SEX DIFFERENCES IN THE NEURAL CIRCUITS THAT PREDICT ALCOHOL DEPENDENCE

Although neurobiological mechanisms underlying alcohol use and dependence have been extensively researched, mechanisms explaining sex differences in alcohol drinking are poorly understood. The cortical-striatal circuit plays a key role in the development of alcohol dependence, and it has previously been shown that oscillations from these regions predict drinking in non-dependent male rats, but not in female rats. Since women are more likely to report using alcohol for negative reinforcement reasons and are more sensitive to stress-induced relapse, we hypothesized that stress-related neural circuits may contain more information predictive of female drinking. To test this, we determined whether cortical, striatal, and/or limbic oscillations during alcohol self-administration would distinguish between dependent and non-dependent rats in a sex-specific manner. Male and female Sprague-Dawley rats were trained to self-administer 10% alcohol before implanting bilateral electrodes targeting the infralimbic medial prefrontal cortex (mPFC), nucleus accumbens shell (NAcSh), and central nucleus of the amygdala (CeA). Then, half of the rats were exposed to four weeks of chronic intermittent alcohol (CIA) vapor (14 hours on/10 hours off) to induce dependence. After dependence was established and during acute withdrawal (approximately 7 hours after the vapor turns off), local field potentials (LFPs) were recorded from the mPFC, NAcSh, and CeA during another round of self-administration sessions. Using an unbiased machine learning approach, we built predictive models to determine whether oscillations could distinguish CIA-exposed from control rats in both sexes. Overall, female rats self-administered more alcohol than males. CIA exposure increased alcohol self-administration in both sexes, but to a larger extent in males. Preliminary analysis revealed that NAcSh and mPFC LFPs best predict CIA exposure in males, while CeA and mPFC oscillations best predict CIA exposure in females. These data provide support for sex-specific neurobiological correlates of dependence, which contributes to our understanding of sex differences in alcohol misuse

Intravenous remifentanil patient-controlled analgesia versus intramuscular pethidine for pain relief in labour (RESPITE): an open-label, multicentre, randomised controlled trial

Background: Approximately a third of women receiving pethidine for labour pain subsequently require an epidural, which provides effective pain relief but increases the risk of instrumental delivery. Remifentanil patient controlled analgesia (PCA) in labour is an alternative to pethidine, but not widely utilized. We sought to determine epidural rates amongst women using remifentanil PCA compared to pethidine.Methods: We conducted a randomised, parallel, open-label trial in 14 UK maternity units. Women at term gestation, in labour with a singleton cephalic presentation, requesting opioid pain relief, were randomly assigned (1:1) to remifentanil PCA (40μg bolus with a two minute “lock-out”) or intramuscular pethidine (100mg, four-hourly, up to 400mg). Web-based or telephone randomisation minimised allocations by parity, age, ethnicity and mode of labour onset. The primary outcome was the proportion of women who received epidural analgesia after enrolment. To detect a reduction in epidural conversion from 30% to 15% with 90% power, with a 15% anticipated attrition from urgent delivery by emergency caesarean section, required 400 women. Primary analyses were unadjusted and by intention-to-treat. ISRCTN29654603.Findings: Between May 13, 2014, and Sept 2, 2016, 201 women were randomly assigned to the remifentanil PCA group and 200 to the pethidine group. One participant in the pethidine group withdrew consent, leaving 199 for analyses. The proportions of epidural conversion were 19% (39 of 201) in the remifentanil PCA group and 41% (81 of 199) in the pethidine group (risk ratio 0·48, 95% CI 0·34–0·66; p less 0·0001). There were no serious adverse events or drug reactions directly attributable to either analgesic during the study.Interpretation: Intravenous remifentanil PCA halved the proportion of epidural conversions compared with intramuscular pethidine. This finding challenges routine pethidine use as standard of care in labour

Reel-to-reel atmospheric pressure dielectric barrier discharge (DBD) plasma treatment of polypropylene films

© 2017 by the authors. Atmospheric pressure plasma treatment of the surface of a polypropylene film can significantly increase its surface energy and, thereby improve the printability of the film. A laboratory-scale dielectric barrier discharge (DBD) system has therefore been developed, which simulates the electrode configuration and reel-to-reel web transport mechanism used in a typical industrial-scale system. By treating the polypropylene in a nitrogen discharge, we have shown that the water contact angle could be reduced by as much as 40° compared to the untreated film, corresponding to an increase in surface energy of 14 mNm-1. Ink pull-off tests showed that the DBD plasma treatment resulted in excellent adhesion of solvent-based inks to the polypropylene film

Identification of depression in women during pregnancy and the early postnatal period using the Whooley questions and the Edinburgh Postnatal Depression Scale : protocol for the Born and Bred in Yorkshire: PeriNatal Depression Diagnostic Accuracy (BaBY PaNDA) study

INTRODUCTION: Perinatal depression is well recognised as a mental health condition but <50% of cases are identified by healthcare professionals in routine clinical practice. The Edinburgh Postnatal Depression Scale (EPDS) is often used to detect symptoms of postnatal depression in maternity and child services. The National Institute for Health and Care Excellence (NICE) recommends 2 'ultra-brief' case-finding questions (the Whooley questions) to aid identification of depression during the perinatal period, but this recommendation was made in the absence of any validation studies in a perinatal population. Limited research exists on the acceptability of these depression case-finding instruments and the cost-effectiveness of routine screening for perinatal depression. METHODS AND ANALYSIS: The diagnostic accuracy of the Whooley questions and the EPDS will be determined against a reference standard (the Client Interview Schedule-Revised) during pregnancy (around 20 weeks) and the early postnatal period (around 3-4 months post partum) in a sample of 379 women. Further outcome measures will assess a range of psychological comorbidities, health-related quality of life and resource utilisation. Women will be followed up 12 months postnatally. The sensitivity, specificity and predictive values of the Whooley questions and the EPDS will be calculated against the reference standard at 20 weeks pregnancy and 3-4 months post partum. Acceptability of the depression case-finding instruments to women and healthcare professionals will involve in-depth qualitative interviews. An existing decision analytic model will be adapted to determine the cost-effectiveness of routine screening for perinatal depression. ETHICS AND DISSEMINATION: This study is considered low risk for participants. Robust protocols will deal with cases where risk of depression, self-harm or suicide is identified. The protocol received favourable ethical opinion from the North East-York Research Ethics Committee (reference: 11/NE/0022). The study findings will be published in peer-reviewed journals and presented at relevant conferences

