Potential of lipid core peptide technology as a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens

This study demonstrates the effectiveness of a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens by use of lipid core peptide (LCP) technology. An LCP formulation incorporating two different protective epitopes of the surface antiphagocytic M protein of group A streptococci (GAS)-the causative agents of rheumatic fever and subsequent rheumatic heart disease-was tested in a murine parenteral immunization and GAS challenge model. Mice were immunized with the LCP-GAS formulation, which contains an M protein amino-terminal type-specific peptide sequence (8830) in combination with a conserved non-host-cross-reactive carboxy-terminal C-region peptide sequence (J8) of the M protein. Our data demonstrated immunogenicity of the LCP-8830-J8 formulation in B10.BR mice when coadministered in complete Freund's adjuvant and in the absence of a conventional adjuvant. In both cases, immunization led to induction of high-titer GAS peptide-specific serum immunoglobulin G antibody responses and induction of highly opsonic antibodies that did not cross-react with human heart tissue proteins. Moreover, mice were completely protected from GAS infection when immunized with LCP-8830-J8 in the presence or absence of a conventional adjuvant. Mice were not protected, however, following immunization with an LCP formulation containing a control peptide from a Schistosoma sp. These data support the potential of LCP technology in the development of novel self-adjuvanting multi-antigen component vaccines and point to the potential application of this system in the development of human vaccines against infectious diseases.

Protocols for listing threatened species can forecast extinction

Risk-ranking protocols are used widely to classify the conservation status of the world's species. Here we report on the first empirical assessment of their reliability by using a retrospective study of 18 pairs of bird and mammal species (one species extinct and the other extant) with eight different assessors. The performance of individual assessors varied substantially, but performance was improved by incorporating uncertainty in parameter estimates and consensus among the assessors. When this was done, the ranks from the protocols were consistent with the extinction outcome in 70-80% of pairs and there were mismatches in only 10-20% of cases. This performance was similar to the subjective judgements of the assessors after they had estimated the range and population parameters required by the protocols, and better than any single parameter. When used to inform subjective judgement, the protocols therefore offer a means of reducing unpredictable biases that may be associated with expert input and have the advantage of making the logic behind assessments explicit. We conclude that the protocols are useful for forecasting extinctions, although they are prone to some errors that have implications for conservation. Some level of error is to be expected, however, given the influence of chance on extinction. The performance of risk assessment protocols may be improved by providing training in the application of the protocols, incorporating uncertainty in parameter estimates and using consensus among multiple assessors, including some who are experts in the application of the protocols. Continued testing and refinement of the protocols may help to provide better absolute estimates of risk, particularly by re-evaluating how the protocols accommodate missing data.

Evaluation of WOMAC 20, 50, 70 response criteria in patients treated with hylan G-F 20 for knee osteoarthritis

Objective: A secondary analysis of a previously conducted one year randomised controlled trial to evaluate the capacity of responder criteria based on the WOMAC index to detect between treatment group differences. Methods: 255 patients with knee osteoarthritis were randomised to appropriate care with hylan G-F 20'' (AC+H) or appropriate care without hylan G-F 20'' (AC). In the original analysis, two definitions of patient response from baseline to month 12 were used: ( 1) at least a 20% reduction in WOMAC pain score ( WOMAC 20P); ( 2) at least a 20% reduction in WOMAC pain score and at least a 20% reduction in either WOMAC function or stiffness score ( WOMAC 20PFS). For this analysis, a responder was identified using 50% and 70% minimum clinically important response levels to investigate how increasing response affects the ability to detect treatment group differences. Results: The hylan G- F 20 group had numerically more responders using all patient responder criteria. Increasing the response level from 20% to 50% detected similar differences between treatment groups (25% to 29%). Increasing the response level to 70% reduced the differences between treatment groups (11% to 12%) to a point where the differences were not significant after Bonferroni adjustment. Conclusions: These results provide evidence for incorporating response levels ( WOMAC 50) in clinical trials. While differences at the highest threshold ( WOMAC 70) were not statistically detectable, an appropriately powered study may be capable of detecting differences even at this very high level of improvement.

