Showing papers by "Keele University published in 2011"

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Abstract: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Using mapping studies as the basis for further research - A participant-observer case study

Abstract: Context: We are strong advocates of evidence-based software engineering (EBSE) in general and systematic literature reviews (SLRs) in particular. We believe it is essential that the SLR methodology is used constructively to support software engineering research. Objective: This study aims to assess the value of mapping studies which are a form of SLR that aims to identify and categorise the available research on a broad software engineering topic. Method: We used a multi-case, participant-observer case study using five examples of studies that were based on preceding mapping studies. We also validated our results by contacting two other researchers who had undertaken studies based on preceding mapping studies and by assessing review comments related to our follow-on studies. Results: Our original case study identified 11 unique benefits that can accrue from basing research on a preceding mapping study of which only two were case specific. We also identified nine problems associated with using preceding mapping studies of which two were case specific. These results were consistent with the information obtained from the validation activities. We did not find an example of an independent research group making use of a mapping study produced by other researchers. Conclusion: Mapping studies can save time and effort for researchers and provide baselines to assist new research efforts. However, they must be of high quality in terms of completeness and rigour if they are to be a reliable basis for follow-on research.

Homogeneous studies of transiting extrasolar planets – IV. Thirty systems with space-based light curves

Abstract: I calculate the physical properties of 32 transiting extrasolar planet and brown-dwarf systems from existing photometric observations and measured spectroscopic parameters. The systems studied include fifteen observed by the CoRoT satellite, ten by Kepler and five by the Deep Impact spacecraft. Inclusion of the objects studied in previous papers leads to a sample of 58 transiting systems with homogeneously measured properties. The Kepler data include observations from Quarter 2, and my analyses of several of the systems are the first to be based on short-cadence data from this satellite. The light curves are modelled using the JKTEBOP code, with attention paid to the treatment of limb darkening, contaminating light, orbital eccentricity, correlated noise, and numerical integration over long exposure times. The physical properties are derived from the light curve parameters, spectroscopic characteristics of the host star, and constraints from five sets of theoretical stellar model predictions. An alternative approach using a calibration from eclipsing binary star systems is explored and found to give comparable results whilst imposing a much smaller computational burden. My results are in good agreement with published properties for most of the transiting systems, but discrepancies are identified for CoRoT-5, CoRoT-8, CoRoT-13, Kepler-5 and Kepler-7. Many of the errorbars quoted in the literature are underestimated. Refined orbital ephemerides are given for CoRoT-8 and for the Kepler planets. Asteroseismic constraints on the density of the host stars are in good agreement with the photometric equivalents for HD17156 and TrES-2, but not for HAT-P-7 and HAT-P-11. Complete error budgets are generated for each transiting system, allowing identification of the observations best-suited to improve measurements of their physical properties. Whilst most systems would benefit from further photometry and spectroscopy, HD17156, HD80606, HAT-P-7 and TrES-2 are now extremely well characterised. HAT-P-11 is an exceptional candidate for studying starspots. The orbital ephemerides of some transiting systems are becoming uncertain and they should be re-observed in the near future. The primary results from the current work and from previous papers in the series have been placed in an online catalogue, from where they can be obtained in a range of formats for reference and further study. TEPCat is available at http://www.astro.keele.ac.uk/ jkt/tepcat/

Herschel Detects a Massive Dust Reservoir in Supernova 1987A

Abstract: We report far-infrared and submillimeter observations of supernova 1987A, the star whose explosion was observed on 23 February 1987 in the Large Magellanic Cloud, a galaxy located 160,000 light years away. The observations reveal the presence of a population of cold dust grains radiating with a temperature of about 17 to 23 kelvin at a rate of about 220 times the luminosity of the Sun. The intensity and spectral energy distribution of the emission suggest a dust mass of about 0.4 to 0.7 times the mass of the Sun. The radiation must originate from the supernova ejecta and requires the efficient precipitation of all refractory material into dust. Our observations imply that supernovae can produce the large dust masses detected in young galaxies at very high redshifts.

Superabsorbent hydrogel composites and nanocomposites: A review

Abstract: Superabsorbent polymers are hydrophilic networks that can absorb and retain huge amounts of water or aqueous solutions. They are currently used in many areas including hygienic and bio-related uses (particularly in disposable diapers), agricultural uses (e.g., water reserving in soil, soil conditioning, and controlled release of agrochemicals), pharmaceutical dosage forms, separation technology, fibers/textiles, water-swelling rubbers, soft actuators/valves, electrical, construction, packaging, artificial snow, sludge/coal dewatering, fire-extinguishing gels, etc. Addition of clays and organo-modified clays into superabsorbent formulation has funded new generations of these hydrogels, i.e., superabsorbent hydrogel composites (SHCs) and superabsorbent hydrogel nanocomposites (SHNCs). New superabsorbent hydrogels are cheaper in price, and possess superior mechanical properties than non-composite counterparts. This review introduces the SHC and SHNC polymers with the focus on different minerals and humic additives, synthetic methods, the hydrogel characteristics and their applications. POLYM. COMPOS., 2011. © 2010 Society of Plastics Engineers

