Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium

The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary "dead end." We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.

A sensor based intelligent building assessment model

While building provides shelter for human being, the previous models for assessing the intelligence of a building seldom consider the responses of occupants. In addition, the assessment is usually conducted by an authority organization on a yearly basis, thus can seldom provide timely assistance for facility manager to improve his daily facility maintenance performance. By the extending the law of entropy into the area of intelligent building, this paper demonstrate that both energy consumption and the response of occupants are important when partially assessing the intelligence of a building. This study then develops a sensor based real time building intelligence (BI) assessment model. An experimental case study demonstrates how the model can be implemented. The developed model can address the two demerits of the previous BI assessment model.

The impact of procurement method on costs of procurement

Collaborative working methods offer the hope of reduced waste, lower tendering costs and improved outputs. The costs of tendering may be influenced by the introduction of different working methods. Transaction cost economics appears to offer an analytical framework for studying the costs of tendering, but it is more to do with providing explanations at the institutional/industry level, not at the level of individual projects. Surveys and interviews were carried out with small samples in UK. The data show that that while tendering costs are not necessarily higher in collaborative working arrangements, there is no correlation between costs of tendering and the way the work is organized. Practitioners perceive that the benefits of working in collaborative procurement routes far outweigh the costs. Tendering practices can be improved to avoid waste, and the suggested improvements include restricting selective tendering lists to 23 bidders, letting bidders know who they are competing with, reimbursing tendering costs for aborted projects and ensuring that timely and comprehensive information is provided to bidders.

Primary music education: the misrepresentation of the ideals of curricula in research

The author starts from a historical viewpoint to suggest that, at primary level, we have tended to perpetuate a nineteenth-century notion of music education. This is evident in the selection and organisation of musical content in curriculum documents, the scope of the teacher-pupil transaction implicit in these and the assumptions about music education which underpin research on practice conducted at official policy level. In light of the introduction of the 1999 Revised Primary School Curriculum, with its change in emphasis, she notes that it is timely to reconsider the situation. Central to this is the need to challenge the notion of music as a set of delineated skills, to explore the relationship between the primary teacher and music, and to move towards a notion of research which acknowledges the richness of multiple interpretations teachers bring to the curriculum.

The benefits of providing benefit information in a patient information leaflet

Objective: To examine the effects of providing two different types of written information about medicine benefits in a patient information leaflet (PIL). Setting: Participants were 358 adult volunteers from the general population recruited from a London railway station and central Reading. Method: The study used a controlled empirical methodology in which people were given a hypothetical, but realistic, scenario about visiting their doctor and being prescribed medication. They then read an information leaflet about the medicine that contained neither, one, or both benefit statements, and finally completed a number of Likert rating scales. Outcome measures included perceived satisfaction and helpfulness of the information, effectiveness and appropriateness of the medicine, benefit and risk to health, and intention to comply. Key findings: Both types of benefit information led to significantly higher ratings on all of the measures taken. Conclusions: Provision of a relatively short ‘benefit’ statement can significantly improve people’s judgements and intention to take a medicine. The findings are important and timely as the European Union is currently considering reviewing their regulations to allow for the inclusion of limited non-promotional benefit information in PILs.

ICT implants: the invasive future of identity?

Is the human body a suitable place for a microchip? Such discussion is no longer hypothetical - in fact in reality it has not been so for some years. Restorative devices such as pacemakers and cochlear implants have become well established, yet these sophisticated devices form notably intimate links between technology and the body. More recent developments in engineering technologies have meant that the integration of silicon with biology is now reaching new levels - with devices which interact directly with the brain. As medical technologies continue to advance, their potential benefits for human enhancement will become increasingly attractive, and so we need to seriously consider where this may take us. In this paper, an attempt is made to demonstrate that, in the medical context, the foundations of more advanced implantable enhancement technologies are already notably progressed, and that they are becoming more science fact than is widely considered. A number of wider moral, ethical and legal issues stem from enhancement applications and it is difficult to foresee the social consequences, the fundamental changes on our very conception of self and the impact on our identity of adoption long term. As a result, it is necessary to acknowledge the possibilities and is timely to have debate to address the wider implications these possibilities may bring.

