Compound-specific Carbon Isotope Compositions of Aldehydes and Ketones in the Murchison Meteorite

Compoundspecific carbon isotope analysis (13C) of meteoritic organic compounds can be used to elucidate the abiotic chemical reactions involved in their synthesis. The soluble organic content of the Murchison carbonaceous chondrite has been extensively investigated over the years, with a focus on the origins of amino acids and the potential role of Streckercyanohydrin synthesis in the early solar system. Previous 13C investigations have targeted amino acid and hydroxy acid Strecker products and reactant HCN; however, 13C values for meteoritic aldehydes and ketones (Strecker precursors) have not yet been reported. As such, the distribution of aldehydes and ketones in the cosmos and their role in prebiotic reactions have not been fully investigated. Here, we have applied an optimized O(2,3,4,5,6pentafluorobenzyl)hydroxylamine (PFBHA) derivatization procedure to the extraction, identification, and 13C analysis of carbonyl compounds in the Murchison meteorite. A suite of aldehydes and ketones, dominated by acetaldehyde, propionaldehyde, and acetone, were detected in the sample. 13C values, ranging from 10.0 to +66.4, were more 13Cdepleted than would be expected for aldehydes and ketones derived from the interstellar medium, based on interstellar 12C/13C ratios. These relatively 13Cdepleted values suggest that chemical processes taking place in asteroid parent bodies (e.g., oxidation of the IOM) may provide a secondary source of aldehydes and ketones in the solar system. Comparisons between 13C compositions of meteoritic aldehydes and ketones and other organic compound classes were used to evaluate potential structural relationships and associated reactions, including Strecker synthesis and alterationdriven chemical pathways

Tonic inhibition of accumbal spiny neurons by extrasynaptic 4 GABAA receptors modulates the actions of psychostimulants

Within the nucleus accumbens (NAc), synaptic GABAA receptors (GABAARs) mediate phasic inhibition of medium spiny neurons (MSNs) and influence behavioral responses to cocaine. We demonstrate that both dopamine D1- and D2-receptor-expressing MSNs (D-MSNs) additionally harbor extrasynaptic GABAARs incorporating α4, β, and δ subunits that mediate tonic inhibition, thereby influencing neuronal excitability. Both the selective δ-GABAAR agonist THIP and DS2, a selective positive allosteric modulator, greatly increased the tonic current of all MSNs from wild-type (WT), but not from δ−/− or α4−/− mice. Coupling dopamine and tonic inhibition, the acute activation of D1 receptors (by a selective agonist or indirectly by amphetamine) greatly enhanced tonic inhibition in D1-MSNs but not D2-MSNs. In contrast, prolonged D2 receptor activation modestly reduced the tonic conductance of D2-MSNs. Behaviorally, WT and constitutive α4−/− mice did not differ in their expression of cocaine-conditioned place preference (CPP). Importantly, however, mice with the α4 deletion specific to D1-expressing neurons (α4D1−/−) showed increased CPP. Furthermore, THIP administered systemically or directly into the NAc of WT, but not α4−/− or α4D1−/− mice, blocked cocaine enhancement of CPP. In comparison, α4D2−/− mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1- and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, α4βδ GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors

The application of mHealth to mental health: opportunities and challenges

Recent advances in smartphones and wearable biosensors enable the gathering of ‘real-time’ psychological, behavioural and physiological data, in increasingly precise and unobtrusive ways. It is therefore now possible to collect moment-to-moment information about an individuals’ moods, cognitions and activities, as well as automated data about their whereabouts, behaviour and physiological states. In this paper, we discuss the potential of these new mobile digital technologies for transforming mental health research and clinical practice. By drawing on a recent research project, we illustrate how traditional boundaries between research and clinical practice are becoming increasingly blurred and how in turn, this is leading to exciting new developments in the assessment and management of common mental disorders. The potential risks and key challenges associated with applying mobile technology to mental health are also discussed

Perceived addiction to smoking and associations with motivation to stop, quit attempts and quitting success: A prospective study of English smokers

Aims: Some argue that perceived addiction to smoking (PAS) might undermine motivation to stop. We examined the association of PAS with motivation to stop in a population sample and assessed its association with past and future quit attempts and future quit success. Method: 12,700 smokers in England were surveyed between September 2009–March 2012 as part of the Smoking Toolkit Study. 2796 smokers were followed up after 6 months. PAS was assessed at baseline by a single self-report item. The outcome variables were ratings of motivation to stop and reports of past-year quit attempts at baseline, and quit attempts in the past 6 months and smoking status at follow-up. Baseline covariates were sex, age, social grade and daily cigarette consumption. Results: In adjusted analyses, PAS was positively associated with at least some degree of motivation to stop versus no motivation (ORs = 1.97–2.96, all p's < 0.001). PAS was also positively associated with past-year quit attempts (OR = 1.43, 95% CI = 1.32–1.55, p < 0.001), but not with future quit attempts (OR = 1.17, 95% CI = 0.99–1.39, p = 0.064) or quit success (OR = 1.04, 95% CI = 0.73–1.47, p = 0.83). Conclusion: In smokers in England, perceived addiction to smoking is positively associated with motivation to stop and having recently made a quit attempt but is not clearly associated with future quit attempts or success. These findings provide no grounds for believing that increasing smokers' perceived addiction through promotion of stop-smoking support has undermined motivation to stop

Does consistent motivation to stop smoking improve the explanation of recent quit attempts beyond current motivation? A cross-sectional study

