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RATIONALE: Recreational and medical use of stimulants is increasing, and their use may increase susceptibility to aging and promote neurobehavioral impairments. The long-term consequences of these psychostimulants and how they interact with age have not been fully studied. OBJECTIVES: Our study investigated whether chronic exposure to the prototypical psychostimulant, methamphetamine (METH), at doses designed to emulate human therapeutic dosing, would confer a pro-oxidizing redox shift promoting long-lasting neurobehavioral impairments. METHODS: Groups of 4-month-old male and female C57BL/6J mice were administered non-contingent intraperitoneal injections of either saline or METH (1.4 mg/kg) twice a day for 4 weeks. Mice were randomly assigned to one experimental group: (i) short-term cognitive assessments (at 5 months), (ii) long-term cognitive assessments (at 9.5 months), and (ii) longitudinal motor assessments (at 5, 7 and 9 months). Brain regions were assessed for oxidative stress and markers of neurotoxicity after behavior testing. RESULTS: Chronic METH exposure induced short-term effects on associative memory, gait speed, dopamine (DA) signaling, astrogliosis in females and spatial learning and memory, balance, DA signaling, and excitotoxicity in males. There were no long-term effects of chronic METH on cognition, however, it decreased markers of excitotoxicity in the striatum and exacerbated age-associated motor impairments in males. CONCLUSION: In conclusion, cognitive and motor function were differentially and sex-dependently affected by METH exposure, and oxidative stress did not seem to play a role in the observed behavioral outcomes. Future studies are necessary to continue exploring the long-term neurobehavioral consequences of drug use in both sexes and the relationship between aging and drugs.

Hearing loss (ototoxicity) is a major adverse effect of cisplatin and carboplatin chemotherapy. The aim of this study is to identify novel genetic variants that play a role in platinum-induced ototoxicity. Therefore, a genome-wide association study was performed in the Genetics of Childhood Cancer Treatment (GO-CAT) cohort (n = 261) and the United Kingdom Molecular Genetics of Adverse Drug Reactions in Children Study (United Kingdom MAGIC) cohort (n = 248). Results of both cohorts were combined in a meta-analysis. In primary analysis, patients with SIOP Boston Ototoxicity Scale grade ≥1 were considered cases, and patients with grade 0 were controls. Variants with a p-value −5 were replicated in previously published data by the PanCareLIFE cohort (n = 390). No genome-wide significant associations were found, but variants in TSPAN5, RBBP4P5, AC010090.1 and RNU6-38P were suggestively associated with platinum-induced ototoxicity. The lowest p-value was found for rs7671702 in TSPAN5 (odds ratio 2.0 (95% confidence interval 1.5–2.7), p-value 5.0 × 10−7). None of the associations were significant in the replication cohort, although the effect directions were consistent among all cohorts. Validation and functional understanding of these genetic variants could lead to more insights in the development of platinum-induced ototoxicity.

Insect-associated fungi play an important role in wild and agricultural communities. We present a draft genome sequence of an entomopathogenic strain from the fungal genus Aspergillus , isolated from a honey bee pupa.

Understanding how altered temperature regimes affect harmful cyanobacterial bloom formation is essential for managing aquatic ecosystems amidst ongoing climate warming. This is difficult because algal performance can depend on both current and past environments, as plastic physiological changes (acclimation) may lag behind environmental change. Here, we investigate how temperature variation on sub‐weekly timescales affects population growth and toxin production given acclimation. We studied four ecologically important freshwater cyanobacterial strains under low‐ and high‐nutrient conditions, measuring population growth rate after acclimation and new exposure to a range of temperatures. Cold‐acclimated populations (15.7°C) outperformed fully acclimated populations (held in constant conditions) across 65% of thermal environments, while hot‐acclimated populations (35.7–42.6°C) underperformed across 75% of thermal environments. Over a 5‐day period, cold‐acclimated Microcystis aeruginosa produced ~2.5‐fold more microcystin than hot‐acclimated populations experiencing the same temperature perturbation. Our results suggest that thermal variation and physiology interact in underappreciated ways to influence cyanobacterial growth, toxin production, and likely bloom formation.

Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50 and 70 years, the consequences are bound to be devastating. While age and longevity are the main risk factors for neurodegenerative diseases, sex is also an important risk factor. The characteristic of sex is multifaceted, encompassing sex chromosome complement, sex hormones (estrogens and androgens), and sex hormone receptors. Sex hormone receptors can induce various signaling cascades, ranging from genomic transcription to intracellular signaling pathways that are dependent on the health of the cell. Oxidative stress, associated with aging, can impact the health of the cell. Sex hormones can be neuroprotective under low oxidative stress conditions but not in high oxidative stress conditions. An understudied sex hormone receptor that can induce activation of oxidative stress signaling is the membrane androgen receptor (mAR). mAR can mediate nicotinamide adenine dinucleotide-phosphate (NADPH) oxidase (NOX)-generated oxidative stress that is associated with several neurodegenerative diseases, such as Alzheimer disease. Further complicating this is that aging can alter sex hormone signaling. Prior to menopause, women experience more estrogens than androgens. During menopause, this sex hormone profile switches in women due to the dramatic ovarian loss of 17β-estradiol with maintained ovarian androgen (testosterone, androstenedione) production. Indeed, aging men have higher estrogens than aging women due to aromatization of androgens to estrogens. Therefore, higher activation of mAR-NOX signaling could occur in menopausal women compared with aged men, mediating the observed sex differences. Understanding of these signaling cascades could provide therapeutic targets for neurodegenerative diseases.

This paper considers a real options model with incomplete information in a duopoly setting. I show that even in the presence of a first-mover advantage, there are circumstances in which the preemption region is eroded entirely and the only equilibrium strategy is of simultaneous-type: both players should exercise together or not at all. This outcome arises if the price paid by a player from exercising the option simultaneously with his competitor (over exercising alone as a Stackelberg leader) is low. Such an outcome has not been previously recognised in the literature. The underlying information structure has been applied in a one-firm setting to a range of different contexts of late, all of which have competitive pressures in practice. As such, the existence of this equilibrium under certain conditions ought to be recognised.

BACKGROUND: This systematic literature review summarizes the impact of smoking on maximal oxygen uptake (maximum V ˙ O 2 ). METHODS: Full-text articles were retrieved if the abstract met the assigned criteria. A total of 9 articles were included in the final review based on the inclusion and exclusion criteria. These included articles assessed the effects of tobacco smoking on maximum V ˙ O 2 values. RESULTS: Half of the articles reported a significant difference in maximum V ˙ O 2 scores between smokers and nonsmokers, with smokers having a lower maximum V ˙ O 2 . The other half of the articles did not identify significant differences between smokers and nonsmokers. One study found a significant difference in maximum V ˙ O 2 in only one age group (ie, 20–29 y), but not any of the other age groups. CONCLUSIONS: More research is needed on the effects of smoking on maximum V ˙ O 2 to better understand any relationships or causations.

In this study, we investigate the impact of sea fog over the Yellow Sea on air quality with the direct effect of aerosols for the entire year of 2016. Using the WRF-CMAQ two-way coupled model, we perform four model simulations with the up-to-date emission inventory over East Asia and dynamic chemical boundary conditions provided by hemispheric model simulations. During the spring of 2016, prevailing westerly winds and anticyclones caused the formation of a temperature inversion over the Yellow Sea, providing favorable conditions for the formation of fog. The inclusion of the direct effect of aerosols enhanced its strength. On foggy days, we find dominant changes of aerosols at an altitude of 150–200 m over the Yellow Sea resulted by the production through aqueous chemistry (~12.36% and ~3.08% increases in sulfate and ammonium) and loss via the wet deposition process (~-2.94% decrease in nitrate); we also find stronger wet deposition of all species occurring in PBL. Stagnant conditions associated with reduced air temperature caused by the direct effect of aerosols enhanced aerosol chemistry, especially in coastal regions, and it exceeded the loss of nitrate. The transport of air pollutants affected by sea fog extended to a much broader region. Our findings show that the Yellow Sea acts as not only a path of long-range transport but also as a sink and source of air pollutants. Further study should investigate changes in the impact of sea fog on air quality in conjunction with changes in the concentrations of aerosols and the climate.

