Different gut microbial communities correlate with efficacy of albendazole-ivermectin against soil-transmitted helminthiases

Soil-transmitted helminth infections represent a large burden with over a quarter of the world's population at risk. Low cure rates are observed with standard of care (albendazole); therefore, a more effective combination therapy (albendazole and ivermectin) is being investigated but showed variable treatment efficacies without evidence of intrinsic parasite resistance. Here, we analyzed the microbiome of Trichuris trichiura and hookworm-infected patients and found an association of different enterotypes with treatment efficacy. 80 T. trichiura-infected patients with hookworm co-infections from Pak-Khan, Laos, received either albendazole (n = 41) or albendazole and ivermectin combination therapy (n = 39). Pre-/post-treatment stool samples were collected to monitor treatment efficacy and microbial communities were profiled using 16S rRNA gene sequencing, qPCR, and shotgun sequencing. We identified three bacterial enterotypes and show that pre-treatment enterotype is associated with efficacy of the combination treatment for both T. trichiura (CRET1 = 5.8%; CRET2 = 16.6%; CRET3 = 68.8%) and hookworm (CRET1 = 31.3%; CRET2 = 16.6%; CRET3 = 78.6%). This study shows that pre-treatment enterotype enables predicting treatment outcome of combination therapy for T. trichiura and hookworm infections.Trial registration: ClinicalTrials.gov, NCT03527732. Registered 17 May 2018, https://clinicaltrials.gov/ct2/show/NCT03527732

Receiver design for the REACH global 21-cm signal experiment

We detail the the REACH radiometric system designed to enable measurements of the 21-cm neutral hydrogen line. Included is the radiometer architecture and end-to-end system simulations as well as a discussion of the challenges intrinsic to highly-calibratable system development. Following this, we share laboratory results based on the calculation of noise wave parameters utilising an over-constrained least squares approach demonstrating a calibration RMSE of 80 mK for five hours of integration on a custom-made source with comparable impedance to that of the antenna used in the field. This paper therefore documents the state of the calibrator and data analysis in December 2022 in Cambridge before shipping to South Africa.Comment: 30 pages, 19 figure

Backtracking and Mixing Rate of Diffusion on Uncorrelated Temporal Networks

We consider the problem of diffusion on temporal networks, where the dynamics of each edge is modelled by an independent renewal process. Despite the apparent simplicity of the model, the trajectories of a random walker exhibit non-trivial properties. Here, we quantify the walker's tendency to backtrack at each step (return where he/she comes from), as well as the resulting effect on the mixing rate of the process. As we show through empirical data, non-Poisson dynamics may significantly slow down diffusion due to backtracking, by a mechanism intrinsically different from the standard bus paradox and related temporal mechanisms. We conclude by discussing the implications of our work for the interpretation of results generated by null models of temporal networks

Rock-paper-scissors dynamics from random walks on temporal multiplex networks

We study diffusion on a multiplex network where the contact dynamics between the nodes is governed by a random process and where the waiting-time distribution differs for edges from different layers. We study the impact on a random walk of the competition that naturally emerges between the edges of the different layers. In opposition to previous studies, which have imposed a priori inter-layer competition, the competition is here induced by the heterogeneity of the activity on the different layers. We first study the precedence relation between different edges and by extension between different layers, and show that it determines biased paths for the walker. We also discuss the emergence of cyclic, rock–paper–scissors effects on random walks, when the precedence between layers is non-transitive. Finally, we numerically show the slowing-down effect due to the competition on a multiplex network with heterogeneous layers activity as the walker is likely to be trapped for a longer time either on a single layer, or on an oriented cycle

Apoptosis in human term placenta is not increased during labor but can be massively induced in vitro

Apoptosis in human placental villi is reported to increase until close to delivery. However, the involvement of the apoptotic process in the initiation of labor, and more particularly in relation to the decrease in placental perfusion during uterine contractions, remains unknown. The purpose of the study was to examine the reactivity of the apoptotic machinery in term placentae obtained before or after the onset of labor and after in vitro incubations. The incidence of apoptotic nuclei (< 1%) as evidenced by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method, and the histological distribution of immunoreactive Bcl-2, Bar, and Bcl-x proteins, were similar in placentae collected after delivery and before the onset of labor and in placental explants maintained overnight at 4 degrees C in a minimal salt-Hepes medium. By contrast, 28% of nuclei contained fragmented DNA when placental explants were incubated overnight at 37 degrees C. This marked increase was associated with a decrease in the intensity of the Bcl-2 immunostaining and an increase in the intensity of Bar and Bcl-x immunostaining. In conclusion, the present study clearly evidences the presence of an active apoptotic machinery in term placental cells that is not involved in normal parturition

Urinary neutral endopeptidase in workers exposed to cadmium: interaction with cigarette smoking.

OBJECTIVES: Structural impairment of the renal proximal tubular epithelium induced by cadmium (Cd) was investigated by measuring the concentration of neutral endopeptidase 24.11 (NEP), an ectoenzyme of the apical brush border, in the urine of 106 male workers employed in a Cd smelter (among whom 52 were occupationally exposed to Cd), and by comparing it with other tubular markers (low molecular weight proteins, lysosomal enzymes). METHODS: NEP (EC 3.4.24.11), beta-N-acetyl-glucosaminidase (NAG) (EC 3.2.1.30), and NAG-B isoenzyme activities were measured by fluorimetric assays, whereas the concentrations of retinol binding protein (RBP), beta 2-microglobulin (beta 2M), and Clara cell protein (CC16) were measured by automated latex agglutination techniques. RESULTS: An increased urinary excretion of NEP as well as microproteins was found only in subjects excreting more than 5 micrograms Cd/g creatinine. In this group, NEP concentrations were significantly higher in the subjects who smoked. This significant interaction could not be found for any other marker tested. CONCLUSIONS: The data suggest that NEP enzymuria is high even at low exposures to Cd (with a threshold of urinary cadmium excretion (U-Cd) at 5 micrograms/g creatinine), indicating early structural alterations. Moreover, its particular sensitivity to smoking could be useful in the detection of new population clusters potentially more susceptible to development of nephrotoxic insult