Design, Synthesis, and Evaluation of Tetrasubstituted Pyridines as Potent 5-HT2C Receptor Agonists.

A series of pyrido[3,4-d]azepines that are potent and selective 5-HT2C receptor agonists is disclosed. Compound 7 (PF-04781340) is identified as a suitable lead owing to good 5-HT2C potency, selectivity over 5-HT2B agonism, and in vitro ADME properties commensurate with an orally available and CNS penetrant profile. The synthesis of a novel bicyclic tetrasubstituted pyridine core template is outlined, including rationale to account for the unexpected formation of aminopyridine 13 resulting from an ammonia cascade cyclization.We would like to thank the EPSRC (SVL, grant nº EP/K0099494/1 and nº EP/K039520/1) for financial support.This is the accepted manuscript. The final version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/ml500507v

Why do women invest in pre-pregnancy health and care? A qualitative investigation with women attending maternity services

Background Despite the importance attributed to good pre-pregnancy care and its potential to improve pregnancy and child health outcomes, relatively little is known about why women invest in pre-pregnancy health and care. We sought to gain insight into why women invested in pre-pregnancy health and care. Methods We carried out 20 qualitative in-depth interviews with pregnant or recently pregnant women who were drawn from a survey of antenatal clinic attendees in London, UK. Interviewees were purposively sampled to include high and low investors in pre-pregnancy health and care, with variation in age, partnership status, ethnicity and pre-existing medical conditions. Data analysis was conducted using the Framework method. Results We identified three groups in relation to pre-pregnancy health and care: 1) The “prepared” group, who had high levels of pregnancy planning and mostly positive attitudes to micronutrient supplementation outside of pregnancy, carried out pre-pregnancy activities such as taking folic acid and making changes to diet and lifestyle. 2) The “poor knowledge” group, who also had high levels of pregnancy planning, did not carry out pre-pregnancy activities and described themselves as having poor knowledge. Elsewhere in their interviews they expressed a strong dislike of micronutrient supplementation. 3) The “absent pre-pregnancy period” group, had the lowest levels of pregnancy planning and also expressed anti-supplement views. Even discussing the pre-pregnancy period with this group was difficult as responses to questions quickly shifted to focus on pregnancy itself. Knowledge of folic acid was poor in all groups. Conclusion Different pre-pregnancy care approaches are likely to be needed for each of the groups. Among the “prepared” group, who were proactive and receptive to health messages, greater availability of information and better response from health professionals could improve the range of pre-pregnancy activities carried out. Among the “poor knowledge” group, better response from health professionals might yield greater uptake of pre-pregnancy information. A different, general health strategy might be more appropriate for the “absent pre-pregnancy period” group. The fact that general attitudes to micronutrient supplementation were closely related to whether or not women invested in pre-pregnancy health and care was an unanticipated finding and warrants further investigation.This report is independent research commissioned and funded by the Department of Health Policy Research Programme Pre-Pregnancy Health and Care in England: Exploring Implementation and Public Health Impact, 006/0068

Measurement of the Spectral Shape of the beta-decay of 137Xe to the Ground State of 137Cs in EXO-200 and Comparison with Theory

We report on a comparison between the theoretically predicted and experimentally measured spectra of the first-forbidden non-unique $\beta$-decay transition ^{137}\textrm{Xe}(7/2^-)\to\,^{137}\textrm{Cs}(7/2^+). The experimental data were acquired by the EXO-200 experiment during a deployment of an AmBe neutron source. The ultra-low background environment of EXO-200, together with dedicated source deployment and analysis procedures, allowed for collection of a pure sample of the decays, with an estimated signal-to-background ratio of more than 99-to-1 in the energy range from 1075 to 4175 keV. In addition to providing a rare and accurate measurement of the first-forbidden non-unique $\beta$-decay shape, this work constitutes a novel test of the calculated electron spectral shapes in the context of the reactor antineutrino anomaly and spectral bump.Comment: Version as accepted by PR

Exploring the views of young women and their healthcare professionals on dietary habits and supplementation practices in adolescent pregnancy: a qualitative study