Objectives for multiple-species conservation planning

The first step in conservation planning is to identify objectives. Most stated objectives for conservation, such as to maximize biodiversity outcomes, are too vague to be useful within a decision-making framework. One way to clarify the issue is to define objectives in terms of the risk of extinction for multiple species. Although the assessment of extinction risk for single species is common, few researchers have formulated an objective function that combines the extinction risks of multiple species. We sought to translate the broad goal of maximizing the viability of species into explicit objectives for use in a decision-theoretic approach to conservation planning. We formulated several objective functions based on extinction risk across many species and illustrated the differences between these objectives with simple examples. Each objective function was the mathematical representation of an approach to conservation and emphasized different levels of threat Our objectives included minimizing the joint probability of one or more extinctions, minimizing the expected number of extinctions, and minimizing the increase in risk of extinction from the best-case scenario. With objective functions based on joint probabilities of extinction across species, any correlations in extinction probabilities bad to be known or the resultant decisions were potentially misleading. Additive objectives, such as the expected number of extinctions, did not produce the same anomalies. We demonstrated that the choice of objective function is central to the decision-making process because alternative objective functions can lead to a different ranking of management options. Therefore, decision makers need to think carefully in selecting and defining their conservation goals.

Evidence and implications of multiple paradigms in accounting knowledge production

This paper uses evidence gathered in two perception studies ofAustralasian and British accounting academics to reflect on aspects of the knowledge production systemwithin accounting academe. We provide evidence of the representation of multiple paradigms in many journals that are scored by participants as being of high quality. Indeed most of the journals we surveyed are perceived by accounting academics as incorporating research from more than one paradigm. It is argued that this ‘catholic’ approach by journal editors and the willingness of many respondents in our surveys to score journals highly on material they publish from both paradigm categories reflects a balanced acceptance of the multi-paradigmatic state of accounting research. Our analysis is set within an understanding of systems of accounting knowledge production as socially constructed and as playing an important role in the distribution of power and reward in the academy. We explore the impact of our results on concerns emerging from the work of a number of authors who carefully expose localised 'elites'. The possibilities for a closer relationship between research emerging from a multi-paradigm discipline and policy setting and practice are also discussed. The analysis provides a sense of optimism that the broad constituency of accounting academics operates within an environment conducive for the exchange of ideas. That optimism is dampened by concerns about the impact of local 'elites' and the need for more research on their impact on accounting academe.

Digital communication networks incorporating mobile data terminals

The use of digital communication systems is increasing very rapidly. This is due to lower system implementation cost compared to analogue transmission and at the same time, the ease with which several types of data sources (data, digitised speech and video, etc.) can be mixed. The emergence of packet broadcast techniques as an efficient type of multiplexing, especially with the use of contention random multiple access protocols, has led to a wide-spread application of these distributed access protocols in local area networks (LANs) and a further extension of them to radio and mobile radio communication applications. In this research, a proposal for a modified version of the distributed access contention protocol which uses the packet broadcast switching technique has been achieved. The carrier sense multiple access with collision avoidance (CSMA/CA) is found to be the most appropriate protocol which has the ability to satisfy equally the operational requirements for local area networks as well as for radio and mobile radio applications. The suggested version of the protocol is designed in a way in which all desirable features of its precedents is maintained. However, all the shortcomings are eliminated and additional features have been added to strengthen its ability to work with radio and mobile radio channels. Operational performance evaluation of the protocol has been carried out for the two types of non-persistent and slotted non-persistent, through mathematical and simulation modelling of the protocol. The results obtained from the two modelling procedures validate the accuracy of both methods, which compares favourably with its precedent protocol CSMA/CD (with collision detection). A further extension of the protocol operation has been suggested to operate with multichannel systems. Two multichannel systems based on the CSMA/CA protocol for medium access are therefore proposed. These are; the dynamic multichannel system, which is based on two types of channel selection, the random choice (RC) and the idle choice (IC), and the sequential multichannel system. The latter has been proposed in order to supress the effect of the hidden terminal, which always represents a major problem with the usage of the contention random multiple access protocols with radio and mobile radio channels. Verification of their operation performance evaluation has been carried out using mathematical modelling for the dynamic system. However, simulation modelling has been chosen for the sequential system. Both systems are found to improve system operation and fault tolerance when compared to single channel operation.

Incorporating sentiment prior knowledge for weakly supervised sentiment analysis

This article presents two novel approaches for incorporating sentiment prior knowledge into the topic model for weakly supervised sentiment analysis where sentiment labels are considered as topics. One is by modifying the Dirichlet prior for topic-word distribution (LDA-DP), the other is by augmenting the model objective function through adding terms that express preferences on expectations of sentiment labels of the lexicon words using generalized expectation criteria (LDA-GE). We conducted extensive experiments on English movie review data and multi-domain sentiment dataset as well as Chinese product reviews about mobile phones, digital cameras, MP3 players, and monitors. The results show that while both LDA-DP and LDAGE perform comparably to existing weakly supervised sentiment classification algorithms, they are much simpler and computationally efficient, rendering themmore suitable for online and real-time sentiment classification on the Web. We observed that LDA-GE is more effective than LDA-DP, suggesting that it should be preferred when considering employing the topic model for sentiment analysis. Moreover, both models are able to extract highly domain-salient polarity words from text.