A study of factors contributing to late submission of course work

This case study uses log-linear modelling to investigate the interrelationships between factors that may contribute to the late submission of coursework by undergraduate students. A class of 86 computing students are considered. These students were exposed to traditional teaching methods supported by e-learning via a Managed Learning Environment (MLE). The MLE warehouses detailed data about student usage of the various areas of the environment, which can be used to interpret the approach taken to learning. The study investigates the interrelationship between these factors with the information as to whether the student handed in their course work on time or whether they were late. The results from the log-linear modelling technique show that there is an interaction between participating in Discussions within the MLE and the timely submission of course work, indicating that participants are more likely to hand in on time, than those students who do not participate.

A review on Northern Hemisphere sea-ice, storminess and the North Atlantic Oscillation: observations and projected changes

The Arctic has undergone substantial changes over the last few decades in various cryospheric and derivative systems and processes. Of these, the Arctic sea ice regime has seen some of the most rapid change and is one of the most visible markers of Arctic change outside the scientific community. This has drawn considerable attention not only from the natural sciences, but increasingly, from the political and commercial sectors as they begin to grapple with the problems and opportunities that are being presented. The possible impacts of past and projected changes in Arctic sea ice, especially as it relates to climatic response, are of particular interest and have been the subject of increasing research activity. A review of the current knowledge of the role of sea ice in the climate system is therefore timely. We present a review that examines both the current state of understanding, as regards the impacts of sea-ice loss observed to date, and climate model projections, to highlight hypothesised future changes and impacts on storm tracks and the North Atlantic Oscillation. Within the broad climate-system perspective, the topics of storminess and large-scale variability will be specifically considered. We then consider larger-scale impacts on the climatic system by reviewing studies that have focused on the interaction between sea-ice extent and the North Atlantic Oscillation. Finally, an overview of the representation of these topics in the literature in the context of IPCC climate projections is presented. While most agree on the direction of Arctic sea-ice change, the rates amongst the various projections vary greatly. Similarly, the response of storm tracks and climate variability are uncertain, exacerbated possibly by the influence of other factors. A variety of scientific papers on the relationship between sea-ice changes and atmospheric variability have brought to light important aspects of this complex topic. Examples are an overall reduction in the number of Arctic winter storms, a northward shift of mid-latitude winter storms in the Pacific and a delayed negative NAO-like response in autumn/winter to a reduced Arctic sea-ice cover (at least in some months). This review paper discusses this research and the disagreements, bringing about a fresh perspective on this issue.

Ensuring operational compliance and ethical responsibility in the regulation of ART: the HFEA, past, present, and future

Under the Public Bodies Bill 2010, the HFEA, cornerstone in the regulation of assisted reproduction technologies (ART) for the last twenty years, is due to be abolished. This implies that there is no longer a need for a dedicated regulator for ART and that the existing roles of the Authority as both operational compliance monitor, and instance of ethical evaluation, may be absorbed by existing healthcare regulators. This article presents a timely analysis of these disparate functions of the HFEA, charting reforms adopted in 2008 and assessing the impact of the current proposals. Taking assisted conception treatment as the focus activity, it will be shown that the last few years have seen a concentration on the HFEA as a technical regulator based upon the principles of Better Regulation, with little analysis of how the ethical responsibility of the Authority fits into this framework. The current proposal to abolish the HFEA continues to fail to address this crucial question. Notwithstanding the fact that the scope of the Authority's ethical role may be questioned, its abolition requires that the Government consider what alternatives exists - or need to be put in place - to provide both responsive operational regulation and a forum for ethical reflection and decision-making in an area which continues to pose regulatory challenges

