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

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

High locomotor reactivity to novelty is associated with an increased propensity to choose saccharin over cocaine: new insights into the vulnerability to addiction.

Drug addiction is associated with a relative devaluation of natural or socially-valued reinforcers that are unable to divert addicts from seeking and consuming the drug. Before protracted drug exposure, most rats prefer natural rewards, such as saccharin, over cocaine. However, a subpopulation of animals prefer cocaine over natural rewards and are thought to be vulnerable to addiction. Specific behavioral traits have been associated with different dimensions of drug addiction. For example, anxiety predicts loss of control over drug intake whereas sensation seeking and sign-tracking are markers of a greater sensitivity to the rewarding properties of the drug. However, how these behavioral traits predict the disinterest for natural reinforcers remains unknown. In a population of rats, we identified sensation seekers (HR) on the basis of elevated novelty-induced locomotor reactivity, high anxious rats (HA) based on the propensity to avoid open arms in an elevated-plus maze and sign-trackers (ST) that are prone to approach, and interaction with, reward-associated stimuli. Rats were then tested on their preference for saccharin over cocaine in a discrete-trial choice procedure. We show that HR rats display a greater preference for saccharin over cocaine compared with ST and HA whereas the motivation for the drug was comparable between the three groups. The present data suggest that high locomotor reactivity to novelty, or sensation seeking, by predisposing to an increased choice toward non-drug rewards at early stages of drug use history, may prevent the establishment of chronic cocaine use.This work was funded by an INSERM AVENIR and Agence Nationale de la Recherche (ANR) ANR12 SAMA00201 grant to DB, the région Poitou-Charentes, an AXA research fund fellowship to ABR, and a Ministère de la Recherche et de la Technologie grant to NV. AM was supported by the Behavioural and Clinical Neuroscience Institute of Cambridge.This is the accepted manuscript of a paper published in Neuropsychopharmacology (2015) 40, 577–589; doi:10.1038/npp.2014.204; published online 17 September 2014

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents.

Acetylcholinesterase inhibitors (ChEIs) enhance neuronal transmission by increasing the availability of acetylcholine in muscarinic and nicotinic receptors. This effect is believed to be responsible for the beneficial and protective effects of ChEIs on cognition in patients with Alzheimer's disease (AD). Effects of ChEIs on mood and behavior have also been reported. Earlier observations were limited by the exclusive availability of intravenous forms of administration, the short half-life of the formulations, and the high frequency of peripheral side effects. The introduction, in recent years, of better tolerated and less invasive compounds has rekindled the interest in cholinergic central nervous system mechanisms and has given rise to studies in areas other than cognition. The ChEI donepezil has been involved in the largest number of studies and positive reports. Preliminary observations suggest the possible value of ChEIs in the management of behavioral dysregulation, apathy, irritability, psychosis, depression, mania, tics, and delirium and in the diagnosis of depression, panic, and personality disorders

Subtle effects of environmental stress observed in the early life stages of the Common frog, Rana temporaria

Worldwide amphibian populations are declining due to habitat loss, disease and pollution. Vulnerability to environmental contaminants such as pesticides will be dependent on the species, the sensitivity of the ontogenic life stage and hence the timing of exposure and the exposure pathway. Herein we investigated the biochemical tissue ‘fingerprint’ in spawn and early-stage tadpoles of the Common frog, Rana temporaria, using attenuated total reflection- Fourier-transform infrared (ATR-FTIR) spectroscopy with the objective of observing differences in the biochemical constituents of the respective amphibian tissues due to varying water quality in urban and agricultural ponds. Our results demonstrate that levels of stress (marked by biochemical constituents such as glycogen that are involved in compensatory metabolic mechanisms) can be observed in tadpoles present in the pond most impacted by pollution (nutrients and pesticides), but large annual variability masked any inter-site differences in the frog spawn. ATR-FTIR spectroscopy is capable of detecting differences in tadpoles that are present in selected ponds with different levels of environmental perturbation and thus serves as a rapid and cost effective tool in assessing stress-related effects of pollution in a vulnerable class of organism

Appraising the intention of other people: Ecological validity and procedures for investigating effects of lighting for pedestrians

One of the aims of outdoor lighting public spaces such as pathways and subsidiary roads is to help pedestrians to evaluate the intentions of other people. This paper discusses how a pedestrians’ appraisal of another persons’ intentions in artificially lit outdoor environments can be studied. We review the visual cues that might be used, and the experimental design with which effects of changes in lighting could be investigated to best resemble the pedestrian experience in artificially lit urban environments. Proposals are made to establish appropriate operationalisation of the identified visual cues, choice of methods and measurements representing critical situations. It is concluded that the intentions of other people should be evaluated using facial emotion recognition; eye tracking data suggest a tendency to make these observations at an interpersonal distance of 15 m and for a duration of 500 ms. Photographs are considered suitable for evaluating the effect of changes in light level and spectral power distribution. To support investigation of changes in spatial distribution further investigation is needed with 3D targets. Further data are also required to examine the influence of glare

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Coalition governance and foreign policy decision making

This article explores processes of coalition governance in foreign policy. Specifically, it argues that such processes are shaped by two interrelated dimensions of coalition set-up: first, the allocation of the foreign ministry to the senior or a junior coalition partner and, second, the degree of policy discretion which is delegated to that ministry. Bringing these two dimensions together, the article distinguishes four types of coalition arrangement for the making of foreign policy, which are expected to have predictable implications for the process of foreign policy-making and, ultimately, for the foreign policy outputs of multi-party coalitions and their quality

Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

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