In recent years behavioural science has quickly become embedded in national level policy making. As the contributions of behavioural science to the UK’s Covid-19 response policies in early 2020 became apparent, a debate emerged in the British media about its involvement. This served as a unique opportunity to capture public discourse and representation of behavioural science in fast-track, high-stake national policy making. Aimed at identifying elements which foster and detract from trust and credibility in emergent scientific contributions to policy making, in study 1 we use corpus linguistics and thematic analysis to map the narrative around the key behavioural science actors and concepts which were discussed in the 650 news articles extracted from the 15 most read British newspapers over the 12-week period surrounding the first hard UK lockdown from March 2020. We report and discuss 1) the salience of key concepts and actors as the debate unfolded, 2) quantified changes in the polarity of the sentiment expressed toward them and their policy application contexts, and 3) patterns of co-occurrence via network analysis. In Study 2, we investigate how salience and sentiment of key themes observed in traditional media discourse tracked on original Twitter chatter (N = 2,187). In Study 3, we complement these findings with a qualitative analysis of the subset of news articles which contained the most extreme sentiments (N = 111), providing an in-depth perspective of sentiments and discourse developed around keywords, as either promoting or undermining their credibility in, and trust toward behaviourally informed policy. We discuss our findings in light of the integration of behavioural science in national policy making under emergency constraints.

Herefordshire Archaeology undertook a trial trench evaluation between September and November 2018 to investigate a possible defensive ditch, which encircles Breinton Camp, an enigmatic ringwork located southwest of St Michael's Church, Breinton on the northern banks of the River Wye, near Hereford. This feature, which runs under the Norman Church, was discovered through lidar survey and is a possible indication of fortified origins of Breinton Camp, of which the central tump had been used for a house for the Dean and Chaplain of the Hereford Cathedral in c.1150. The evaluation consisted of a single trench, which identified a bank and ditch feature. The bank consisted of layers of turf stacked to form the earthwork packed around a solid clay core. The ditch contained several river cobbles, which may have originally formed a stone facing of the bank. Deposited at the base of the ditch, within the primary fill, the cobbles appear to have been used to build possible corn drying ovens, identified from a significant amount of burnt ceramic building material. In the same context as these cobbles, early medieval pottery was discovered. The upper layers of the ditch were full of later period material related to the construction of Breinton House and subsequent Georgian landscaping. The results suggest the Breinton Camp predates its medieval use and may have origins as a defensive fortified site in the early medieval period.

OBJECTIVE: The aim of this review was to summarise the current evidence on the costing of resource use within UK maternity care, in order to facilitate the estimation of incremental resource and cost impacts potentially attributable to maternity care interventions. METHODS: A systematic review of economic evaluations was conducted by searching Medline, the Health Management Information Consortium, the National Health Service (NHS) Economic Evaluations Database, CINAHL and National Institute for Health and Care Excellence (NICE) guidelines for economic evaluations within UK maternity care, published between January 2010 and August 2019 in the English language. Unit costs for healthcare activities provided to women within the antenatal, intrapartum and postnatal period were inflated to 2018-2019 prices. Assessment of study quality was performed using the Quality of Health Economic Analyses checklist. RESULTS: Of 5084 titles or full texts screened, 37 papers were included in the final review (27 primary research articles, 7 review articles and 3 economic evaluations from NICE guidelines). Of the 27 primary research articles, 21 were scored as high quality, 3 as medium quality and 3 were low quality. Variation was noted in cost estimates for healthcare activities throughout the maternity care pathway: for midwife-led outpatient appointment, the range was £27.34-£146.25 (mean £81.78), emergency caesarean section, range was £1056.44-£4982.21 (mean £3508.93) and postnatal admission, range was £103.00-£870.10 per day (mean £469.55). CONCLUSIONS: Wide variation exists in costs applied to maternity healthcare activities, resulting in challenges in attributing cost to maternity activities. The level of variation in cost calculations is likely to reflect the uncertainty within the system and must be dealt with by conducting sensitivity analyses. Nationally agreed prices for granular unit costs are needed to standardise cost-effectiveness evaluations of new interventions within maternity care, to be used either for research purposes or decisions regarding national intervention uptake. PROSPERO REGISTRATION NUMBER: CRD42019145309.