The general observation period 2007 within the priority program on quantitative precipitation forecasting: concept and first results

In the year 2007 a General Observation Period (GOP) has been performed within the German Priority Program on Quantitative Precipitation Forecasting (PQP). By optimizing the use of existing instrumentation a large data set of in-situ and remote sensing instruments with special focus on water cycle variables was gathered over the full year cycle. The area of interest covered central Europe with increasing focus towards the Black Forest where the Convective and Orographically-induced Precipitation Study (COPS) took place from June to August 2007. Thus the GOP includes a variety of precipitation systems in order to relate the COPS results to a larger spatial scale. For a timely use of the data, forecasts of the numerical weather prediction models COSMO-EU and COSMO-DE of the German Meteorological Service were tailored to match the observations and perform model evaluation in a near real-time environment. The ultimate goal is to identify and distinguish between different kinds of model deficits and to improve process understanding.

The British state and the Irish rebellion of 1916: an intelligence failure or an failure of response

The teleological narrative that has dominated the handling of intelligence by the British state in the events that led up to the 1916 Irish Rebellion in Dublin has been characterised as a cocktail of incompetence and mendacity. Using new and existing archive material this article argues that both the cabinet in London and key members of the Irish Executive in Dublin were supplied with accurate and timely intelligence by the Admiralty's signals intelligence unit, the Royal Irish Constabulary and the Dublin Metropolitan Police with respect to this event. Far from being a failure of intelligence here is evidence to show that there occurred a failure of response on behalf of key decision-makers. The warnings that were given by intelligence organisations were filtered through the existing policy preferences and assumptions. As a result of these factors accurate evaluations and sound judgement were not exercised by key officials, such as Sir Matthew Nathan, in Dublin Castle.

ASSET: moving forward through feedback

Providing high quality and timely feedback to students is often a challenge for many staff in higher education as it can be both time-consuming and frustratingly repetitive. From the student perspective, feedback may sometimes be considered unhelpful, confusing and inconsistent and may not always be provided within a timeframe that is considered to be ‘useful’. The ASSET project, based at the University of Reading, addresses many of these inherent challenges by encouraging the provision of feedback that supports learning, i.e. feedback that contains elements of ‘feed-forward’, is of a high quality and is delivered in a timely manner. In particular, the project exploits the pedagogic benefits of video/audio media within a Web 2.0 context to provide a new, interactive resource, ‘ASSET’, to enhance the feedback experience for both students and staff. A preliminary analysis of both our quantitative and qualitative pedagogic data demonstrate that the ASSET project has instigated change in the ways in which both staff and students think about, deliver, and engage with feedback. For example, data from our online questionnaires and focus groups with staff and students indicate a positive response to the use of video as a medium for delivering feedback to students. In particular, the academic staff engaged in piloting the ASSET resource indicated that i) using video has made them think more, and in some cases differently, about the ways in which they deliver feedback to students and ii) they now see video as an effective means of making feedback more useful and engaging for students. Moreover, the majority of academic staff involved in the project have said they will continue to use video feedback. From the student perspective, 60% of those students whose lecturers used ASSET to provide video feedback said that “receiving video feedback encouraged me to take more notice of the feedback compared with normal methods” and 80% would like their lecturer to continue to use video as a method for providing feedback. An important aim of the project was for it to complement existing University-wide initiatives on feedback and for ASSET to become a ‘model’ resource for staff and students wishing to explore video as a medium for feedback provision. An institutional approach was therefore adopted and key members of Senior Management, academics, T&L support staff, IT support and Student Representatives were embedded within the project from the start. As with all initiatives of this kind, a major issue is the future sustainability of the ASSET resource and to have had both ‘top-down’ and ‘bottom-up’ support for the project has been extremely beneficial. In association with the project team the University is currently exploring the creation of an open-source, two-tiered video supply solution and a ‘framework’ (that other HEIs can adopt and/or adapt) to support staff in using video for feedback provision. In this way students and staff will have new opportunities to explore video and to exploit the benefits of this medium for supporting learning.