Background: Nutrition is a modifiable factor affecting foetal growth and pregnancy outcomes. Inadequate nutrition is of particular concern in adolescent pregnancies with poor quality diet and competing demands for nutrients. The aim of this study was to explore knowledge and understanding of nutrition advice during adolescent pregnancy,and identify barriers and facilitators to dietary change and supplementation use in this vulnerable population. Methods: Semi-structured interviews were conducted with young women and key antenatal healthcare providers: midwives, family nurses and obstetricians. Doncaster, Manchester and London were chosen as sites offering different models of midwifery care alongside referral to the Family Nurse Partnership programme. Results: A total of 34 young women (adolescents aged 16–19 years) and 20 health professionals were interviewed. Young women made small changes to their dietary intake despite limited knowledge and social constraints. Supplementation use varied; the tablet format was identified by few participants as a barrier but forgetting to take them was the main reason for poor adherence. Health professionals provided nutrition information but often lack the time and resources to tailor this appropriately. Young women’s prime motivator was a desire to have a healthy baby; they wanted to understand the benefits of supplementation and dietary change in those terms. Conclusion: Pregnancy is a window of opportunity for improving nutrition but often constrained by social circumstances. Health professionals should be supported in their role to access education, training and resources which build their self-efficacy to facilitate change in this vulnerable population group beyond the routine care they provide

A qualitative investigation of lived experiences of long-term health condition management with people who are food insecure.

Background: As more people are living with one or more chronic health conditions, supporting patients to become activated, self-managers of their conditions has become a key health policy focus both in the UK and internationally. There is also growing evidence in the UK that those with long term health conditions have an increased risk of being food insecure. While international evidence indicates that food insecurity adversely affects individual's health condition management capability, little is known about how those so affected manage their condition(s) in this context. An investigation of lived experience of health condition management was undertaken with food insecure people living in north east Scotland. The study aimed to explore the challenges facing food insecure people in terms of, i. their self-care condition management practices, and ii. disclosing and discussing the experience of managing their condition with a health care professional, and iii. Notions of the support they might wish to receive from them. Methods: Twenty in-depth interviews were conducted with individuals attending a food bank and food pantry in north east Scotland. Interview audio recordings were fully transcribed and thematically analysed. Results: Individuals reporting multiple physical and mental health conditions, took part in the study. Four main themes were identified i.e.: 1. food practices, trade-offs and compromises, that relate to economic constraints and lack of choice; 2. illness experiences and food as they relate to physical and mental ill-health; 3. (in) visibility of participants' economic vulnerability within health care consultations; and 4. perceptions and expectations of the health care system. Conclusions: This study, the first of its kind in the UK, indicated that participants' health condition management aspirations were undermined by the experience of food insecurity, and that their health care consultations in were, on the whole, devoid of discussions of those challenges. As such, the study indicated practical and ethical implications for health care policy, practice and research associated with the risk of intervention-generated health inequalities that were suggested by this study. Better understanding is needed about the impact of household food insecurity on existing ill health, wellbeing and health care use across the UK

Generative Adversarial Networks for Scintillation Signal Simulation in EXO-200

Generative Adversarial Networks trained on samples of simulated or actual events have been proposed as a way of generating large simulated datasets at a reduced computational cost. In this work, a novel approach to perform the simulation of photodetector signals from the time projection chamber of the EXO-200 experiment is demonstrated. The method is based on a Wasserstein Generative Adversarial Network - a deep learning technique allowing for implicit non-parametric estimation of the population distribution for a given set of objects. Our network is trained on real calibration data using raw scintillation waveforms as input. We find that it is able to produce high-quality simulated waveforms an order of magnitude faster than the traditional simulation approach and, importantly, generalize from the training sample and discern salient high-level features of the data. In particular, the network correctly deduces position dependency of scintillation light response in the detector and correctly recognizes dead photodetector channels. The network output is then integrated into the EXO-200 analysis framework to show that the standard EXO-200 reconstruction routine processes the simulated waveforms to produce energy distributions comparable to that of real waveforms. Finally, the remaining discrepancies and potential ways to improve the approach further are highlighted.Comment: 20 pages, 10 figure