic agent of cholera, is autochthonous to various aquatic environments, but despite intensive efforts its ecology remains an enigma. Recently, it was suggested that copepods and chironomids, both considered as natural reservoirs of V. cholerae, are dispersed by migratory waterbirds, thus possibly distributing the bacteria between water bodies within and between continents. Although fish have been implicated in the scientific literature with cholera cases, as far as we know, no study actually surveyed the presence of the bacteria in the fish. Here we show for the first time that fish of various species and habitats contain V. cholerae in their digestive tract. Fish (n = 110) were randomly sampled from freshwater and marine habitats in Israel. Ten different fish species sampled from freshwater habitats (lake, rivers and fish ponds), and one marine species, were found to carry V. cholerae. The fish intestine of Sarotherodon galilaeus harboured ca. 5×103 V. cholerae cfu per 1 gr intestine content—high rates compared with known V. cholerae cfu numbers in the bacteria's natural reservoirs. Our results, combined with evidence from the literature, suggest that fish are reservoirs of V. cholerae. As fish carrying the bacteria swim from one location to another (some fish species move from rivers to lakes or sea and vice versa), they serve as vectors on a small scale. Nevertheless, fish are consumed by waterbirds, which disseminate the bacteria on a global scale. Moreover, V. cholerae isolates had the ability to degrade chitin, indicating a commensal relationship between V. cholerae and fish. Better understanding of V. cholerae ecology can help reduce the times that human beings come into contact with this pathogen and thus minimize the health risk this poses

The multi-stripe travelling salesman problem

In the classical Travelling Salesman Problem (TSP), the objective function sums the costs for travelling from one city to the next city along the tour. In the q-stripe TSP with q ≥ 1, the objective function sums the costs for travelling from one city to each of the next q cities along the tour. The resulting q-stripe TSP generalizes the TSP and forms a special case of the quadratic assignment problem. We analyze the computational complexity of the q-stripe TSP for various classes of specially structured distance matrices. We derive NP-hardness results as well as polyomially solvable cases. One of our main results generalizes a well-known theorem of Kalmanson from the classical TSP to the q-stripe TSP

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

A new single-loop method for steady-state analysis and design of networks with switching power converters

A common strategy for steady-state analysis of switching power converters has been to pose the analysis problem as a nonlinear boundary-value problem which can be solved using time-domain shooting methods. However, the resulting nonlinear equations for closed loop converters are, in general, ill-conditioned. The proposed method uses a new set of constraints which define the nonlinear boundary-value problem. This new mapping results in substantial convergence improvement and, in addition, it allows for computation of converter steady-state in a single Newton's iteration loop. The problems of convergence failures due to the initial guess referred in the past are explained. The proposed method has been verified using several hard and soft-switching closed-loop converters

A complex ripple analysis of switching DC/DC power converter circuits

An efficient and simple algorithm for comprehensive ripple analysis of switching power converter circuits is presented. Ripple analysis includes investigation of rms and peak-to-peak ripples as well as analysis of the ripple harmonic spectra of voltage and current waveforms. Knowledge of voltage and current ripples either inside the power train circuit or those present in the power converter input and output filter circuits has crucial practical implications. Ignoring the harmonic contents can lead to inaccurate results in determining the power conversion efficiency. A shortcoming of currently used methods for power conversion efficiency calculation is demonstrated. Computation results for hard and soft switching closed-loop power converter circuits are included