Everything and nothing project

An EPRSC ‘Partnerships for Public Engagement’ scheme 2010. FEC 122,545.56/UoR 10K everything and nothing is a performance and workshop which engages the public creatively with mathematical concepts: the Poincare conjecture, the shape of the universe, topology, and the nature of infinity are explored through an original, thought provoking piece of music theatre. Jorge Luis Borges' short story 'The Library of Babel' and the aviator Amelia Earhart’s attempt to circumnavigate the globe combine to communicate to audience key mathematical concepts of Poincare’s conjecture. The project builds on a 2008 EPSRC early development project (EP/G001650/1) and is led by an interdisciplinary team the19thstep consisting of composer Dorothy Ker, sculptor Kate Allen and mathematician Marcus du Sautoy. everything and nothing has been devised by Dorothy Ker and Kate Allen, is performed by percussionist Chris Brannick, mezzo soprano Lucy Stevens and sound designer Kelcey Swain. The UK tour targets arts-going audiences, from the Green Man Festival to the British Science Festival. Each performance is accompanied with a workshop led by Topologist Katie Steckles. Alongside the performances and workshops is a website, http://www.everythingandnothingproject.com/ The Public engagement evaluation and monitoring for the project are carried out by evaluator Bea Jefferson. The project is significant in its timely relation to contemporary mathematics and arts-science themes delivering an extensive programme of public engagement.

Predicting the annual performance of UK real estate: timeliness versus coverage

The IPD Annual Index is the largest and most comprehensive Real Estate market index available in the UK Such coverage however inevitably leads to delays in publication. In contrast there are a number of quarterly and monthly indices which are published within days of the year end but which lack the coverage in terms of size and numbers of properties. This paper analyses these smaller but more timely indices to see whether such indices can be used to predict the performance of the IPD Annual Index. Using a number of measures of forecasting accuracy it is shown that the smaller indices provide unbiased and efficient predictions of the IPD Annual Index. Such indices also significantly outperform a naive no-change model. Although no one index performs significantly better than the others. The more timely indices however do not perfectly track the IPD Annual Index. As a result any short run predictions of performance will be subject to a degree of error. Nevertheless the more timely indices, although lacking authoritative coverage, provide a valuable service to investors giving good estimates of Real Estates performance well before the publication of the IPD Annual Index.

Predicting the arrival of high-speed solar wind streams at Earth using the STEREO Heliospheric Imagers

High-speed solar wind streams modify the Earth's geomagnetic environment, perturbing the ionosphere, modulating the flux of cosmic rays into the Earth atmosphere, and triggering substorms. Such activity can affect modern technological systems. To investigate the potential for predicting the arrival of such streams at Earth, images taken by the Heliospheric Imager (HI) on the STEREO-A spacecraft have been used to identify the onsets of high-speed solar wind streams from observations of regions of increased plasma concentrations associated with corotating interaction regions, or CIRs. In order to confirm that these transients were indeed associated with CIRs and to study their average properties, arrival times predicted from the HI images were used in a superposed epoch analysis to confirm their identity in near-Earth solar wind data obtained by the Advanced Composition Explorer (ACE) spacecraft and to observe their influence on a number of salient geophysical parameters. The results are almost identical to those of a parallel superposed epoch analysis that used the onset times of the high-speed streams derived from east/west deflections in the ACE measurements of solar wind speed to predict the arrival of such streams at Earth, assuming they corotated with the Sun with a period of 27 days. Repeating the superposed epoch analysis using restricted data sets demonstrates that this technique can provide a timely prediction of the arrival of CIRs at least 1 day ahead of their arrival at Earth and that such advanced warning can be provided from a spacecraft placed 40° ahead of Earth in its orbit.