The spread of COVID-19 in London: Network effects and optimal lockdowns.

We generalise a stochastic version of the workhorse SIR (Susceptible-Infectious-Removed) epidemiological model to account for spatial dynamics generated by network interactions. Using the London metropolitan area as a salient case study, we show that commuter network externalities account for about 42% of the propagation of COVID-19. We find that the UK lockdown measure reduced total propagation by 44%, with more than one third of the effect coming from the reduction in network externalities. Counterfactual analyses suggest that: (i) the lockdown was somehow late, but further delay would have had more extreme consequences; (ii) a targeted lockdown of a small number of highly connected geographic regions would have been equally effective, arguably with significantly lower economic costs; (iii) targeted lockdowns based on threshold number of cases are not effective, since they fail to account for network externalities.

A prebiotic fiber increases the formation and subsequent absorption of compound K following oral administration of ginseng in rats.

BACKGROUND: Gut microflora play a crucial role in the biotransformation of ginsenosides to compound K (CK), which may affect the pharmacological effects of ginseng. Prebiotics, such as NUTRIOSE, could enhance the formation and consequent absorption of CK through the modulation of gut microbial metabolic activities. In this study, the effect of a prebiotic fiber (NUTRIOSE) on the pharmacokinetics of ginsenoside CK, a bioactive metabolite of ginsenosides, and its mechanism of action were investigated. METHODS: Male Sprague-Dawley rats were given control or NUTRIOSE-containing diets (control diet + NUTRIOSE) for 2 wk, and ginseng extract or vehicle was then orally administered. Blood samples were collected to investigate the pharmacokinetics of CK using liquid chromatography-tandem mass spectrometry. Fecal activities that metabolize ginsenoside Rb1 to CK were assayed with fecal specimens or bacteria cultures. RESULTS: When ginseng extract was orally administered to rats fed with 2.5%, 5%, or 10% NUTRIOSE containing diets, the maximum plasma concentration (C max) and area under the plasma concentration-time curve values of CK significantly increased in a NUTRIOSE content-dependent manner. NUTRIOSE intake increased glycosidase activity and CK formation in rat intestinal contents. The CK-forming activities of intestinal microbiota cultured in vitro were significantly induced by NUTRIOSE. CONCLUSION: These results show that prebiotic diets, such as NUTRIOSE, may promote the metabolic conversion of ginsenosides to CK and the subsequent absorption of CK in the gastrointestinal tract and may potentiate the pharmacological effects of ginseng.

Effect of a soluble prebiotic fiber, NUTRIOSE, on the absorption of ginsenoside Rd in rats orally administered ginseng.

BACKGROUND: There is limited understanding of the effect of dietary components on the absorption of ginsenosides and their metabolites into the blood. METHODS: This study investigated the pharmacokinetics of the ginseng extract and its main constituent ginsenoside Rb1 in rats with or without pretreatment with a prebiotic fiber, NUTRIOSE, by liquid chromatography tandem mass spectrometry. When ginsenoside Rb1 was incubated with rat feces, its main metabolite was ginsenoside Rd. RESULTS: When the intestinal microbiota of rat feces were cultured in vitro, their ginsenoside Rd-forming activities were significantly induced by NUTRIOSE. When ginsenoside Rb1 was orally administered to rats, the maximum plasma concentration (Cmax) and area under the plasma drug concentration-time curve (AUC) for the main metabolite, ginsenoside Rd, were 72.4 ± 31.6 ng/mL and 663.9 ± 285.3 µg·h/mL, respectively. When the ginseng extract (2,000 mg/kg) was orally administered, Cmax and AUC for ginsenoside Rd were 906.5 ± 330.2 ng/mL and 11,377.3 ± 4,470.2 µg·h/mL, respectively. When ginseng extract was orally administered to rats fed NUTRIOSE containing diets (2.5%, 5%, or 10%), Cmax and AUC were increased in the NUTRIOSE receiving groups in a dose-dependent manner. CONCLUSION: These findings reveal that intestinal microflora promote metabolic conversion of ginsenoside Rb1 and ginseng extract to ginsenoside Rd and promote its absorption into the blood in rats. Its conversion may be induced by prebiotic diets such as NUTRIOSE.