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An extensive body of research using concurrent‐chains schedules of reinforcement has shown that choice for one of two differentially valued food‐associated stimuli is dependent upon the overall temporal context in which those stimuli are embedded. The present experiments examined whether the concurrent chains procedure was useful for the study of behavior maintained by alcohol and alcohol‐associated stimuli. In Experiment 1, rats responded on concurrent‐chains schedules with equal variable‐interval (VI) 10‐s schedules in the initial links. Across conditions, fixed‐interval schedules in the terminal links were varied to yield 1:1, 9:1, and 1:9 ratios of alcohol delivery. Initial‐link response rates reflected changes in terminal‐link schedules, with greater relative responding in the rich terminal link. In Experiment 2, terminal‐link schedules remained constant with a 9:1 ratio of alcohol delivery rates while the length of two equal duration initial‐link schedules was varied. Preference for the rich terminal link was less extreme when initial links were longer (i.e., the initial‐link effect), as has been previously reported with food reinforcers. This result suggests that the conditioned reinforcing value of an alcohol‐associated stimulus depends on the temporal context in which it is embedded. The concurrent‐chains procedure and quantitative models of concurrent chains performance may provide a useful framework within which to study how contextual variables modulate preference for drug‐associated conditioned reinforcers.

Impulsive stress in repeated shock waves administered during extracorporeal shock-wave lithotripsy (ESWL) causes injury to kidney tissue. In a study of the mechanical input of ESWL, the effects of focused shock waves on thin planar polymeric membranes immersed in a variety of tissue-mimicking fluids have been examined. A direct mechanism of failure by shock compression and an indirect mechanism by bubble collapse have been observed. Thin membranes are easily damaged by bubble collapse. After propagating through cavitation-free acoustically heterogeneous media (liquids mixed with hollow glass spheres, and tissue) shock waves cause membranes to fail in fatigue by a shearing mechanism. As is characteristic of dynamic fatigue, the failure stress increases with strain rate, determined by the amplitude and rise time of the attenuated shock wave. Shocks with large amplitude and short rise time (i.e., in uniform media) cause no damage. Thus the inhomogeneity of tissue is likely to contribute to injury in ESWL. A definition of dose is proposed which yields a criterion for damage based on measurable shock wave properties.

Abstract Background Malaria remains one of the most devastating diseases globally, and the control of mosquitoes as the vector is mainly dependent on chemical insecticides. Elevated temperatures associated with future warmer climates could affect mosquitoes' metabolic enzyme expression and increase insecticide resistance, making vector control difficult. Understanding how mosquito rearing temperatures influence their susceptibility to insecticide and expression of metabolic enzymes could aid in the development of novel tools and strategies to control mosquitoes in a future warmer climate. This study evaluated the effects of temperature on the susceptibility of Anopheles gambiae sensu lato (s.l.) mosquitoes to pyrethroids and their expression of metabolic enzymes. Methods Anopheles gambiae s.l. eggs obtained from laboratory-established colonies were reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38, and 40 °C). Upon adult emergence, 3- to 5-day-old female non-blood-fed mosquitoes were used for susceptibility tests following the World Health Organization (WHO) bioassay protocol. Batches of 20–25 mosquitoes from each temperature regime (25–34 °C) were exposed to two pyrethroid insecticides (0.75% permethrin and 0.05% deltamethrin). In addition, the levels of four metabolic enzymes (α-esterase, β-esterase, glutathione S-transferase [GST], and mixed-function oxidase [MFO]) were examined in mosquitoes that were not exposed and those that were exposed to pyrethroids. Results Mortality in An. gambiae s.l. mosquitoes exposed to deltamethrin and permethrin decreased at temperatures above 28 °C. In addition, mosquitoes reared at higher temperatures were more resistant and had more elevated enzyme levels than those raised at low temperatures. Overall, mosquitoes that survived after being exposed to pyrethroids had higher levels of metabolic enzymes than those that were not exposed to pyrethroids. Conclusions This study provides evidence that elevated temperatures decreased An. gambiae s.l. mosquitoes' susceptibility to pyrethroids and increased the expression of metabolic enzymes. This evidence suggests that elevated temperatures projected in a future warmer climate could increase mosquitoes' resistance to insecticides and complicate malaria vector control measures. This study therefore provides vital information, and suggests useful areas of future research, on the effects of temperature variability on mosquitoes that could guide vector control measures in a future warmer climate. Graphical Abstract