A high C/O ratio and weak thermal inversion in the atmosphere of exoplanet WASP-12b

Abstract: The transiting 'hot Jupiter' WASP-12b orbits a star slightly hotter than the Sun in a circular orbit at a distance of only 0023 astronomical units (AU), making it one of the hottest exoplanets known An analysis of dayside multi-wavelength photometry of WASP-12b reveals a carbon-rich atmosphere abundant in carbon monoxide Compared with model predictions, the atmosphere is depleted in water vapour and enhanced in methane content by two orders of magnitude In addition, the absence of a strong thermal inversion or a prominent stratosphere challenges existing theories about the atmospheres of such exoplanets A primordial carbon-to-oxygen ratio (C/O) greater than 08 in an exoplanet causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmospheres also can differ from those in the Solar System The solar C/O is 054 This study reports an analysis of spectra from the transiting hot Jupiter WASP-12b that reveals that C/O>1 in its atmosphere, based upon the observed concentrations of the prominent molecules CO, CH4 and H2O The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution A primordial C/O greater than 08 causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth1; the atmosphere can also differ from those in the Solar System1,2 The solar C/O is 054 (ref 3) Here we report an analysis of dayside multi-wavelength photometry4,5 of the transiting hot-Jupiter WASP-12b (ref 6) that reveals C/O ≥ 1 in its atmosphere The atmosphere is abundant in CO It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures We also find that the extremely irradiated atmosphere (T > 2,500 K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day–night energy circulation The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres7,8,9

Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination

Abstract: Progressive telomere shortening from cell division (replicative aging) provides a barrier for human tumor progression. This program is not conserved in laboratory mice, which have longer telomeres and constitutive telomerase. Wild species that do / do not use replicative aging have been reported, but the evolution of different phenotypes and a conceptual framework for understanding their uses of telomeres is lacking. We examined telomeres / telomerase in cultured cells from > 60 mammalian species to place different uses of telomeres in a broad mammalian context. Phylogeny-based statistical analysis reconstructed ancestral states. Our analysis suggested that the ancestral mammalian phenotype included short telomeres (< 20 kb, as we now see in humans) and repressed telomerase. We argue that the repressed telomerase was a response to a higher mutation load brought on by the evolution of homeothermy. With telomerase repressed, we then see the evolution of replicative aging. Telomere length inversely correlated with lifespan, while telomerase expression co-evolved with body size. Multiple independent times smaller, shorter-lived species changed to having longer telomeres and expressing telomerase. Trade-offs involving reducing the energetic / cellular costs of specific oxidative protection mechanisms (needed to protect < 20 kb telomeres in the absence of telomerase) could explain this abandonment of replicative aging. These observations provide a conceptual framework for understanding different uses of telomeres in mammals, support a role for human-like telomeres in allowing longer lifespans to evolve, demonstrate the need to include telomere length in the analysis of comparative studies of oxidative protection in the biology of aging, and identify which mammals can be used as appropriate model organisms for the study of the role of telomeres in human cancer and aging.

Heavy Metal Poisoning and Cardiovascular Disease

Abstract: Cardiovascular disease (CVD) is an increasing world health problem. Traditional risk factors fail to account for all deaths from CVD. It is mainly the environmental, dietary and lifestyle behavioral factors that are the control keys in the progress of this disease. The potential association between chronic heavy metal exposure, like arsenic, lead, cadmium, mercury, and CVD has been less well defined. The mechanism through which heavy metals act to increase cardiovascular risk factors may act still remains unknown, although impaired antioxidants metabolism and oxidative stress may play a role. However, the exact mechanism of CVD induced by heavy metals deserves further investigation either through animal experiments or through molecular and cellular studies. Furthermore, large-scale prospective studies with follow up on general populations using appropriate biomarkers and cardiovascular endpoints might be recommended to identify the factors that predispose to heavy metals toxicity in CVD. In this review, we will give a brief summary of heavy metals homeostasis, followed by a description of the available evidence for their link with CVD and the proposed mechanisms of action by which their toxic effects might be explained. Finally, suspected interactions between genetic, nutritional and environmental factors are discussed.

The Kepler characterization of the variability among A- and F-type stars I. General overview