AIMS: In seeking to provide more accurate models of population quit attempt rates, this study assessed whether a single self-report measure of consistent motivation to stop smoking adds useful explanatory power over and above an established measure of current motivation to stop. METHOD: Data from 16,657 current smokers in England were collected between October 2012 and June 2017 using cross-sectional household surveys. Smokers were asked whether they had made a serious quit attempt in the past year and they answered two questions on motivation to stop (current motivation and consistent motivation to stop smoking). Having made at least one quit attempt in the past year was regressed in logistic models onto current motivation to stop and consistent motivation to stop individually and then together, with both models adjusting for sociodemographic variables and a measure of nicotine dependence. RESULTS: The addition of consistent motivation to stop smoking added substantially to the fit of the model over and above the established measure of current motivation to quit (χ2(1, N = 16,657) = 901.7, p < 0.001) with an adjusted odds ratio of 4.1 (95% CI = 3.7–4.5, p < 0.001). CONCLUSION: Consistent motivation to stop smoking substantially improves the modelling of recent smoking cessation attempts over and above current motivation to stop. The consistency of smokers' motivation to quit may be a useful explanatory and target variable in future intervention studies

Unusual features in the nonlinear microwave surface impedance of Y-Ba-Cu-O thin films

Striking features have been found in the nonlinear microwave (8 GHz) surface impedance $Z_s=R_s + jX_s$ of high-quality YBaCuO thin films with comparable low power characteristics [$R_{res}\sim 35--60 \mu\Omega$ and $\lambda_L(15 K)\sim 130--260 nm$]. The surface resistance $R_s$ is found to increase, decrease, or remain independent of the microwave field $H_{rf}$ (up to 60 mT) at different temperatures and for different samples. However, the surface reactance $X_s$ always follows the same functional form. Mechanisms which may be responsible for the observed variations in $R_s$ and $X_s$ are briefly discussed.Comment: 4 pages, 4 figure

New Insights into the Heterogeneity of the Tagish Lake Meteorite: Soluble Organic Compositions of Variously Altered Specimens

The Tagish Lake carbonaceous chondrite exhibits a unique compositional heterogeneity that may be attributed to varying degrees of aqueous alteration within the parent body asteroid. Previous analyses of soluble organic compounds from four Tagish Lake meteorite specimens (TL5b, TL11h, TL11i, TL11v) identified distinct distributions and isotopic compositions that appeared to be linked to their degree of parent body processing (Herd et al. 2011; Glavin et al. 2012; Hilts et al. 2014). In the present study, we build upon these initial observations and evaluate the molecular distribution of amino acids, aldehydes and ketones, monocarboxylic acids, and aliphatic and aromatic hydrocarbons, including compoundspecific 13C compositions, for three additional Tagish Lake specimens: TL1, TL4, and TL10a. TL1 contains relatively high abundances of soluble organics and appears to be a moderately altered specimen, similar to the previously analyzed TL5b and TL11h lithologies. In contrast, specimens TL4 and TL10a both contain relatively low abundances of all of the soluble organic compound classes measured, similar to TL11i and TL11v. The organicdepleted composition of TL4 appears to have resulted from a relatively low degree of parent body aqueous alteration. In the case of TL10a, some unusual properties (e.g., the lack of detection of intrinsic monocarboxylic acids and aliphatic and aromatic hydrocarbons) suggest that it has experienced extensive alteration and/or a distinct organicdepleted alteration history. Collectively, these varying compositions provide valuable new insights into the relationships between asteroidal aqueous alteration and the synthesis and preservation of soluble organic compounds

Content and Mechanism of Action of National Antimicrobial Stewardship Interventions on Management of Respiratory Tract Infections in Primary and Community Care

A major modifiable factor contributing to antimicrobial resistance (AMR) is inappropriate use and overuse of antimicrobials, such as antibiotics. This study aimed to describe the content and mechanism of action of antimicrobial stewardship (AMS) interventions to improve appropriate antibiotic use for respiratory tract infections (RTI) in primary and community care. This study also aimed to describe who these interventions were aimed at and the specific behaviors targeted for change. Evidence-based guidelines, peer-review publications, and infection experts were consulted to identify behaviors relevant to AMS for RTI in primary care and interventions to target these behaviors. Behavior change tools were used to describe the content of interventions. Theoretical frameworks were used to describe mechanisms of action. A total of 32 behaviors targeting six different groups were identified (patients; prescribers; community pharmacists; providers; commissioners; providers and commissioners). Thirty-nine interventions targeting the behaviors were identified (patients = 15, prescribers = 22, community pharmacy staff = 8, providers = 18, and commissioners = 18). Interventions targeted a mean of 5.8 behaviors (range 1–27). Influences on behavior most frequently targeted by interventions were psychological capability (knowledge and skills); reflective motivation (beliefs about consequences, intentions, social/professional role and identity); and physical opportunity (environmental context and resources). Interventions were most commonly characterized as achieving change by training, enabling, or educating and were delivered mainly through guidelines, service provision, and communications & marketing. Interventions included a mean of four Behavior Change Techniques (BCTs) (range 1–14). We identified little intervention content targeting automatic motivation and social opportunity influences on behavior. The majority of interventions focussed on education and training, which target knowledge and skills though the provision of instructions on how to perform a behavior and information about health consequences. Interventions could be refined with the inclusion of relevant BCTs, such as goal-setting and action planning (identified in only a few interventions), to translate instruction on how to perform a behavior into action. This study provides a platform to refine content and plan evaluation of antimicrobial stewardship interventions