Do topical repellents divert mosquitoes within a community? Health equity implications of topical repellents as a mosquito bite prevention tool.

OBJECTIVES: Repellents do not kill mosquitoes--they simply reduce human-vector contact. Thus it is possible that individuals who do not use repellents but dwell close to repellent users experience more bites than otherwise. The objective of this study was to measure if diversion occurs from households that use repellents to those that do not use repellents. METHODS: The study was performed in three Tanzanian villages using 15%-DEET and placebo lotions. All households were given LLINs. Three coverage scenarios were investigated: complete coverage (all households were given 15%-DEET), incomplete coverage (80% of households were given 15%-DEET and 20% placebo) and no coverage (all households were given placebo). A crossover study design was used and coverage scenarios were rotated weekly over a period of ten weeks. The placebo lotion was randomly allocated to households in the incomplete coverage scenario. The level of compliance was reported to be close to 100%. Mosquito densities were measured through aspiration of resting mosquitoes. Data were analysed using negative binomial regression models. FINDINGS: Repellent-users had consistently fewer mosquitoes in their dwellings. In villages where everybody had been given 15%-DEET, resting mosquito densities were fewer than half that of households in the no coverage scenario (Incidence Rate Ratio [IRR]=0.39 (95% confidence interval [CI]: 0.25-0.60); p<0.001). Placebo-users living in a village where 80% of the households used 15%-DEET were likely to have over four-times more mosquitoes (IRR=4.17; 95% CI: 3.08-5.65; p<0.001) resting in their dwellings in comparison to households in a village where nobody uses repellent. CONCLUSIONS: There is evidence that high coverage of repellent use could significantly reduce man-vector contact but with incomplete coverage evidence suggests that mosquitoes are diverted from households that use repellent to those that do not. Therefore, if repellents are to be considered for vector control, strategies to maximise coverage are required

Reappraising Threat: How to Optimize Performance Under Pressure

Competitive situations often hinge on one pressurized moment. In these situations, individuals' psychophysiological states determine performance, with a challenge state associated with better performance than a threat state. But what can be done if an individual experiences a threat state? This study examined one potential solution: arousal reappraisal. Fifty participants received either arousal reappraisal or control instructions before performing a pressurized, single-trial, motor task. Although both groups initially displayed cardiovascular responses consistent with a threat state, the reappraisal group displayed a cardiovascular response more reflective of a challenge state (relatively higher cardiac output and/or lower total peripheral resistance) after the reappraisal manipulation. Furthermore, despite performing similarly at baseline, the reappraisal group outperformed the control group during the pressurized task. The results demonstrate that encouraging individuals to interpret heightened physiological arousal as a tool that can help maximize performance can result in more adaptive cardiovascular responses and motor performance under pressure

Evidence for the horizontal acquisition of murine AKR virogenes by recent horizontal infection of the germ line

Several recent reports (8, 10, 11, 13) have established the biological and molecular genetic similarity between the endogenous AKV virus of strain AKR, and an N-ecotropic endogenous virus found in the genome of feral Japanese mice, Mus musculus molossinus. The similarities are so striking as to suggest a common origin of these viruses, which are present in some, but not all, inbred mouse strains. The virogenes of AKR mice may have been acquired by either: (a) common descent of AKR (and other AKV(+) strains) from a common ancestor of AKR and molossinus animals, or (b) horizontal germ line infection of the AKR strains by molossinus virus at 1;he strain’s inception followed by fixation through inbreeding. The sexual descent model carries with it a prediction of relative consanguinity of the AKR strain and molossinus, whereas the horizontal infection model does not. We have examined the polymorphic allozyme (allelic isozyme) genotype of 51 nonvirus-related loci in 17 strains of mice including AKR, C58, BALB/c, Swiss, and molossinus. By comparing the composite allozyme genotype of different inbred and outbred mouse strains, the “genetic distance” statistic was derived. Genetic distance measures the degree of allelic substitution between populations and increases proportionately with the amount of time the populations have been reproductively isolated. The genetic distance computed between molossinus and AKR is large, nearly 5-10 times the distance between known related populations and strains (e.g., C57L vs. C57BL/6). Molossinus had a similarly large distance from AKV negative strains (Swiss, C57L) as it did from AKV- positive strains. Cellular DNA sequences that flank the integrated AKV provirus were analyzed by restriction enzyme digestion of liver DNA from molossinus, AKR, and additional inbred strains that express ecotropic murine leukemia virus. The integration flanks of three AKR provirus sequences, Akv-1, Akv-2, and a third uncharacterized sequence, were not evident in molossinus cell DNA, which contained at least six different proviral integration fragments. These data effectively exclude the interpretation of consanguinity of AKR and molossinus and support the notion of acquisition of the endogenous virus in AKR by horizontal infection of the molossinus virus