Abstract: Context. The Kepler spacecraft is providing time series of photometric data with micromagnitude precision for hundreds of A-F type stars. Aims. We present a first general characterization of the pulsational behaviour of A-F type stars as observed in the Kepler light curves of a sample of 750 candidate A-F type stars, and observationally investigate the relation between γ Doradus (γ Dor), δ Scuti (δ Sct), and hybrid stars. Methods. We compile a database of physical parameters for the sample stars from the literature and new ground-based observations. We analyse the Kepler light curve of each star and extract the pulsational frequencies using different frequency analysis methods. We construct two new observables, “energy ”a nd “efficiency”, related to the driving energy of the pulsation mode and the convective efficiency of the outer convective zone, respectively. Results. We propose three main groups to describe the observed variety in pulsating A-F type stars: γ Dor, δ Sct, and hybrid stars. We assign 63% of our sample to one of the three groups, and identify the remaining part as rotationally modulated/active stars, binaries, stars of different spectral type, or stars that show no clear periodic variability. 23% of the stars (171 stars) are hybrid stars, which is a much higher fraction than what has been observed before. We characterize for the first time a large number of A-F type stars (475 stars) in terms of number of detected frequencies, frequency range, and typical pulsation amplitudes. The majority of hybrid stars show frequencies with all kinds of periodicities within the γ Dor and δ Sct range, also between 5 and 10 d −1 , which is a challenge for the current models. We find indications for the existence of δ Sct and γ Dor stars beyond the edges of the current observational instability strips. The hybrid stars occupy the entire region within the δ Sct and γ Dor instability strips and beyond. Non-variable stars seem to exist within the instability strips. The location of γ Dor and δ Sct classes in the (Teff ,l ogg)-diagram has been extended. We investigate two newly constructed variables, “efficiency ”a nd “energy”, as a means to explore the relation between γ Dor and δ Sct stars. Conclusions. Our results suggest a revision of the current observational instability strips of δ Sct and γ Dor stars and imply an investigation of pulsation mechanisms to supplement the κ mechanism and convective blocking effect to drive hybrid pulsations. Accurate physical parameters for all stars are needed to confirm these findings.

Mortality and morbidity in Cushing's disease over 50 years in Stoke-on-Trent, UK: audit and meta-analysis of literature.

Abstract: Mortality in Cushing's disease is double that of the general population, but for patients in remission mortality to date is not increased.

A systematic review and synthesis of the quantitative and qualitative evidence behind patient-centred goal setting in stroke rehabilitation

Abstract: Objective: To map out from the literature the nature, extent and effects of application of patient-centred goal setting in stroke rehabilitation practice.Design: Systematic review.Data sources: A search was conducted in the Cochrane (Wiley), AMED, Medline (EBSCO), Embase, Sports discuss, Medline (Ovid) and CINAHL databases. Secondary search based on references from the preliminary search was undertaken.Review methods: Quantitative and qualitative studies that included aspects of patient-centredness and goal setting in stroke patients from 1980 to June 2010 were collected. Studies were scrutinized for relevance and quality based on published methodology. The findings were synthesized by aggregating the themes from the qualitative studies and relating them to relevant findings from the quantitative studies.Results: Eighteen qualitative and eight quantitative and one mixed method study conducted in stroke rehabilitation services ranging from acute to community rehabilitation were included. Themes that emerge...

Progress in SIFT-MS: breath analysis and other applications.

Abstract: The development of selected ion flow tube mass spectrometry, SIFT-MS, is described from its inception as the modified very large SIFT instruments used to demonstrate the feasibility of SIFT-MS as an analytical technique, towards the smaller but bulky transportable instruments and finally to the current smallest Profile 3 instruments that have been located in various places, including hospitals and schools to obtain on-line breath analyses. The essential physics and engineering principles are discussed, which must be appreciated to design and construct a SIFT-MS instrument. The versatility and sensitivity of the Profile 3 instrument is illustrated by typical mass spectra obtained using the three precursor ions H(3)O(+), NO(+) and O(2)(+)·, and the need to account for differential ionic diffusion and mass discrimination in the analytical algorithms is emphasized to obtain accurate trace gas analyses. The performance of the Profile 3 instrument is illustrated by the results of several pilot studies, including (i) on-line real time quantification of several breath metabolites for cohorts of healthy adults and children, which have provided representative concentration/population distributions, and the comparative analyses of breath exhaled via the mouth and nose that identify systemic and orally-generated compounds, (ii) the enhancement of breath metabolites by drug ingestion, (iii) the identification of HCN as a marker of Pseudomonas colonization of the airways and (iv) emission of volatile compounds from urine, especially ketone bodies, and from skin. Some very recent developments are discussed, including the quantification of carbon dioxide in breath and the combination of SIFT-MS with GC and ATD, and their significance. Finally, prospects for future SIFT-MS developments are alluded to.

