Stability of Scalar Fields in Warped Extra Dimensions

This work sets up a general theoretical framework to study stability of models with a warped extra dimension where N scalar fields couple minimally to gravity. Our analysis encompasses Randall-Sundrum models with branes and bulk scalars, and general domain-wall models. We derive the Schrodinger equation governing the spin-0 spectrum of perturbations of such a system. This result is specialized to potentials generated using fake supergravity, and we show that models without branes are free of tachyonic modes. Turning to the existence of zero modes, we prove a criterion which relates the number of normalizable zero modes to the parities of the scalar fields. Constructions with definite parity and only odd scalars are shown to be free of zero modes and are hence perturbatively stable. We give two explicit examples of domain-wall models with a soft wall, one which admits a zero mode and one which does not. The latter is an example of a model that stabilizes a compact extra dimension using only bulk scalars and does not require dynamical branes.Comment: 25 pages, 2 figures; v2: minor changes to text, references added, matches published versio

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

Multiple triangulation and collaborative research using qualitative methods to explore decision making in pre-hospital emergency care.

BACKGROUND: Paramedics make important and increasingly complex decisions at scene about patient care. Patient safety implications of influences on decision making in the pre-hospital setting were previously under-researched. Cutting edge perspectives advocate exploring the whole system rather than individual influences on patient safety. Ethnography (the study of people and cultures) has been acknowledged as a suitable method for identifying health care issues as they occur within the natural context. In this paper we compare multiple methods used in a multi-site, qualitative study that aimed to identify system influences on decision making. METHODS: The study was conducted in three NHS Ambulance Trusts in England and involved researchers from each Trust working alongside academic researchers. Exploratory interviews with key informants e.g. managers (n = 16) and document review provided contextual information. Between October 2012 and July 2013 researchers observed 34 paramedic shifts and ten paramedics provided additional accounts via audio-recorded 'digital diaries' (155 events). Three staff focus groups (total n = 21) and three service user focus groups (total n = 23) explored a range of experiences and perceptions. Data collection and analysis was carried out by academic and ambulance service researchers as well as service users. Workshops were held at each site to elicit feedback on the findings and facilitate prioritisation of issues identified. RESULTS: The use of a multi-method qualitative approach allowed cross-validation of important issues for ambulance service staff and service users. A key factor in successful implementation of the study was establishing good working relationships with academic and ambulance service teams. Enrolling at least one research lead at each site facilitated the recruitment process as well as study progress. Active involvement with the study allowed ambulance service researchers and service users to gain a better understanding of the research process. Feedback workshops allowed stakeholders to discuss and prioritise findings as well as identify new research areas. CONCLUSION: Combining multiple qualitative methods with a collaborative research approach can facilitate exploration of system influences on patient safety in under-researched settings. The paper highlights empirical issues, strengths and limitations for this approach. Feedback workshops were effective for verifying findings and prioritising areas for future intervention and research

Improved measurement of the K+->pi+nu(nu)over-bar branching ratio

An additional event near the upper kinematic limit for K+-->pi(+)nu(nu) over bar has been observed by experiment E949 at Brookhaven National Laboratory. Combining previously reported and new data, the branching ratio is B(K+-->pi(+)nu(nu) over bar)=(1.47(-0.89)(+1.30))x10(-10) based on three events observed in the pion momentum region 211<P<229 MeV/c. At the measured central value of the branching ratio, the additional event had a signal-to-background ratio of 0.9

Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

A process for risk-focused maintenance

This report presents a process for focusing maintenance resources on components that enable nuclear plant systems to perform their essential functions and on components whose failure may initiate challenges to safety systems, so as to have the greatest impact in decreasing risk. The process provides criteria, based on risk, for deciding which components are critical to risk and determining what maintenance activities are required to ensure reliable operation of those risk-critical components. Two approaches are provided for selection of risk-critical components. One approach uses the results of a Probabilistic Risk Assessment (PRA); the other is based on the methodology developed for this report, which has a basis in PRA although it does not use the results of a PRA study. Following identification of risk-critical components, both approaches use a single methodology for determining what maintenance activities are required to ensure reliable operation of the identified components. The report also provides demonstrations of application of the two approaches to selection of risk-critical components and demonstrations of application of the methodology for determining what maintenance activities are required to an active standby safety system, a normally operating system, and passive components. 5 refs., 11 figs., 1 tab

Modelling terrigenous DOC across the north west European Shelf: Fate of riverine input and impact on air-sea CO2 fluxes

