What have dendritic cells ever done for adjuvant design? Cellular and molecular methods for the rational development of vaccine adjuvants

Our new molecular understanding of immune priming states that dendritic cell activation is absolutely pivotal for expansion and differentiation of naïve T lymphocytes, and it follows that understanding DC activation is essential to understand and design vaccine adjuvants. This chapter describes how dendritic cells can be used as a core tool to provide detailed quantitative and predictive immunomics information about how adjuvants function. The role of distinct antigen, costimulation, and differentiation signals from activated DC in priming is explained. Four categories of input signals which control DC activation – direct pathogen detection, sensing of injury or cell death, indirect activation via endogenous proinflammatory mediators, and feedback from activated T cells – are compared and contrasted. Practical methods for studying adjuvants using DC are summarised and the importance of DC subset choice, simulating T cell feedback, and use of knockout cells is highlighted. Finally, five case studies are examined that illustrate the benefit of DC activation analysis for understanding vaccine adjuvant function.

Gradient recovery in adaptive finite-element methods for parabolic problems

We derive energy-norm a posteriori error bounds, using gradient recovery (ZZ) estimators to control the spatial error, for fully discrete schemes for the linear heat equation. This appears to be the �rst completely rigorous derivation of ZZ estimators for fully discrete schemes for evolution problems, without any restrictive assumption on the timestep size. An essential tool for the analysis is the elliptic reconstruction technique.Our theoretical results are backed with extensive numerical experimentation aimed at (a) testing the practical sharpness and asymptotic behaviour of the error estimator against the error, and (b) deriving an adaptive method based on our estimators. An extra novelty provided is an implementation of a coarsening error "preindicator", with a complete implementation guide in ALBERTA in the appendix.

Improved MATLAB GUIs for learning frequency response methods

The author developed two GUIs for asymptotic Bode plots and identification from such plots aimed at improving the learning of frequency response methods: these were presented at UKACC Control 2012. Student feedback and reflection by the author suggested various improvements to these GUIs, which have now been implemented. This paper reviews the earlier work, describes the improvements, and includes positive feedback from the students on the GUIs and how they have helped their understanding of the methods.

A comparison of methods for constructing confidence intervals after phase II/III clinical trials

Recently, in order to accelerate drug development, trials that use adaptive seamless designs such as phase II/III clinical trials have been proposed. Phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages. Using stage 1 data, an interim analysis is performed to answer phase II objectives and after collection of stage 2 data, a final confirmatory analysis is performed to answer phase III objectives. In this paper we consider phase II/III clinical trials in which, at stage 1, several experimental treatments are compared to a control and the apparently most effective experimental treatment is selected to continue to stage 2. Although these trials are attractive because the confirmatory analysis includes phase II data from stage 1, the inference methods used for trials that compare a single experimental treatment to a control and do not have an interim analysis are no longer appropriate. Several methods for analysing phase II/III clinical trials have been developed. These methods are recent and so there is little literature on extensive comparisons of their characteristics. In this paper we review and compare the various methods available for constructing confidence intervals after phase II/III clinical trials.

Control of final moisture content of food products baked in continuous tunnel ovens

There are well-known difficulties in making measurements of the moisture content of baked goods (such as bread, buns, biscuits, crackers and cake) during baking or at the oven exit; in this paper several sensing methods are discussed, but none of them are able to provide direct measurement with sufficient precision. An alternative is to use indirect inferential methods. Some of these methods involve dynamic modelling, with incorporation of thermal properties and using techniques familiar in computational fluid dynamics (CFD); a method of this class that has been used for the modelling of heat and mass transfer in one direction during baking is summarized, which may be extended to model transport of moisture within the product and also within the surrounding atmosphere. The concept of injecting heat during the baking process proportional to the calculated heat load on the oven has been implemented in a control scheme based on heat balance zone by zone through a continuous baking oven, taking advantage of the high latent heat of evaporation of water. Tests on biscuit production ovens are reported, with results that support a claim that the scheme gives more reproducible water distribution in the final product than conventional closed loop control of zone ambient temperatures, thus enabling water content to be held more closely within tolerance.