The VMC Survey - I. Strategy and First Data

Abstract: Context. The new VISual and Infrared Telescope for Astronomy (VISTA) has started operations. Over its first five years it will be col lecting data for six Public Surveys, one of which is the near-infrared Y JKs VISTA survey of the Magellanic Clouds system (VMC). This survey comprises the Large Magellanic Cloud (LMC), the Small Magellanic Cloud, the Magellanic Bridge connecting the two galaxies and two fields in the Magellanic Stream. Aims. This paper provides an overview of the VMC survey strategy and presents first science results. The main goals of the VMC sur vey are the determination of the spatially-resolved star-form ation history and the three-dimensional structure of the Magellanic system. The VMC survey is therefore designed to reach stars as faint as the ol dest main sequence turn-off point and to constrain the mean magnitude of pulsating variables such as RR Lyrae stars and Cepheids. This paper focuses on observations of VMC fields in the LMC obtained between November 2009 and March 2010. These observations correspond to a completeness of 7% of the planned LMC fields. Methods. The VMC data are comprised of multi-epoch observations which are executed following specific time constraints. The data were reduced using the VISTA Data Flow System pipeline with source catalogues, including astrometric and photometric corrections, produced and made available via the VISTA Science Archive. The VMC data will be released to the astronomical community following the European Southern Observatory’s Public Survey policy. The analysis of the data shows that the sensitivity in each wave band agrees with expectations. Uncertainties and completeness of the data are also derived. Results. The first science results, aimed at assessing the scientific q uality of the VMC data, include an overview of the distribution of stars in colour-magnitude and colour-colour diagrams, the detection of planetary nebulae and stellar clusters, and the Ks band light-curves of variable stars. Conclusions. The VMC survey represents a tremendous improvement, in spatial resolution and sensitivity, on previous panoramic observations of the Magellanic system in the near-infrared, providing a powerful complement to deep observations at other wavelengths.

The persistent exclusion of older patients from ongoing clinical trials regarding heart failure.

Abstract: Methods: In the context of the Increasing the PaRticipation of the ElDerly in Clinical Trials (PREDICT) study, data from ongoing clinical trials regarding heart failure were extracted from the World Health Organization Clinical Trials Registry Platform on December 1, 2008. Main outcome measures were the proportion of trials excluding patients by an arbitrary upper age limit or by other exclusion criteria that might indirectly cause limited recruitment of older individuals. We classified exclusion criteria into 2 categories: justified or poorly justified. Results: Among 251 trials investigating treatments for heart failure, 64 (25.5%) excluded patients by an arbitrary upper age limit. Such exclusion was significantly more common in trials conducted in the European Union than in the United States (31/96 [32.3%] vs 17/105 [16.2%];P=.007) and in drug trials sponsored by public institutions vs those by private entities (21/59 [35.6%] vs 5/36 [13.9%];P=.02). Overall, 109 trials (43.4%) on heart failure had 1 or more poorly justified exclusion criteria that could limit the inclusion of older individuals. A similar proportion of clinical trials with poorly justified exclusion criteria was found in pharmacologic and nonpharmacologic trials. Conclusion: Despite the recommendations of national and international regulatory agencies, exclusion of older individuals from ongoing trials regarding heart failure continues to be widespread.

The VLT-FLAMES Tarantula Survey: I. Introduction and observational overview⋆

Abstract: The VLT-FLAMES Tarantula Survey (VFTS) is an ESO Large Programme that has obtained multi-epoch optical spectroscopy of over 800 massive stars in the 30 Doradus region of the Large Magellanic Cloud (LMC). Here we introduce our scientific motivations and give an overview of the survey targets, including optical and near-infrared photometry and comprehensive details of the data reduction. One of the principal objectives was to detect massive binary systems via variations in their radial velocities, thus shaping the multi-epoch observing strategy. Spectral classifications are given for the massive emission-line stars observed by the survey, including the discovery of a new Wolf-Rayet star (VFTS 682, classified as WN5h), 2' to the northeast of R136. To illustrate the diversity of objects encompassed by the survey, we investigate the spectral properties of sixteen targets identified by Gruendl & Chu from Spitzer photometry as candidate young stellar objects or stars with notable mid-infrared excesses. Detailed spectral classification and quantitative analysis of the O- and B-type stars in the VFTS sample, paying particular attention to the effects of rotational mixing and binarity, will be presented in a series of future articles to address fundamental questions in both stellar and cluster evolution.

Alcohols as alternative fuels: An overview

Abstract: Due to the phase out of lead in all gasoline grades and the adverse health and environmental effects of MTBE, the synthesis of higher alcohols, particularly ethanol, from synthesis gas has drawn considerable interest. Low molecular weight alcohols such as ethanol have replaced other additives as octane boosters in automotive fuels. Adding alcohols to petroleum products allows the fuel to combust more completely due to the presence of oxygen, which increases the combustion efficiency and reduces air pollution. The presence of alcohols in fuel causes corrosion to metallic fuel system components. In order to make the best use of alcohols as alternative fuels; one can redesign the engine or the vehicle can be redesign or one can blend in one or more additives to the ethanol or methanol to improve its characteristics. Catalytic conversion of synthesis gas to alcohols is advantageous, as this uses various renewable and non-renewable carbon resources. Different catalytic systems can be used for synthesizing higher alcohols from synthesis gas. Depending on the process conditions and the catalyst used, the reaction mechanism varies and the products include primary and secondary alcohols of both normal and branched carbon chains. The present paper includes an overview of the processes and catalysts used depending on the production of specific alcohols, as well as, the reaction mechanisms currently accepted. Transition metal-promoted alkali-modified molybdenum sulphide catalysts are considered to be more attractive to improve CO hydrogenation and for the production of linear alcohols.

