Novel methods for the control of phlebotomine sand flies (Diptera: Psychodidae)

In arid and semi-arid parts of the Old World, Phlebotomus paptasi is a significant biting pest of man and is the primary vector of Leishmania major, the causative agent of zoonotic cutaneous leishmaniasis (ZCL). Phlebotomus papatasi exhibits a close association with the burrowing rodents that serve as the reservoirs of L. major. Rodent burrows are considered to be the primary habitat of immature P. papatasi in ZCL foci, and sand fly larvae have been observed feeding on rodent feces. In laboratory studies, five insecticides (diflubenzuron, novaluron, methoprene, pyriproxyfen, or ivermectin) were incorporated into the diet of Syrian hamsters and evaluated as feed-throughs to control immature sand flies. Feces of hamsters fed a diet containing approximately 10 mg/kg diflubenzuron, novaluron, or pyriproxyfen, or 20 mg/kg ivermectin killed 100% of sand fly larvae that consumed these feces. Feces of hamsters fed a diet containing up to 978.8 mg/kg methoprene caused significant, but not complete, mortality of sand fly larvae. Feces of novaluron-treated hamsters also were held under simulated field conditions for up to 30 d, and all larvae that consumed these feces died before pupation; a significant reduction in treated larval survival relative to control was observed when the feces were aged for up to 150 d. Novaluron also was shown to be effective as a feed-though larvicide when novaluron-treated food made up only a portion of the diet of hamsters. Ivermectin also was evaluated as a systemic insecticide; ivermectin treatment of hamsters was 100% effective against bloodfeeding sand flies for up to 7 d after hamsters were withdrawn from ivermectin-treated diets. In the final study, proof of concept was established for a novel biomarker system using a feed-through fluorescent dye. The value of this method is that it can mark rodents and their feces to establish the consumption of treated-baits, mark adult female sand flies that feed rodents for the duration of persistence of the dye in rodents, and mark adult male and female sand flies that had fed on feces of bait-fed rodents as larvae

Interplay of Environmental Pollutants and Folate in the Etiology of Autistic Traits Analysis Using Multipollutant Approaches

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a spectrum of communication deficits and repetitive behaviors. The challenges in learning, thinking, and problem-solving abilities of people with ASD can be debilitating. There is currently no cure for ASD. Many environmental pollutants are suspected to contribute to the etiology of ASD and its associated traits, whereas folate and folate supplements have been shown to exhibit both protective and adjuvant roles. Little is known about the interplay of multiple environmental pollutants and folate in the etiology of ASD. Additionally, statistical approaches that consider the effects of pollutant mixtures instead single pollutant approaches and establishing the appropriate windows of susceptibility of these pollutants are needed when assessing the relationship between environmental pollutants and health outcomes. Methods: In order to examine the interplay between environmental pollutants, folate, and autistic traits, ExWAS (Exposome Wide Association Study), BKMR (Bayesian Kernel Machine regression), and QgComp (Quantile G Computation) were used. These methods consider many of the challenges associated with pollutants mixtures. The data sources used in this study were the NHANES (National Health and Nutrition Examination Survey) and GUSTO (Growing Up in Singapore Toward healthy Outcomes) cohort. Results: Many environmental pollutants were inversely associated with decreased folate, and autistic traits. Additionally, many environmental pollutants were both positively and inversely associated with autistic traits, and these associations often depended on sex. Finally, folate did modify the associations between some environmental pollutant mixtures and autistic traits, including phthalates, PFAS, and benzophenones. Conclusions: This study highlights the importance for continued research on the etiology of autism. The novel findings of this study inform future epidemiologic analyses of the importance of sex-specific associations between environmental pollutants and autistic traits, and the importance of pollutant mixtures approaches and nutrients when considering such associations. The exploration of new mechanistic pathways between environmental pollutants and autistic traits through folate opens new avenues for future research. Finally, this dissertation provides further evidence that harmful environmental pollutants remain ubiquitous pollutants and remain a threat to public health. Although the results of this dissertation are modest, population level-influence depends on the magnitude of its impact on health and distribution of the factor. Given the ubiquitous exposure to environmental pollutants these modest effect sizes may have a considerable impact on populations

Laboratory evaluation of oral treatment of rodents with systemic insecticides for control of bloodfeeding sand flies (Diptera: Psychodidae)

The purpose of this study was to evaluate the efficacy of oral treatment of rodents with diets containing the systemic insecticides ivermectin, abamectin, imidacloprid, or spinosad, to control bloodfeeding sand flies. We found that diets containing concentrations higher than 10 mg/kg abamectin were not palatable to rodents, and that a diet containing 10 mg/kg abamectin (a palatable concentration) did not cause 100% mortality of bloodfeeding sand flies. Treatment of rodents with imidacloprid was effective for less than 3 days post-treatment. Treatment of rodents with diets containing 20 mg/kg ivermectin or 5000 mg/kg spinosad caused 100% mortality of bloodfeeding sand flies for at least 1 week. The efficacy of ivermectin and spinosad also were not reduced when combined with the fluorescent tracer dye rhodamine B in a single diet. We also did not observe significant benefits by increasing the feeding period of the rodents from 3 to 6 or 9 days. We conclude that ivermectin and spinosad are effective as rodent systemic insecticides against bloodfeeding sand flies, and suggest that weekly treatment of wild rodent reservoirs of Leishmania major with bait containing one of these systemic insecticides could be a useful tool as part of a sand fly control program. © Copyright 2012, Mary Ann Liebert, Inc. 2012