Reliability comparison of transmit/receive diversity and error control coding in low-power medium access control protocols

Low-power medium access control (MAC) protocols used for communication of energy constraint wireless embedded devices do not cope well with situations where transmission channels are highly erroneous. Existing MAC protocols discard corrupted messages which lead to costly retransmissions. To improve transmission performance, it is possible to include an error correction scheme and transmit/receive diversity. It is possible to add redundant information to transmitted packets in order to recover data from corrupted packets. It is also possible to make use of transmit/receive diversity via multiple antennas to improve error resiliency of transmissions. Both schemes may be used in conjunction to further improve the performance. In this study, the authors show how an error correction scheme and transmit/receive diversity can be integrated in low-power MAC protocols. Furthermore, the authors investigate the achievable performance gains of both methods. This is important as both methods have associated costs (processing requirements; additional antennas and power) and for a given communication situation it must be decided which methods should be employed. The authors’ results show that, in many practical situations, error control coding outperforms transmission diversity; however, if very high reliability is required, it is useful to employ both schemes together.

Bio-inspired autonomous visual vertical control of a quadrotor UAV

Near ground maneuvers, such as hover, approach and landing, are key elements of autonomy in unmanned aerial vehicles. Such maneuvers have been tackled conventionally by measuring or estimating the velocity and the height above the ground often using ultrasonic or laser range finders. Near ground maneuvers are naturally mastered by flying birds and insects as objects below may be of interest for food or shelter. These animals perform such maneuvers efficiently using only the available vision and vestibular sensory information. In this paper, the time-to-contact (Tau) theory, which conceptualizes the visual strategy with which many species are believed to approach objects, is presented as a solution for Unmanned Aerial Vehicles (UAV) relative ground distance control. The paper shows how such an approach can be visually guided without knowledge of height and velocity relative to the ground. A control scheme that implements the Tau strategy is developed employing only visual information from a monocular camera and an inertial measurement unit. To achieve reliable visual information at a high rate, a novel filtering system is proposed to complement the control system. The proposed system is implemented on-board an experimental quadrotor UAV and shown not only to successfully land and approach ground, but also to enable the user to choose the dynamic characteristics of the approach. The methods presented in this paper are applicable to both aerial and space autonomous vehicles.

A comparison of methods for treatment selection in seamless phase II/III clinical trials incorporating information on short-term endpoints

In an adaptive seamless phase II/III clinical trial interim analysis, data are used for treatment selection, enabling resources to be focused on comparison of more effective treatment(s) with a control. In this paper, we compare two methods recently proposed to enable use of short-term endpoint data for decision-making at the interim analysis. The comparison focuses on the power and the probability of correctly identifying the most promising treatment. We show that the choice of method depends on how well short-term data predict the best treatment, which may be measured by the correlation between treatment effects on short- and long-term endpoints.

Bioinspired autonomous visual vertical control of a quadrotor unmanned aerial vehicle

Near-ground maneuvers, such as hover, approach, and landing, are key elements of autonomy in unmanned aerial vehicles. Such maneuvers have been tackled conventionally by measuring or estimating the velocity and the height above the ground, often using ultrasonic or laser range finders. Near-ground maneuvers are naturally mastered by flying birds and insects because objects below may be of interest for food or shelter. These animals perform such maneuvers efficiently using only the available vision and vestibular sensory information. In this paper, the time-tocontact (tau) theory, which conceptualizes the visual strategy with which many species are believed to approach objects, is presented as a solution for relative ground distance control for unmanned aerial vehicles. The paper shows how such an approach can be visually guided without knowledge of height and velocity relative to the ground. A control scheme that implements the tau strategy is developed employing only visual information from a monocular camera and an inertial measurement unit. To achieve reliable visual information at a high rate, a novel filtering system is proposed to complement the control system. The proposed system is implemented onboard an experimental quadrotor unmannedaerial vehicle and is shown to not only successfully land and approach ground, but also to enable the user to choose the dynamic characteristics of the approach. The methods presented in this paper are applicable to both aerial and space autonomous vehicles.