Assessment of professionalism: Recommendations from the Ottawa 2010 Conference

Abstract: Over the past 25 years, professionalism has emerged as a substantive and sustained theme, the operationalization and measurement of which has become a major concern for those involved in medical education. However, how to go about establishing the elements that constitute appropriate professionalism in order to assess them is difficult. Using a discourse analysis approach, the International Ottawa Conference Working Group on Professionalism studied some of the dominant notions of professionalism, and in particular the implications for its assessment. The results presented here reveal different ways of thinking about professionalism that can lead towards a multi-dimensional, multi-paradigmatic approach to assessing professionalism at different levels: individual, inter-personal, societal–institutional. Recommendations for research about professionalism assessment are also presented.

Evaluation of patient reporting of adverse drug reactions to the UK 'Yellow Card Scheme': literature review, descriptive and qualitative analyses, and questionnaire surveys.

Abstract: Background: The monitoring of adverse drug reactions (ADRs) through pharmacovigilance is vital to patient safety. Spontaneous reporting of ADRs is one method of pharmacovigilance, and in the UK this is undertaken through the Yellow Card Scheme (YCS). Yellow Card reports are submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) by post, telephone or via the internet. The MHRA electronically records and reviews information submitted so that important safety issues can be detected. While previous studies have shown differences between patient and healthcare professional (HCP) reports for the types of drugs and reactions reported, relatively little is known about the pharmacovigilance impact of patient reports. There have also been few studies on the views and experiences of patients/consumers on the reporting of suspected ADRs. Objectives: To evaluate the pharmacovigilance impact of patient reporting of ADRs by analysing reports of suspected ADRs from the UK YCS and comparing reports from patients and HCPs. To elicit the views and experiences of patients and the public about patient reporting of ADRs. Design: (1) Literature review and survey of international experiences of consumer reporting of ADRs; (2) descriptive analysis of Yellow Card reports; (3) signal generation analysis of Yellow Card reports; (4) qualitative analysis of Yellow Card reports; (5) questionnaire survey of patients reporting on Yellow Cards; (6) qualitative analysis of telephone interviews with patient reporters to the scheme; (7) qualitative analysis of focus groups and usability testing of the patient YCS; and (8) national omnibus telephone survey of public awareness of the YCS. Participants: Patients (n = 5180) and HCPs (n = 20,949) submitting Yellow Card reports from October 2005 to September 2007. Respondents to questionnaire survey (n = 1362). Participants at focus groups and usability testing sessions (n = 40). National omnibus telephone survey (n = 2028). Setting: The literature review included studies in English from across the world. All other components included populations from the UK; the omnibus survey was restricted to Great Britain. Interventions: None. Main outcome measures: Characteristics of patient reports: types of drug and suspected ADR reported; seriousness of reports; and content of reports. The relative contributions of patient reports and of HCP reports to signal generation. Views and experiences of patient reporters. Views of members of the public about the YCS, including user-friendliness and usability of different ways of patient reporting. Public awareness of the YCS. Suggestions for improving patient reporting to the YCS. Results: Compared with HCPs, patient reports to the YCS contained a higher median number of suspected ADRs per report, and described reactions in more detail. The proportions of reports categorised as 'serious' were similar; the patterns of drugs and reactions reported differed. Patient reports were richer in their descriptions of reactions than those from HCPs, and more often noted the effects of ADRs on patients' lives. Combining patient and HCP reports generated more potential signals than HCP reports alone; some potential signals in the 'HCP-only' data set were lost when combined with patient reports, but fewer than those gained; the addition of patient reports to HCP reports identified 47 new 'serious' reactions not previously included in 'Summaries of Product Characteristics'. Most patient reporters found it fairly easy to make reports, although improvements to the scheme were suggested, including greater publicity and the redesign of web- and paper-based reporting systems. Among members of the public, 8.5% were aware of the YCS in 2009. Conclusions: Patient reporting of suspected ADRs has the potential to add value to pharmacovigilance by reporting types of drugs and reactions different from those reported by HCPs; generating new potential signals; and describing suspected ADRs in enough detail to provide useful information on likely causality and impact on patients' lives. These findings suggest that further promotion of patient reporting to the YCS is justified, along with improvements to existing reporting systems. In order of priority, future work should include further investigation of (1) the pharmacovigilance impact of patient reporting in a longer-term study; (2) the optimum approach to signal generation analysis of patient and HCP reports; (3) the burden of ADRs in terms of impact on patients' lives; (4) the knowledge and attitudes of HCPs towards patient reporting of ADRs; (5) the value of using patient reports of ADRs to help other patients and HCPs who are seeking information on patient experiences of ADRs; and (6) the impact of increasing publicity and/or enhancements to reporting systems on the numbers and types of Yellow Card reports from patients. Funding: The National Institute for Health Research Health Technology Assessment programme.

