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

On the Structure of Diregular Digraphs With Defect 1

The Moore bound for a diregular digraph of degree d and diameter k is M d;k = 1 + d + : : : + d k . It is known that digraphs of order M d;k do not exist for d ? 1 and k ? 1. In this paper we study digraphs of order M d;k \Gamma 1, that is, digraphs with defect 1, denoted by (d; k)-digraphs. If G is a (d; k)-digraph, then for each vertex v of G there exists a vertex w (called the repeat of v) such that there are two walks of lengths k from v to w. In the case of w = v we call v a selfrepeat. To study the existence of (d; k)-digraphs, we may divide the digraphs into two classes according to whether or not they contain a selfrepeat vertex. For d 3 and k 3 we prove that (d; k)-digraphs contain either no selfrepeats or exactly k selfrepeats. Furthermore, we show that every (d; k)-digraph with k selfrepeats must contain a cycle of length k as well as possibly another (d 1 ; k)-digraph as its subdigraph (where d 1 ! d). For diameter 2 we give further conditions for the existence of (d;..

Nailed connection behavior in light-frame wood shear walls with an intermediate layer of insulation

The shear strength and stiffness of light-frame wood shear walls is highly dependent on the behavior of their individual nailed connections. Eighty-four nailed connection specimens were tested under shear loading to determine the effect of including rigid insulation as an intermediate material between the sheathing and framing elements in a light-frame wood shear wall. Each specimen contained common 10d or 16d nails, 15.9 mm oriented strandboard sheathing, spruce-pine-fir lumber, and rigid insulation in varied thicknesses between 0 and 38.1 mm. From the load-deformation results, maximum load, yield load, and stiffness were assessed using curve-fitting and yield-point determination methods. The results indicate that, as the insulation thickness increases, the connection strength and stiffness both exhibit a steep reduction. In addition, nonlinear two-dimensional (2D) finite-element models of the same nailed connections were developed. These models showed good correlation with experimental data and served to confirm that the decline in strength and stiffness observed in the tests is due to the introduction of the insulation

Testing and analytical modelling of intermediate gypsum wallboard in wood shear wall sheathing to framing connections

Light frame wood shear walls resist lateral loads primarily through the individual nailed connections between the sheathing and framing. The most common arrangement for such shear walls is to have sheathing on one side and gypsum board on the other. In various situations it can be desirable to increase the capacity of this type of walls by fastening a layer of sheathing overtop of the drywall. This study considered the effect that an intermediate layer of gypsum has on the strength of nailed connections in shear walls, while maintaining code-defined minimum nail penetrations. Results show that intermediate gypsum placed between the sheathing and framing resulted in significantly reduced capacity and stiffness. Analytical modelling showed good correlation with experimental results. The implications of the experimental testing and modelling are that code provisions allowing the use of intermediate gypsum wallboard should not be relied upon