Polynomial functors and opetopes

We give an elementary and direct combinatorial definition of opetopes in terms of trees, well-suited for graphical manipulation and explicit computation. To relate our definition to the classical definition, we recast the Baez–Dolan slice construction for operads in terms of polynomial monads: our opetopes appear naturally as types for polynomial monads obtained by iterating the Baez–Dolan construction, starting with the trivial monad. We show that our notion of opetope agrees with Leinster's. Next we observe a suspension operation for opetopes, and define a notion of stable opetopes. Stable opetopes form a least fixpoint for the Baez–Dolan construction. A final section is devoted to example computations, and indicates also how the calculus of opetopes is well-suited for machine implementation.48 page(s

Association between blood metals mixtures concentrations and cognitive performance, and effect modification by diet in older US adults

International audienceBackground: Chronic exposure to heavy metals has been associated with adverse neurological outcomes in older adults. Inflammatory processes are suspected as an underlying pathway by which metals exert their neurotoxicity. In parallel, a diet rich in antioxidant and anti-inflammatory components may protect against chronic inflammation. Objectives: We examined the associations of blood concentrations of lead, cadmium, and manganese as a mixture with cognitive performance in older US adults and potential modification of these associations by diet as measured by the Healthy Eating Index 2015 (HEI-2015) and the Adapted Dietary Inflammatory Index (ADII). Methods: We used data on 1,777 adults ≥60 years old from the US National Health and Nutrition Examination Survey (NHANES; 2011-2014). We derived the ADII and the HEI-2015 from two nonconsecutive 24-hour diet recalls. Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning subtest, the animal fluency test, and the Digit Symbol Substitution Test (DSST). We also constructed a composite z-score reflecting overall cognitive performance. We used quantile g-computation to evaluate the joint associations of a mixture of metals with cognitive performance test scores. We also evaluated effect modification by sex and diet quality indices using Cochran Q tests. Results: The median (interquartile range) of blood metals were 0.38 μg/L (0.35), 14.70 μg/L (11.70), and 8.74 μg/L (4.06) for cadmium, lead, and manganese, respectively. Increasing blood concentrations of all metals by one quartile was associated with a decrease in overall cognitive performance (-0.04; 95% confidence interval [CI] = -0.09, 0.02), CERAD (-0.04; 95% CI = -0.12, 0.03), animal fluency (-0.02; 95% CI, -0.11, 0.06), and DSST (-0.05; 95% CI = -0.11, 0.02) test scores. These associations were more pronounced in adults with high pro-inflammatory or low-diet quality and null or positive though imprecise associations in participants with a high anti-inflammatory. These associations also varied by sex with inverse associations in men and positive associations in women. Conclusions: Our findings suggest that adherence to an antioxidant and anti-inflammatory diet may prevent blood metals adverse cognitive effects among older adults. If confirmed, strategies based on diet could provide a potential complementary and efficient approach to counteract effects of environmental pollutants

Efficacy of the spatial repellent product Mosquito Shield™ against wild pyrethroid-resistant Anopheles arabiensis in south-eastern Tanzania

Abstract Background Spatial repellents that create airborne concentrations of an active ingredient (AI) within a space offer a scalable solution to further reduce transmission of malaria, by disrupting mosquito behaviours in ways that ultimately lead to reduced human-vector contact. Passive emanator spatial repellents can protect multiple people within the treated space and can last for multiple weeks without the need for daily user touchpoints, making them less intrusive interventions. They may be particularly advantageous in certain use cases where implementation of core tools may be constrained, such as in humanitarian emergencies and among mobile at-risk populations. The purpose of this study was to assess the efficacy of Mosquito Shield™ deployed in experimental huts against wild, free-flying, pyrethroid-resistant Anopheles arabiensis mosquitoes in Tanzania over 1 month. Methods The efficacy of Mosquito Shield™ transfluthrin spatial repellent in reducing mosquito lands and blood-feeding was evaluated using 24 huts: sixteen huts were allocated to Human Landing Catch (HLC) collections and eight huts to estimating blood-feeding. In both experiments, half of the huts received no intervention (control) while the remaining received the intervention randomly allocated to huts and remained fixed for the study duration. Outcomes measured were mosquito landings, blood-fed, resting and dead mosquitoes. Data were analysed by multilevel mixed effects regression with appropriate dispersion and link function accounting for volunteer, hut and day. Results Landing inhibition was estimated to be 70% (57–78%) [IRR 0.30 (95% CI 0.22–0.43); p < 0.0001] and blood-feeding inhibition was estimated to be 69% (56–79%) [IRR 0.31 (95% CI 0.21–0.44; p < 0.0001] There was no difference in the protective efficacy estimates of landing and blood-feeding inhibition [IRR 0.98 (95% CI 0.53–1.82; p = 0.958]. Conclusions This study demonstrated that Mosquito Shield™ was efficacious against a wild pyrethroid-resistant strain of An. arabiensis mosquitoes in Tanzania for up to 1 month and could be used as a complementary or stand-alone tool where gaps in protection offered by core malaria vector control tools exist. HLC is a suitable technique for estimating bite reductions conferred by spatial repellents especially where direct blood-feeding measurements are not practical or are ethically limited