Inter-disciplinary perspectives on processes in the hyporheic zone

Abstract: The interface between groundwater and surface water within riverine/riparian ecosystems--the hyporheic zone (HZ)--is experiencing a rapid growth of research interest from a range of scientific disciplines, often with different perspectives. The majority of the multi-disciplinary research aims to elucidate HZ process dynamics and their importance for surface water and groundwater ecohydrology and biogeochemical cycling. This paper presents a critical inter-disciplinary review of recent advances of research centred on the HZ and highlights the current state of knowledge regarding hydrological, biogeochemical and ecohydrological process understanding. The spatial and temporal variability of surface water and groundwater exchange (hyporheic exchange flows), biogeochemical cycling and heat exchange (thermal regime) are considered in relation to both experimental measurements and modelling of these phenomena. We explore how this knowledge has helped to increase our understanding of HZ ecohydrology, and particularly its invertebrate community, the processing of organic matter, trophic cascading and ecosystem engineering by macrophytes and other organisms across a range of spatial and temporal scales. In addition to providing a detailed review of HZ functions, we present an inter-disciplinary perspective on how to advance and integrate HZ process understanding across traditional discipline boundaries. We therefore attempt to highlight knowledge gaps and research needs within the individual disciplines and demonstrate how innovations and advances in research, made within traditional subject-specific boundaries (e.g. hydrology, biochemistry and ecology), can be used to enhance inter-disciplinary scientific progress by cross-system comparisons and fostering of greater dialogue between scientific disciplines.

Surveying the Agents of Galaxy Evolution in the Tidally Stripped, Low Metallicity Small Magellanic Cloud (SAGE-SMC). I. Overview

Abstract: The Small Magellanic Cloud (SMC) provides a unique laboratory for the study of the lifecycle of dust given its low metallicity (~1/5 solar) and relative proximity (~60 kpc). This motivated the SAGE-SMC (Surveying the Agents of Galaxy Evolution in the Tidally Stripped, Low Metallicity Small Magellanic Cloud) Spitzer Legacy program with the specific goals of studying the amount and type of dust in the present interstellar medium, the sources of dust in the winds of evolved stars, and how much dust is consumed in star formation. This program mapped the full SMC (30 deg^2) including the body, wing, and tail in seven bands from 3.6 to 160 μm using IRAC and MIPS on the Spitzer Space Telescope. The data were reduced and mosaicked, and the point sources were measured using customized routines specific for large surveys. We have made the resulting mosaics and point-source catalogs available to the community. The infrared colors of the SMC are compared to those of other nearby galaxies and the 8 μm/24 μm ratio is somewhat lower than the average and the 70 μm/160 μm ratio is somewhat higher than the average. The global infrared spectral energy distribution (SED) shows that the SMC has approximately 1/3 the aromatic emission/polycyclic aromatic hydrocarbon abundance of most nearby galaxies. Infrared color-magnitude diagrams are given illustrating the distribution of different asymptotic giant branch stars and the locations of young stellar objects. Finally, the average SED of H II/star formation regions is compared to the equivalent Large Magellanic Cloud average H II/star formation region SED. These preliminary results will be expanded in detail in subsequent papers.

Applying practice theory to the study of consumption: Theoretical and methodological considerations

Abstract: In the context of continuing debate in social theory and philosophy about the structure-agency problematic, recent years have seen scholars (re)turn to this theoretical complexity through so-called theories of social practices. Practice theories are a set of cultural and philosophical accounts that focus on the conditions surrounding the practical carrying out of social life. It has roots in the philosophy of Heidegger and Wittgenstein and social scientific roots in the work of early Bourdieu, early Giddens, late Foucault and Butler. Their insights have recently become fused in a composite philosophical ontology of practices developed by Theodore Schatzki (1996, 2002) and colleagues (Schatzki et al., 2001). Together with the useful theoretical mapping provided by Reckwitz (2002) – who sketches practice theory as an ideal type, drawing out its peculiarities through a contrast with theoretical narratives in the broader domain of ‘cultural theories’ – it could be argued that practice theories have come to occupy salient theoretical space across the social sciences and humanities. When Reckwitz (2002) drafted his overview, the principles of these perspectives had already made inroads in ‘science studies, gender studies and organizational studies’ (p. 257). In recent years, this has spread to include anthropology, cultural studies, design studies, environment and

The state of the gas and the relation between gas and star formation at low metallicity: the small magellanic cloud

Abstract: We compare atomic gas, molecular gas, and the recent star formation rate (SFR) inferred from H{alpha} in the Small Magellanic Cloud (SMC). By using infrared dust emission and local dust-to-gas ratios, we construct a map of molecular gas that is independent of CO emission. This allows us to disentangle conversion factor effects from the impact of metallicity on the formation and star formation efficiency of molecular gas. On scales of 200 pc to 1 kpc (where the distributions of H{sub 2} and star formation match well) we find a characteristic molecular gas depletion time of {tau}{sup mol} d{sub ep} {approx} 1.6 Gyr, similar to that observed in the molecule-rich parts of large spiral galaxies on similar spatial scales. This depletion time shortens on much larger scales to {approx}0.6 Gyr because of the presence of a diffuse H{alpha} component, and lengthens on much smaller scales to {approx}7.5 Gyr because the H{alpha} and H{sub 2} distributions differ in detail. We estimate the systematic uncertainties in our dust-based {tau}{sup mol}{sub dep} measurement to be a factor of {approx}2-3. We suggest that the impact of metallicity on the physics of star formation in molecular gas has at most this magnitude, rather than the factormore » of {approx}40 suggested by the ratio of SFR to CO emission. The relation between SFR and neutral (H{sub 2} + H{sub i}) gas surface density is steep, with a power-law index {approx}2.2 {+-} 0.1, similar to that observed in the outer disks of large spiral galaxies. At a fixed total gas surface density the SMC has a 5-10 times lower molecular gas fraction (and star formation rate) than large spiral galaxies. We explore the ability of the recent models by Krumholz et al. and Ostriker et al. to reproduce our observations. We find that to explain our data at all spatial scales requires a low fraction of cold, gravitationally bound gas in the SMC. We explore a combined model that incorporates both large-scale thermal and dynamical equilibrium and cloud-scale photodissociation region structure and find that it reproduces our data well, as well as predicting a fraction of cold atomic gas very similar to that observed in the SMC.« less