The regulatory logic of Pax3 expression in the neural tube

The development of complex tissues is dependent on the specification and maintenance of distinct transcriptional identities within populations of equivalent progenitors. In the vertebrate neural tube, progenitor identity is specified by the spatially organised expression of transcription factors within the dorso-ventral (DV) axis of the tissue. A series of selective cross-repressive interactions between transcription factors expressed in adjacent domains forms the basis of a gene regulatory network (GRN), which acts to define and maintain the boundaries between progenitor populations. Pax3 is a key member of the neural tube GRN that is transcribed throughout the dorsal domains of the spinal cord and exhibits a ventral boundary of expression at the level of the sulcus limitans. The regulatory mechanisms that induce Pax3 transcription in neural progenitors and subsequently produce a sharp ventral boundary of gene expression are poorly understood. Using a genetic lineage tracing strategy in mice, we show that the position of the Pax3 expression domain is established within the neural plate and subsequently maintained throughout spinal cord development. Additionally, we demonstrate that V0 interneuron progenitors transiently express Pax3 during their early development. We employ a comparative genomics based approach to investigate the molecular basis of Pax3 transcription, revealing several novel enhancers associated with the locus. Functional dissection of an early central nervous system (CNS) specific enhancer supports the role of the Wnt signaling pathway in the induction of Pax3 transcription. Furthermore, we establish the function of direct transcriptional repression in the establishment of the Pax3 expression domain. Analysis of a second CNS specific enhancer reveals that Pax3 expression is dependent on autoregulation and Pax7 mediated positive feedback post-neurulation. Together, these data indicate that the temporal activity of two distinct enhancers underlies the regulatory logic of Pax3 expression in the neural tube

A methodology for developing plant-based mosquito biocides

In the South American and Southeast Asian forests, the Anopheles mosquito malaria vectors bite outdoors early in the evening, and rest outdoors. These behaviours preclude complete control by insecticides and bednets. Personal protection is necessary to protect from drug-resistant malaria. The thesis investigates the development of novel, plant-based mosquito control and personal protection: 1) discovery of new, culturally acceptable plants, 2) laboratory testing of those plants and 3) field testing of efficacious candidates as revealed by laboratory testing. Focus is upon on development of robust methodologies for the laboratory and field that carefully consider Anopheles behaviour to minimise bias. In Phase 1, an ethnobotanical survey in Yunnan, China, investigating knowledge, attitudes and practise about malaria and personal protection, several potentially insecticidal plants traditionally used against insects were identified. Knowledge of malaria was low, but everyone used personal protection at home, but not outdoors, to prevent nuisance biting. The expense of personal protection precluded use and the incorporation of plants into a low-cost insect repellent or mosquito coil would be acceptable for Yunnan. In Phase 2, a laboratory evaluation of neem (Azadirachta indica) as a larvicide, oviposition kairomone and bednet treatment, several assay methods were compared. WHO methodologies proved robust, and should be used as gold standards. When testing oviposition kairomones, choice tests should be run parallel with no-choice tests, as Anopheles mosquitoes oviposit in sub-optimal substrates in the absence of choice. A novel laboratory assay representing a normal exposure of bednet treatment to host-seeking mosquitoes was developed. In Phase 3, a field evaluation of plant based repellents in Bolivia, focus groups and novel repellents were investigated. Volatilisation of repellents proved unsuitable for use in open housing. 20%, of mosquitoes, are diverted from deet repellent-protected to unprotected individuals. The implications for repellent-testing methodology, and repellents as a means of disease control, are discussed

