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

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

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

Flexible aggregation in multiple attribute decision making: Application to the Kuranda Range Road Upgrade

The conventional method of aggregating the satisfaction of transport projects with respect to multiple attributes is commonly some variant of Simple Additive Weighting (SAW), which involves the sum of products of standardized outcomes of projects with respect to attributes and attribute importance weights. It is suggested that alternative forms of aggregation might be more useful, in particular, the Ordered Weighted Averaging (OWA) operator introduced by Yager (1988). Attribute importance weights and satisfaction of attributes by projects may be aggregated prior to aggregation via an OWA operator. In this case OWA operator weights may be based on the "attitudinal character of the decision maker expressed in terms of the degree of "orness and "andness of the aggregation. A well-known approach is maximum entropy aggregation, in which weights are derived to be as "even (or as minimally dispersed) as a possible subject to satisfying a given "orness or "andness constraint. Recently, aggregation processes have been proposed by Larsen (199920022003) which have several desirable properties and also may be considered as alternative forms of aggregation. An example is given relating to the Kuranda Range Road upgrade (Queensland, Australia) which is limited by grade, poor overtaking opportunities, poor horizontal alignment, and other constraints, and the road is expected to become increasingly congested over the next few years. A more flexible Multiple Attribute Decision Making is used to identify a "best project from a set of four alternative projects

Materials and Textile Architecture Analyses for Mechanical Counter-Pressure Space Suits using Active Materials

Mechanical counter-pressure (MCP) space suits have the potential to improve the mobility of astronauts as they conduct planetary exploration activities. MCP suits differ from traditional gas-pressurized space suits by applying surface pressure to the wearer using tight-fitting materials rather than pressurized gas, and represent a fundamental change in space suit design. However, the underlying technologies required to provide uniform compression in a MCP garment at sufficient pressures for space exploration have not yet been perfected, and donning and doffing a MCP suit remains a significant challenge. This research effort focuses on the novel use of active material technologies to produce a garment with controllable compression capabilities (up to 30 kPa) to address these problems. We provide a comparative study of active materials and textile architectures for MCP applications; concept active material compression textiles to be developed and tested based on these analyses; and preliminary biaxial braid compression garment modeling results.United States. National Aeronautics and Space Administration (OCT Space Technology Research Fellowship Grant NNX11AM62H)MIT-Portugal Progra

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