Justifications-on-demand as a device to promote shifts of attention associated with relational thinking in elementary arithmetic

Student responses to arithmetical questions that can be solved by using arithmetical structure can serve to reveal the extent and nature of relational, as opposed to computational thinking. Here, student responses to probes which require them to justify-on-demand are analysed using a conceptual framework which highlights distinctions between different forms of attention. We analyse a number of actions observed in students in terms of forms of attention and shifts between them: in the short-term (in the moment), medium-term (over several tasks), and long-term (over a year). The main factors conditioning students´ attention and its movement are identified and some didactical consequences are proposed

You’ll never walk alone: supportive social relations in a football and mental health project

Football can bring people together in acts of solidarity and togetherness. This spirit is most evocatively illustrated in the world renowned football anthem You’ll Never Walk Alone (YNWA). In this paper we argue that this spirit can be effectively harnessed in nursing and mental health care. We draw on data from qualitative interviews undertaken as part of evaluating a football and mental health project to explore the nature of supportive social relations therein. We use some of the lyrics from YNWA as metaphor to frame our thematic analysis. We are especially interested in the interactions between the group facilitators and group members, but also address aspects of peer support within the groups. A contrast is drawn between the flexible interpersonal boundaries and self-disclosure evident in the football initiative and the reported more distant relations with practitioners in mainstream mental health services. Findings suggest scope for utilising more collective, solidarity enhancing initiatives and attention to alliances and boundaries to maximise engagement and therapeutic benefits within routine practice

Proof of the Hyperplane Zeros Conjecture of Lagarias and Wang

We prove that a real analytic subset of a torus group that is contained in its image under an expanding endomorphism is a finite union of translates of closed subgroups. This confirms the hyperplane zeros conjecture of Lagarias and Wang for real analytic varieties. Our proof uses real analytic geometry, topological dynamics and Fourier analysis.Comment: 25 page

Diversity and distribution of genetic variation in gammarids: Comparing patterns between invasive and non-invasive species

© 2017 Published by John Wiley & Sons Ltd. Biological invasions are worldwide phenomena that have reached alarming levels among aquatic species. There are key challenges to understand the factors behind invasion propensity of non-native populations in invasion biology. Interestingly, interpretations cannot be expanded to higher taxonomic levels due to the fact that in the same genus, there are species that are notorious invaders and those that never spread outside their native range. Such variation in invasion propensity offers the possibility to explore, at fine-scale taxonomic level, the existence of specific characteristics that might predict the variability in invasion success. In this work, we explored this possibility from a molecular perspective. The objective was to provide a better understanding of the genetic diversity distribution in the native range of species that exhibit contrasting invasive propensities. For this purpose, we used a total of 784 sequences of the cytochrome c oxidase subunit I of mitochondrial DNA (mtDNA-COI) collected from seven Gammaroidea, a superfamily of Amphipoda that includes species that are both successful invaders (Gammarus tigrinus, Pontogammarus maeoticus, and Obesogammarus crassus) and strictly restricted to their native regions (Gammarus locusta, Gammarus salinus, Gammarus zaddachi, and Gammarus oceanicus). Despite that genetic diversity did not differ between invasive and non-invasive species, we observed that populations of non-invasive species showed a higher degree of genetic differentiation. Furthermore, we found that both geographic and evolutionary distances might explain genetic differentiation in both non-native and native ranges. This suggests that the lack of population genetic structure may facilitate the distribution of mutations that despite arising in the native range may be beneficial in invasive ranges. The fact that evolutionary distances explained genetic differentiation more often than geographic distances points toward that deep lineage divergence holds an important role in the distribution of neutral genetic diversity

Controlled in vitro delivery of voriconazole and diclofenac to the cornea using contact lenses for the treatment of Acanthamoeba keratitis

Acanthamoeba keratitis is caused by a protozoal infection of the cornea, with 80% of cases involving the improper use of contact lenses. The infection causes intense pain and is potentially blinding. However, early diagnosis improves treatment efficacy and the chances of healing. Despite the apparent accessibility of the cornea, patients do not always respond well to current eye drop treatments largely due to rapid dose loss due to blinking and nasolacrimal drainage. Here, the topical drug delivery of voriconazole alone and in combination with diclofenac via drug-loaded contact lenses, were investigated in vitro. The contact lenses were applied onto excised porcine eyeballs and maintained at 32°C under constant irrigation, with simulated tear fluid applied to mimic in vivo conditions. The drug delivered to the corneas was quantified by HPLC analysis. The system was further tested in terms of cytotoxicity and a scratch wound repopulation model, using corneal epithelial cells. Sustained drug delivery to the cornea was achieved and for voriconazole, the MIC against Acanthamoeba castellanii was attained alone and in combination with diclofenac. MTT and scratch wound data showed reasonable cell proliferation and wound repopulation at the drug doses used, supporting further development of the system to treat Acanthamoeba keratitis