Designing multiple user perspectives and functionality for clinical decision support systems

Clinical Decision Support Systems (CDSSs) need to disseminate expertise in formats that suit different end users and with functionality tuned to the context of assessment. This paper reports research into a method for designing and implementing knowledge structures that facilitate the required flexibility. A psychological model of expertise is represented using a series of formally specified and linked XML trees that capture increasing elements of the model, starting with hierarchical structuring, incorporating reasoning with uncertainty, and ending with delivering the final CDSS. The method was applied to the Galatean Risk and Safety Tool, GRiST, which is a web-based clinical decision support system (www.egrist.org) for assessing mental-health risks. Results of its clinical implementation demonstrate that the method can produce a system that is able to deliver expertise targetted and formatted for specific patient groups, different clinical disciplines, and alternative assessment settings. The approach may be useful for developing other real-world systems using human expertise and is currently being applied to a logistics domain. © 2013 Polish Information Processing Society.

Incorporating social role theory into topic models for social media content analysis

In this paper, we explore the idea of social role theory (SRT) and propose a novel regularized topic model which incorporates SRT into the generative process of social media content. We assume that a user can play multiple social roles, and each social role serves to fulfil different duties and is associated with a role-driven distribution over latent topics. In particular, we focus on social roles corresponding to the most common social activities on social networks. Our model is instantiated on microblogs, i.e., Twitter and community question-answering (cQA), i.e., Yahoo! Answers, where social roles on Twitter include "originators" and "propagators", and roles on cQA are "askers" and "answerers". Both explicit and implicit interactions between users are taken into account and modeled as regularization factors. To evaluate the performance of our proposed method, we have conducted extensive experiments on two Twitter datasets and two cQA datasets. Furthermore, we also consider multi-role modeling for scientific papers where an author's research expertise area is considered as a social role. A novel application of detecting users' research interests through topical keyword labeling based on the results of our multi-role model has been presented. The evaluation results have shown the feasibility and effectiveness of our model.

Strategic sourcing supplier selection misalignment with critical success factors:findings from multiple case studies in Germany and the United Kingdom

Strategic sourcing plays an important role in organisations' performance. Strategic sourcing has been researched extensively using empirical studies as well as review work, such as strategic sourcing importance, issues and challenges, processes, source selection criteria and framework. However, there is no research on critical success factors for strategic sourcing specific to industry and country. This research aims to qualitatively evaluate and understand the current role of strategic sourcing, the critical success factors for business performance and its relationship with strategic sourcing, and strategic supplier evaluation criteria from multiple stakeholders' perspectives specific to industry and country. This research studies twenty organisations from Germany and the United Kingdom (UK) covering two industry sectors - electronics manufacturing and construction. We consider five organisations from each industry sector and each country. The findings from twenty case studies reveal comparative analysis of strategic sourcing practices of two countries and two industries.

Characterization of human mesenchymal stem cells from multiple donors and the implications for large scale bioprocess development

Cell-based therapies have the potential to contribute to global healthcare, whereby the use of living cells and tissues can be used as medicinal therapies. Despite this potential, many challenges remain before the full value of this emerging field can be realized. The characterization of input material for cell-based therapy bioprocesses from multiple donors is necessary to identify and understand the potential implications of input variation on process development. In this work, we have characterized bone marrow derived human mesenchymal stem cells (BM-hMSCs) from multiple donors and discussed the implications of the measurable input variation on the development of autologous and allogeneic cell-based therapy manufacturing processes. The range of cumulative population doublings across the five BM-hMSC lines over 30 days of culture was 5.93, with an 18.2% range in colony forming efficiency at the end of the culture process and a 55.1% difference in the production of interleukin-6 between these cell lines. It has been demonstrated that this variation results in a range in the process time between these donor hMSC lines for a hypothetical product of over 13 days, creating potential batch timing issues when manufacturing products from multiple patients. All BM-hMSC donor lines demonstrated conformity to the ISCT criteria but showed a difference in cell morphology. Metabolite analysis showed that hMSCs from the different donors have a range in glucose consumption of 26.98 pmol cell−1 day−1, Lactate production of 29.45 pmol cell−1 day−1 and ammonium production of 1.35 pmol cell−1 day−1, demonstrating the extent of donor variability throughout the expansion process. Measuring informative product attributes during process development will facilitate progress towards consistent manufacturing processes, a critical step in the translation cell-based therapies.