EVIDENCE FOR ULTRA-FAST OUTFLOWS IN RADIO-QUIET ACTIVE GALACTIC NUCLEI. II. DETAILED PHOTOIONIZATION MODELING OF Fe K-SHELL ABSORPTION LINES

Abstract: X-ray absorption line spectroscopy has recently shown evidence for previously unknown Ultra-fast Outflows (UFOs) in radio-quiet active galactic nuclei (AGNs). These have been detected essentially through blueshifted Fe XXV/XXVI K-shell transitions. In the previous paper of this series we defined UFOs as those highly ionized absorbers with an outflow velocity higher than 10,000 km s–1 and assessed the statistical significance of the associated blueshifted absorption lines in a large sample of 42 local radio-quiet AGNs observed with XMM-Newton. The present paper is an extension of that work. First, we report a detailed curve of growth analysis of the main Fe XXV/XXVI transitions in photoionized plasmas. Then, we estimate an average spectral energy distribution for the sample sources and directly model the Fe K absorbers in the XMM-Newton spectra with the detailed Xstar photoionization code. We confirm that the frequency of sources in the radio-quiet sample showing UFOs is >35% and that the majority of the Fe K absorbers are indeed associated with UFOs. The outflow velocity distribution spans from ~10,000 km s–1 (~0.03c) up to ~100,000 km s–1 (~0.3c), with a peak and mean value of ~42,000 km s–1 (~0.14c). The ionization parameter is very high and in the range log ξ ~ 3-6 erg s–1 cm, with a mean value of log ξ ~ 4.2 erg s–1 cm. The associated column densities are also large, in the range N H ~ 1022-1024 cm–2, with a mean value of N H ~ 1023 cm–2. We discuss and estimate how selection effects, such as those related to the limited instrumental sensitivity at energies above 7 keV, may hamper the detection of even higher velocities and higher ionization absorbers. We argue that, overall, these results point to the presence of extremely ionized and possibly almost Compton-thick outflowing material in the innermost regions of AGNs. This also suggests that UFOs may potentially play a significant role in the expected cosmological feedback from AGNs and their study can provide important clues on the connection between accretion disks, winds, and jets.

'I like to go out to be energised by different people': an exploratory analysis of mobility and wellbeing in later life

Abstract: This paper adds to the growing number of studies about mobility and wellbeing in later life. It proposes a broader understanding of mobility than movement through physical space. Drawing on the ‘mobility turn’ in the social sciences, we conceptualise mobility as the overcoming of any type of distance between a here and a there, which can be situated in physical, electronic, social, psychological or other kinds of space. Using qualitative data from 128 older people in County Durham, England, we suggest that mobility and wellbeing influence each other in many different ways. Our analysis extends previous research in various ways. First, it shows that mobility of the self – a mental disposition of openness and willingness to connect with the world – is a crucial driver of the relation between mobility and wellbeing. Second, while loss of mobility as physical movement can and often does affect older people's sense of wellbeing adversely, this is not necessarily so; other mobilities can at least to some extent compensate for the loss of mobility in physical space. Finally, wellbeing is also enhanced through mobility as movement in physical space because the latter enables independence or subjectively experienced autonomy, as well as inter-dependence in the sense of relatively equal and reciprocal social relations with other people.

Evidence for ultra-fast outflows in radio-quiet AGNs: II - detailed photo-ionization modeling of Fe K-shell absorption lines