Prescription Drugs Associated with Reports of Violence Towards Others

CONTEXT: Violence towards others is a seldom-studied adverse drug event and an atypical one because the risk of injury extends to others. OBJECTIVE: To identify the primary suspects in adverse drug event reports describing thoughts or acts of violence towards others, and assess the strength of the association. METHODOLOGY: From the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) data, we extracted all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. We identified any case report indicating homicide, homicidal ideation, physical assault, physical abuse or violence related symptoms. MAIN OUTCOME MEASURES: Disproportionality in reporting was defined as a) 5 or more violence case reports, b) at least twice the number of reports expected given the volume of overall reports for that drug, c) a χ2 statistic indicating the violence cases were unlikely to have occurred by chance (p<0.01). RESULTS: We identified 1527 cases of violence disproportionally reported for 31 drugs. Primary suspect drugs included varenicline (an aid to smoking cessation), 11 antidepressants, 6 sedative/hypnotics and 3 drugs for attention deficit hyperactivity disorder. The evidence of an association was weaker and mixed for antipsychotic drugs and absent for all but 1 anticonvulsant/mood stabilizer. Two or fewer violence cases were reported for 435/484 (84.7%) of all evaluable drugs suggesting that an association with this adverse event is unlikely for these drugs. CONCLUSIONS: Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and antidepressants with serotonergic effects were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features

Draft genome sequences of Achromobacter piechaudii GCS2, Agrobacterium sp. Strain SUL3, Microbacterium sp. Strain GCS4, Shinella sp. Strain GWS1, and Shinella sp. Strain SUS2 isolated from Consortium with the Hydrocarbon-Producing Alga Botryococcus braunii.

This is the final version of the article. Available from American Society for Microbiology via the DOI in this record.A variety of bacteria associate with the hydrocarbon-producing microalga Botryococcus braunii, some of which may influence its growth. We report here the genome sequences for Achromobacter piechaudii GCS2, Agrobacterium sp. strain SUL3, Microbacterium sp. strain GCS4, and Shinella sp. strains GWS1 and SUS2, isolated from a laboratory culture of B. braunii, race B, strain Guadeloupe.K.J.J. was funded by a Ph.D. studentship from the Biotechnology and Biologaical Sciences Research Council (BBSRC) LoLa award BB/ K003240/2. The Exeter Sequencing Service was supported by the Wellcome Trust Institutional Strategic Support Fund (WT097835MF), a Wellcome Trust Multi User Equipment Award (WT101650MA), and a BBSRC LoLa award (BB/K003240/2). We gratefully acknowledge the Exeter Sequencing Service and computational core facilities at the University of Exete

DSMC simulations of turbulent flows at moderate Reynolds numbers

The Direct Simulation Monte Carlo (DSMC) method has been used for more than 50 years to simulate rarefied gases. The advent of modern supercomputers has brought higher-density near-continuum flows within range. This in turn has revived the debate as to whether the Boltzmann equation, which assumes molecular chaos, can be used to simulate continuum flows when they become turbulent. In an effort to settle this debate, two canonical turbulent flows are examined, and the results are compared to available continuum theoretical and numerical results for the Navier-Stokes equations

Generation of versatile ss-dsDNA hybrid substrates for single-molecule analysis.

Here, we describe a rapid and versatile protocol to generate gapped DNA substrates for single-molecule (SM) analysis using optical tweezers via site-specific Cas9 nicking and force-induced melting. We provide examples of single-stranded (ss) DNA gaps of different length and position. We outline protocols to visualize these substrates by replication protein A-enhanced Green Fluorescent Protein (RPA-eGFP) and SYTOX Orange staining using commercially available optical tweezers (C-TRAP). Finally, we demonstrate the utility of these substrates for SM analysis of bidirectional growth of RAD-51-ssDNA filaments. For complete details on the use and execution of this protocol, please refer to Belan et al. (2021)