Comments on multiple oscillatory solutions in systems with time-delay feedback

A complex Ginzburg-Landau equation subjected to local and global time-delay feedback terms is considered. In particular, multiple oscillatory solutions and their properties are studied. We present novel results regarding the disappearance of limit cycle solutions, derive analytical criteria for frequency degeneration, amplitude degeneration, frequency extrema. Furthermore, we discuss the influence of the phase shift parameter and show analytically that the stabilization of the steady state and the decay of all oscillations (amplitude death) cannot happen for global feedback only. Finally, we explain the onset of traveling wave patterns close to the regime of amplitude death.

Exploring the goals, content, and methods of entrepreneurship professors: A multiple case study

Along with the accumulation of evidence supporting the role of entrepreneurship in economic development (Acs & Armington, 2006; Kuratko, 2005, Reynolds, 2007), governments have persisted in encouraging people to become entrepreneurs (Acs & Stough, 2008; Brannback & Carsrud, 2008). These efforts have tried to reproduce the conditions under which entrepreneurship emerges. One of these conditions is to develop entrepreneurial skills among students and scientists (Fan & Foo, 2004). Entrepreneurship education within higher education has experienced a remarkable expansion in the last 20 years (Green, 2008). To develop entrepreneurial skills among students, scholars have proposed different teaching approaches. However, no clear relationship has been demonstrated between entrepreneurship education, learning outcomes, and business creation (Hostager & Decker, 1999). Despite policy makers demands for more accountability from educational institutions (Klimoski, 2007) and entrepreneurship instructors demands for consistency about what should be taught and how (Maidment, 2009), the appropriate content for entrepreneurship programs remains under constant discussion (Solomon, 2007). Entrepreneurship education is still in its infancy, professors propose diverse teaching goals and radically different teaching methods. This represents an obstacle to development of foundational and consistent curricula across the board (Cone, 2008). Entrepreneurship education is in need of a better conceptualization of the learning outcomes pursued in order to develop consistent curriculum. Many schools do not have enough qualified faculty to meet the growing student demand and a consistent curriculum is needed for faculty development. Entrepreneurship instructors and their teaching practices are of interest because they have a role in producing the entrepreneurs needed to grow the economy. This study was designed to understand instructors’ perspectives and actions related to their teaching. The sample studied consisted of eight college and university entrepreneurship instructors. Cases met predetermined criteria of importance followed maximum variation strategies. Results suggest that teaching content were consistent across participants while different teaching goals were identified: some instructors inspire and develop general skills of students while others envision the creation of a real business as the major outcome of their course. A relationship between methods reported by instructors and their disciplinary background, teaching perspective, and entrepreneurial experience was found.

Monitoring the Accuracy of Multiple Occupancy Forecasts

Corporate executives closely monitor the accuracy of their hotels' occupancy fore- casts since important decisions are based upon these predictions. This study lists the criteria for selecting an appropriate error measure. It discusses several evaluation methods focusing on statistical significance tests and demonstrates the use of two adequate evaluation methods: Mincer- Zamowitz's efficiency test and Wilcoxon's Non-Parametric Matched-Pairs Signed- Ranks test.

Group cognitive -behavioral therapy for heterogeneous anxiety disorders in children and adolescents: A multiple baseline study

This study investigated the efficacy of Group Cognitive-Behavioral Therapy (GCBT) in the treatment of heterogeneous anxiety disorders in children. A partially nonconcurrent multiple baseline across groups design was used to assess the effects of the treatment on 12 clinically referred children and adolescents between 6 and 16 years of age who met DSM-IV criteria for an anxiety disorder. Targeted diagnoses included Obsessive Compulsive Disorder, Simple Phobia, Separation Anxiety Disorder, Social Phobia, and Generalized Anxiety Disorder, with three of the children also presenting with school refusal behavior. Duration of baseline for each of the three groups varied and ran for one, two, or three weeks. Dependent measures included diagnostic status, child and parent-completed reports, and daily child and parent ratings of child anxiety severity. Results indicated that GCBT was efficacious in reducing anxious symptoms in children and adolescents treated in diagnostically heterogeneous groups, and that gains were generally maintained at 6 and 12 month follow-ups. Findings are discussed in terms of their theoretical and practical implications for the efficient treatment of children and adolescents with anxiety disorders. ^