Abstract: X-ray absorption line spectroscopy has recently shown evidence for previously unknown Ultra-fast Outflows (UFOs) in radio-quiet AGNs. In the previous paper of this series we defined UFOs as those absorbers with an outflow velocity higher than 10,000km/s and assessed the statistical significance of the associated blueshifted FeK absorption lines in a large sample of 42 local radio-quiet AGNs observed with XMM-Newton. In the present paper we report a detailed curve of growth analysis and directly model the FeK absorbers with the Xstar photo-ionization code. We confirm that the frequency of sources in the radio-quiet sample showing UFOs is >35%. The outflow velocity distribution spans from \sim10,000km/s (\sim0.03c) up to \sim100,000km/s (\sim0.3c), with a peak and mean value of \sim42,000km/s (\sim0.14c). The ionization parameter is very high and in the range log\xi 3-6erg s^{-1} cm, with a mean value of log\xi 4.2 erg s^{-1} cm. The associated column densities are also large, in the range N_H\sim10^{22}-10^{24} cm^{-2}, with a mean value of N_H\sim10^{23} cm^{-2}. We discuss and estimate how selection effects, such as those related to the limited instrumental sensitivity at energies above 7keV, may hamper the detection of even higher velocities and higher ionization absorbers. We argue that, overall, these results point to the presence of extremely ionized and possibly almost Compton thick outflowing material in the innermost regions of AGNs. This also suggests that UFOs may potentially play a significant role in the expected cosmological feedback from AGNs and their study can provide important clues on the connection between accretion disks, winds and jets.

Convective-reactive Proton-12C Combustion in Sakurai's Object (V4334 Sagittarii) and Implications for the Evolution and Yields from the First Generations of Stars

Abstract: Depending on mass and metallicity as well as evolutionary phase, stars occasionally experience convectivereactive nucleosynthesis episodes. We specifically investigate the situation when nucleosynthetically unprocessed, H-rich material is convectively mixed with a He-burning zone, for example in convectively unstable shell on top of electron-degenerate cores in AGB stars, young white dwarfs or X-ray bursting neutron stars. Such episodes are frequently encountered in stellar evolution models of stars of extremely low or zero metal content, such as the first stars. We have carried out detailed nucleosynthesis simulations based on stellar evolution models and informed by hydrodynamic simulations. We focus on the convective-reactive episode in the very-late thermal pulse star Sakurai’s object (V4334 Sagittarii). Asplund et al. (1999) determined the abundances of 28 elements, many of which are highly non-solar, ranging from H, He and Li all the way to Ba and La, plus the C isotopic ratio. Our simulations show that the mixing evolution according to standard, one-dimensional stellar evolution models implies neutron densities in the He intershell (. few 10 11 cm -3 ) that are too low to obtain a significant neutron capture nucleosynthesis on the heavy elements. We have carried out 3D hydrodynamic He-shell flash convection simulations in 4 geometry to study the entrainment of H-rich material. Guided by these simulations we assume that the ingestion process of H into the He-shell convection zone leads only after some delay time to a sufficient entropy barrier that splits the convection zone into the original one driven by He-burning and a new one driven by the rapid burning of ingested H. By making such mixing assumptions that are motivated by our hydrodynamic simulations we obtain significantly higher neutron densities ( few 10 15 cm -3 ) and reproduce the key observed abundance trends found in Sakurai’s object. These include an overproduction of Rb, Sr and Y by about 2 orders of magnitude higher than the overproduction of Ba and La. Such a peculiar nucleosynthesis signature is impossible to obtain with the mixing predictions in our one-dimensional stellar evolution models. The simulated Li abundance and the isotopic ratio 12 C/ 13 C are as well in agreement with observations. Details of the observed heavy element abundances can be used as a sensitive diagnostic tool for the neutron density, for the neutron exposure and, in general, for the physics of the convective-reactive phases in stellar evolution. For example, the high elemental ratio Sc/Ca and the high Sc production indicate high neutron densities. The diagnostic value of such abundance markers depends on uncertain nuclear physics input. We determine how our results depend on uncertainties of nuclear reaction rates, for example for the 13 C(; n) 16 O reaction. Subject headings: stars: AGB and post-AGB — stars: abundances — stars: evolution — stars: interior — stars: individual (V4334 Sagittarii) — physical data and processes: hydrodynamics — physical data and processes: nuclear reactions, nucleosynthesis, abundances

Towards a consensus on diagnostic criteria, measurement and trial design of the premenstrual disorders : the ISPMD Montreal consensus

Abstract: Premenstrual disorders (PMD) are characterised by a cluster of somatic and psychological symptoms of varying severity that occur during the luteal phase of the menstrual cycle and resolve during menses (Freeman and Sondheimer, Prim Care Companion J Clin Psychiatry 5:30–39, 2003; Halbreich, Gynecol Endocrinol 19:320–334, 2004). Although PMD have been widely recognised for many decades, their precise cause is still unknown and there are no definitive, universally accepted diagnostic criteria. To consider this issue, an international multidisciplinary group of experts met at a face-to-face consensus meeting to review current definitions and diagnostic criteria for PMD. This was followed by extensive correspondence. The consensus group formally became established as the International Society for Premenstrual Disorders (ISPMD). The inaugural meeting of the ISPMD was held in Montreal in September 2008. The primary aim was to provide a unified approach for the diagnostic criteria of PMD, their quantification and guidelines on clinical trial design. This report summarises their recommendations. It is hoped that the criteria proposed here will inform discussions of the next edition of the World Health Organisation’s International Classification of Diseases (ICD-11), and the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria that are currently under consideration. It is also hoped that the proposed definitions and guidelines could be used by all clinicians and investigators to provide a consistent approach to the diagnosis and treatment of PMD and to aid scientific and clinical research in this field.