While much is known regarding the effects of immigration for objective outcomes, relatively little is known regarding the effects for perceived well-being. By exploiting spatial and temporal variation in the net-inflows of foreign-born individuals across local areas in England, we examine the relationship between immigration and natives’ subjective well-being as captured by the General Health Questionnaire (GHQ). We find small negative effects overall but that an analysis of the main effects masks significant differences across subgroups, with relatively older individuals, those with below-average household incomes, the unemployed and finally those without any formal educational qualifications experiencing much more substantive well-being losses than others. These observed well-being differentials are congruent with voting patterns evident in the recent UK referendum on EU membership. We put forward perceived as opposed to actual labour market competition and social identity as two potential explanations for the negative well-being impacts of immigration for natives.

In this paper I develop a theoretical framework of irreversible investment under uncertainty in which there is time to build (TTB). The novel aspects of this framework, compared with TTB models in the extant literature, are that the market is incomplete in that not all the uncertainty associated with investing can be diversified away by trading an appropriate spanning asset, and the decision-maker, who acts in the interest of an organisation, is risk averse. I show that models of investment under uncertainty with a TTB, and models of investment under uncertainty with market incompleteness and risk aversion, ought not to be mutually exclusive as they have been in research to date because the recognised results of market incompleteness and risk aversion on the optimal investment strategy are challenged when we incorporate a TTB feature. Conversely, there are also implications on the effect of a TTB when we incorporate market incompleteness and risk aversion. The framework I develop in this paper provides a robust and parsimonious means of facilitating this.

The genus Saccharibacter is currently understudied, with only one described species, Saccharibacter floricola, isolated from a flower. In an effort to better understand the microbes that come in contact with native bee pollinators, we isolated and sequenced four additional strains of Saccharibacter from native bees in the genera Melissodes and Anthophora. These genomes range in size from 2,104,494 to 2,316,791 bp (mean, 2,246,664 bp) and contain between 1,860 and 2,167 (mean, 2,060) protein-coding genes.

The genus Saccharibacter is currently understudied, with only one described species, Saccharibacter floricola , isolated from a flower. In an effort to better understand the microbes that come in contact with native bee pollinators, we isolated and sequenced four additional strains of Saccharibacter from native bees in the genera Melissodes and Anthophora . These genomes range in size from 2,104,494 to 2,316,791 bp (mean, 2,246,664 bp) and contain between 1,860 and 2,167 (mean, 2,060) protein-coding genes.

Fungi are the leading cause of insect disease, contributing to the decline of wild and managed populations1,2. For ecologically and economically critical species, such as the European honey bee (Apis mellifera), the presence and prevalence of fungal pathogens can have far reaching consequences, endangering other species and threatening food security3,4,5. Our ability to address fungal epidemics and opportunistic infections is currently hampered by the limited number of antifungal therapies6,7. Novel antifungal treatments are frequently of bacterial origin and produced by defensive symbionts (bacteria that associate with an animal/plant host and protect against natural enemies 89. Here we examined the capacity of a honey bee-associated bacterium, Bombella apis, to suppress the growth of fungal pathogens and ultimately protect bee brood (larvae and pupae) from infection. Our results showed that strains of B. apis inhibit the growth of two insect fungal pathogens, Beauveria bassiana and Aspergillus flavus, in vitro. This phenotype was recapitulated in vivo; bee brood supplemented with B. apis were significantly less likely to be infected by A. flavus. Additionally, the presence of B. apis reduced sporulation of A. flavus in the few bees that were infected. Analyses of biosynthetic gene clusters across B. apis strains suggest antifungal production via a Type I polyketide synthase. Secreted metabolites from B. apis alone were sufficient to suppress fungal growth, supporting this hypothesis. Together, these data suggest that B. apis protects bee brood from fungal infection by the secretion of an antifungal metabolite. On the basis of this discovery, new antifungal treatments could be developed to mitigate honey bee colony losses, and, in the future, could address fungal epidemics in other species.