Terrigenous carbon in aquatic systems is increasingly recognised as an important part of the global carbon cycle. Despite this, the fate and distribution of terrigenous dissolved organic carbon (tDOC) in coastal and oceanic systems is poorly understood. We have implemented a theoretical framework for the degradation of tDOC across the land to ocean continuum in a 3D hydrodynamical-biogeochemical model on the North West European Shelf. A key feature of this model is that both photochemical and bacterial tDOC degradation rates are age dependant constituting an advance in our ability to describe carbon cycling in the marine environment. Over the time period 1986-2015, 182±17 Gmol yr− 1 of riverine tDOC is input to the shelf. Results indicate that bacterial degradation is by far the most important process in removing tDOC on the shelf, contributing to 73±6 % (132±11 Gmol yr− 1 ) of the total removal flux, while 21±3 % (39±6 Gmol yr− 1 ) of riverine tDOC was advected away from the shelf and photochemical degradation removing 5±0.5 % of the riverine flux. Explicitly including tDOC in the model decreased the air-sea carbon dioxide (CO2) flux by 112±8 Gmol yr− 1 (4±0.4 %), an amount approximately equivalent to the CO2 released by the UK chemical industry in 2020. The reduction is equivalent to 62 % of the riverine tDOC input to the shelf while approximately 17 % of riverine input is incorporated into the foodweb. This work can improve the assumptions of the fate of tDOC by Earth System Models and demonstrates that the inclusion of tDOC in models can impact ecosystem dynamics and change predicted global carbon budgets for the ocean

Assessment of Objectively Measured Physical Activity Levels in Individuals with Intellectual Disabilities with and without Down's Syndrome

Objective: To investigate, using accelerometers, the levels of physical activity being undertaken by individuals with intellectual disabilities with and without Down’s syndrome. Methods: One hundred and fifty two individuals with intellectual disabilities aged 12–70 years from East and South-East England. Physical activity levels in counts per minute (counts/min), steps per day (steps/day), and minutes of sedentary, light, moderate, vigorous, and moderate to vigorous physical activity (MVPA) measured with a uni-axial accelerometer (Actigraph GT1M) for seven days. Results: No individuals with intellectual disabilities met current physical activity recommendations. Males were more active than females. There was a trend for physical activity to decline and sedentary behaviour to increase with age, and for those with more severe levels of intellectual disability to be more sedentary and less physically active, however any relationship was not significant when adjusted for confounding variables. Participants with Down’s syndrome engaged in significantly less physical activity than those with intellectual disabilities without Down’s syndrome and levels of activity declined significantly with age. Conclusions: Individuals with intellectual disabilities, especially those with Down’s syndrome may be at risk of developing diseases associated with physical inactivity. There is a need for well-designed, accessible, preventive health promotio

The interaction between a sexually transferred steroid hormone and a female protein regulates oogenesis in the malaria mosquito anopheles gambiae

Molecular interactions between male and female factors during mating profoundly affect the reproductive behavior and physiology of female insects. In natural populations of the malaria mosquito Anopheles gambiae, blood-fed females direct nutritional resources towards oogenesis only when inseminated. Here we show that the mating-dependent pathway of egg development in these mosquitoes is regulated by the interaction between the steroid hormone 20-hydroxy-ecdysone (20E) transferred by males during copulation and a female Mating-Induced Stimulator of Oogenesis (MISO) protein. RNAi silencing of MISO abolishes the increase in oogenesis caused by mating in blood-fed females, causes a delay in oocyte development, and impairs the function of male-transferred 20E. Co-immunoprecipitation experiments show that MISO and 20E interact in the female reproductive tract. Moreover MISO expression after mating is induced by 20E via the Ecdysone Receptor, demonstrating a close cooperation between the two factors. Male-transferred 20E therefore acts as a mating signal that females translate into an increased investment in egg development via a MISO-dependent pathway. The identification of this male–female reproductive interaction offers novel opportunities for the control of mosquito populations that transmit malaria

Narratives for drug design

We explore the role of narratives of complex systems in anti-cancer drug design. We set out the value of narratives relating to cancer in promoting awareness of risky behaviour and in supporting decision-making regarding treatment options. We present cancer as a dysregulated, complex system that has emergent behaviours at multiple scales, and is governed by dynamical spatio-temporal processes. We show that this system changes structure and function in response to anti-cancer drugs, and explain that these changes are sufficiently complex to impede effective drug design. We pose what narrative might offer to support the process of drug design, providing an example of work done to date that might serve as a foundation for narrating complexity. We suggest ways of using this work combined with that of others to begin to consider narrating drug design