Leisure studies education: Historical trends and pedagogical futures in the United Kingdom and beyond

This paper is an attempt to stimulate debate about the decline of leisure studies and the rise of courses and subject fields defined by sport, events, tourism management. It is argued that although this decline has happened, there are two possible futures for a re-purposed leisure studies that would ensure its survival

Can general practitioner commissioning deliver equity and excellence? : Evidence from two studies of service improvement in the English NHS

Objectives: To explore some of the key assumptions underpinning the continued development of general practitioner-led commissioning in health services. Methods: Qualitative data from two studies of service improvement in the English NHS were considered against England's plans for GP-led commissioning. These data were collected through in-depth interviews with a total of 187 professionals and 99 people affected by services in 10 different primary care trust areas across England between 2008 and 2009. Results: Internationally, GPs are seen to have a central position in health systems. In keeping with this, the English policy places emphasis on the 'pivotal role' of general practitioners, considered to be ideally placed to commission in the best interests of their patients. However, our evidence suggests that general practitioners do not always have a pivotal role for all patients. Moreover, it is planned that the new commissioning groups in England will not be subject to top-down performance management and this raises the question of how agreed quality standards will be met under the proposed new system. Conclusions: This paper questions the assumption that GPs are best placed to commission health services in a way that meets quality standards and leads to equitable outcomes. There is little evidence to suggest that GPs will succeed where others have failed and a risk that, without top-down performance management, service improvement will be patchy, leading to greater, not reduced, inequity

System for improving measurement accuracy of transducer by measuring transducer temperature and resistance change using thermoelectric voltages

A constant current loop measuring system measures a property including the temperature of a sensor responsive to an external condition being measured. The measuring system includes thermocouple conductors connected to the sensor, sensing first and second induced voltages responsive to the external condition. In addition, the measuring system includes a current generator and reverser generating a constant current, and supplying the constant current to the thermocouple conductors in forward and reverse directions generating first and second measured voltages, and a determining unit receiving the first and second measured voltages from the current generator and reverser, and determining the temperature of the sensor responsive to the first and second measured voltages

The usage of mobile communication systems in the trucking industry

This article reports the findings of a mobile communications survey mailed out to over 2,000 trucking firms. The findings indicate that 68% of respondents use some form of mobile communication system in their firm. Various types of mobile communication systems were reported, including two-way pagers, one-way pagers, cell phones, two-way radio, and satellite communications. Additionally, implementation decision factors for mobile communication systems were evaluated for both users and non-users of mobile communication systems

Optimization algorithms for functional deimmunization of therapeutic proteins

<p>Abstract</p> <p>Background</p> <p>To develop protein therapeutics from exogenous sources, it is necessary to mitigate the risks of eliciting an anti-biotherapeutic immune response. A key aspect of the response is the recognition and surface display by antigen-presenting cells of epitopes, short peptide fragments derived from the foreign protein. Thus, developing minimal-epitope variants represents a powerful approach to deimmunizing protein therapeutics. Critically, mutations selected to reduce immunogenicity must not interfere with the protein's therapeutic activity.</p> <p>Results</p> <p>This paper develops methods to improve the likelihood of simultaneously reducing the anti-biotherapeutic immune response while maintaining therapeutic activity. A dynamic programming approach identifies optimal and near-optimal sets of conservative point mutations to minimize the occurrence of predicted T-cell epitopes in a target protein. In contrast with existing methods, those described here integrate analysis of immunogenicity and stability/activity, are broadly applicable to any protein class, guarantee global optimality, and provide sufficient flexibility for users to limit the total number of mutations and target MHC alleles of interest. The input is simply the primary amino acid sequence of the therapeutic candidate, although crystal structures and protein family sequence alignments may also be input when available. The output is a scored list of sets of point mutations predicted to reduce the protein's immunogenicity while maintaining structure and function. We demonstrate the effectiveness of our approach in a number of case study applications, showing that, in general, our best variants are predicted to be better than those produced by previous deimmunization efforts in terms of either immunogenicity or stability, or both factors.</p> <p>Conclusions</p> <p>By developing global optimization algorithms leveraging well-established immunogenicity and stability prediction techniques, we provide the protein engineer with a mechanism for exploring the favorable sequence space near a targeted protein therapeutic. Our mechanism not only helps identify designs more likely to be effective, but also provides insights into the interrelated implications of design choices.</p

Mapping the Pareto Optimal Design Space for a Functionally Deimmunized Biotherapeutic Candidate

The immunogenicity of biotherapeutics can bottleneck development pipelines and poses a barrier to widespread clinical application. As a result, there is a growing need for improved deimmunization technologies. We have recently described algorithms that simultaneously optimize proteins for both reduced T cell epitope content and high-level function. In silico analysis of this dual objective design space reveals that there is no single global optimum with respect to protein deimmunization. Instead, mutagenic epitope deletion yields a spectrum of designs that exhibit tradeoffs between immunogenic potential and molecular function. The leading edge of this design space is the Pareto frontier, i.e. the undominated variants for which no other single design exhibits better performance in both criteria. Here, the Pareto frontier of a therapeutic enzyme has been designed, constructed, and evaluated experimentally. Various measures of protein performance were found to map a functional sequence space that correlated well with computational predictions. These results represent the first systematic and rigorous assessment of the functional penalty that must be paid for pursuing progressively more deimmunized biotherapeutic candidates. Given this capacity to rapidly assess and design for tradeoffs between protein immunogenicity and functionality, these algorithms may prove useful in augmenting, accelerating, and de-risking experimental deimmunization efforts

Mean-field effects in the Galloway-Proctor flow

The coefficients defining the mean electromotive force in a Galloway-Proctor flow are determined. This flow shows a two-dimensional pattern and is helical. The pattern wobbles in its plane. Apart from one exception a circular motion of the flow pattern is assumed. This corresponds to one of the cases considered recently by Courvoisier, Hughes and Tobias (2006, Phys. Rev. Lett., 96, 034503). An analytic theory of the alpha effect and related effects in this flow is developed within the second-order correlation approximation and a corresponding fourth-order approximation. In the validity range of these approximations there is an alpha effect but no gamma effect, or pumping effect. Numerical results obtained with the test-field method, which are independent of these approximations, confirm the results for alpha and show that gamma is in general nonzero. Both alpha and gamma show a complex dependency on the magnetic Reynolds number and other parameters that define the flow, that is, amplitude and frequency of the wobbling motion. Some results for the magnetic diffusivity eta_t and a related quantity are given, too. Finally a result for alpha in the case of a randomly varying flow without the aforementioned circular motion is presented. This flow may be a more appropriate model for studying the alpha effect and related effects in flows that are statistical isotropic in a plane.Comment: 12 pages, 14 figures, submitted to MNRA