BackgroundAlcohol abuse is a risk factor for bone damage and fracture‐related complications. Through precise β‐catenin signaling, canonical Wnt signaling plays a key role in fracture repair by promoting the differentiation of new bone and cartilage cells. In this study, we examined the effects of alcohol on the Wnt pathway in injured bone using a murine model of alcohol‐induced impaired fracture healing.MethodsMale C57Bl/6 or T cell factor (TCF)‐transgenic mice were administered 3 daily intraperitoneal doses of alcohol or saline. One hour following the final injection, mice were subjected to a stabilized, mid‐shaft tibial fracture. Injured and contralateral tibias were harvested at 6, 9, or 14 days post‐fracture for the analysis of biomechanical strength, callus tissue composition, and Wnt/β‐catenin signaling.ResultsAcute alcohol treatment was associated with a significant decrease in fracture callus volume, diameter, and biomechanical strength at day 14 post‐fracture. Histology revealed an alcohol‐related reduction in cartilage and bone formation at the fracture site, and that alcohol inhibited normal cartilage maturation. Acute alcohol exposure caused a significant 2.3‐fold increase in total β‐catenin protein at day 6 and a significant decrease of 53 and 56% at days 9 and 14, respectively. lacZ staining in β‐galactosidase‐expressing TCF‐transgenic mice revealed spatial and quantitative differences in Wnt‐specific transcriptional activation at day 6 in the alcohol group. Days 9 and 14 post‐fracture showed that acute alcohol exposure decreased Wnt transcriptional activation, which correlates with the modulation of total β‐catenin protein levels observed at these time points.ConclusionsAcute alcohol exposure resulted in significant impairment of fracture callus tissue formation, perturbation of the key Wnt pathway protein β‐catenin, and disruption of normal Wnt‐mediated transcription. These data suggest that the canonical Wnt pathway is a target for alcohol in bone and may partially explain why impaired fracture healing is observed in alcohol‐abusing individuals.

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.

AbstractLarge conductance potassium (BK) channels are among the most sensitive molecular targets of ethanol and genetic variations in the channel-forming α subunit have been nominally associated with alcohol use disorders. However, whether the action of ethanol at BK α influences the motivation to drink alcohol remains to be determined. To address this question, we first tested the effect of systemically administered BK channel modulators on voluntary alcohol consumption in C57BL/6J males. Penitrem A (blocker) exerted dose-dependent effects on moderate alcohol intake, while paxilline (blocker) and BMS-204352 (opener) were ineffective. Because pharmacological manipulations are inherently limited by non-specific effects, we then sought to investigate the behavioral relevance of ethanol’s direct interaction with BK α by introducing in the mouse genome a point mutation known to render BK channels insensitive to ethanol while preserving their physiological function. The BK α K361N substitution prevented ethanol from reducing spike threshold in medial habenula neurons. However, it did not alter acute responses to ethanol in vivo, including ataxia, sedation, hypothermia, analgesia, and conditioned place preference. Furthermore, the mutation did not have reproducible effects on alcohol consumption in limited, continuous, or intermittent access home cage two-bottle choice paradigms conducted in both males and females. Notably, in contrast to previous observations made in mice missing BK channel auxiliary β subunits, the BK α K361N substitution had no significant impact on ethanol intake escalation induced by chronic intermittent alcohol vapor inhalation. It also did not affect the metabolic and locomotor consequences of chronic alcohol exposure. Altogether, these data suggest that the direct interaction of ethanol with BK α does not mediate the alcohol-related phenotypes examined here in mice.