Body-centric modelling, identification, and acceleration tracking control of a quadrotor UAV

This paper presents the mathematical development of a body-centric nonlinear dynamic model of a quadrotor UAV that is suitable for the development of biologically inspired navigation strategies. Analytical approximations are used to find an initial guess of the parameters of the nonlinear model, then parameter estimation methods are used to refine the model parameters using the data obtained from onboard sensors during flight. Due to the unstable nature of the quadrotor model, the identification process is performed with the system in closed-loop control of attitude angles. The obtained model parameters are validated using real unseen experimental data. Based on the identified model, a Linear-Quadratic (LQ) optimal tracker is designed to stabilize the quadrotor and facilitate its translational control by tracking body accelerations. The LQ tracker is tested on an experimental quadrotor UAV and the obtained results are a further means to validate the quality of the estimated model. The unique formulation of the control problem in the body frame makes the controller better suited for bio-inspired navigation and guidance strategies than conventional attitude or position based control systems that can be found in the existing literature.

Sample size considerations in active-control non-inferiority trials with binary data based on the odds ratio

This paper presents an approximate closed form sample size formula for determining non-inferiority in active-control trials with binary data. We use the odds-ratio as the measure of the relative treatment effect, derive the sample size formula based on the score test and compare it with a second, well-known formula based on the Wald test. Both closed form formulae are compared with simulations based on the likelihood ratio test. Within the range of parameter values investigated, the score test closed form formula is reasonably accurate when non-inferiority margins are based on odds-ratios of about 0.5 or above and when the magnitude of the odds ratio under the alternative hypothesis lies between about 1 and 2.5. The accuracy generally decreases as the odds ratio under the alternative hypothesis moves upwards from 1. As the non-inferiority margin odds ratio decreases from 0.5, the score test closed form formula increasingly overestimates the sample size irrespective of the magnitude of the odds ratio under the alternative hypothesis. The Wald test closed form formula is also reasonably accurate in the cases where the score test closed form formula works well. Outside these scenarios, the Wald test closed form formula can either underestimate or overestimate the sample size, depending on the magnitude of the non-inferiority margin odds ratio and the odds ratio under the alternative hypothesis. Although neither approximation is accurate for all cases, both approaches lead to satisfactory sample size calculation for non-inferiority trials with binary data where the odds ratio is the parameter of interest.

Infection Control in design and construction work

Objective: To clarify how infection control requirements are represented, communicated, and understood in work interactions through the medical facility construction project life cycle. To assist project participants with effective infection control management by highlighting the nature of such requirements and presenting recommendations to aid practice. Background: A 4-year study regarding client requirement representation and use on National Health Service construction projects in the United Kingdom provided empirical evidence of infection control requirement communication and understanding through design and construction work interactions. Methods: An analysis of construction project resources (e.g., infection control regulations and room data sheets) was combined with semi-structured interviews with hospital client employees and design and construction professionals to provide valuable insights into the management of infection control issues. Results: Infection control requirements are representationally indistinct but also omnipresent through all phases of the construction project life cycle: Failure to recognize their nature, relevance, and significance can result in delays, stoppages, and redesign work. Construction project resources (e.g., regulatory guidance and room data sheets) can mask or obscure the meaning of infection control issues. Conclusions: A preemptive identification of issues combined with knowledge sharing activities among project stakeholders can enable infection control requirements to be properly understood and addressed. Such initiatives should also reference existing infection control regulatory guidance and advice.

Quantifying particle size and turbulent scale dependence of dust uplift in the Sahara using aircraft measurements

The first size-resolved airborne measurements of dust fluxes and the first dust flux measurements from the central Sahara are presented and compared with a parameterization by Kok (2011a). High-frequency measurements of dust size distribution were obtained from 0.16 to 300 µm diameter, and eddy covariance fluxes were derived. This is more than an order of magnitude larger size range than previous flux estimates. Links to surface emission are provided by analysis of particle drift velocities. Number flux is described by a −2 power law between 1 and 144 µm diameter, significantly larger than the 12 µm upper limit suggested by Kok (2011a). For small particles, the deviation from a power law varies with terrain type and the large size cutoff is correlated with atmospheric vertical turbulent kinetic energy, suggesting control by vertical transport rather than emission processes. The measured mass flux mode is in the range 30–100 µm. The turbulent scales important for dust flux are from 0.1 km to 1–10 km. The upper scale increases during the morning as boundary layer depth and eddy size increase. All locations where large dust fluxes were measured had large topographical variations. These features are often linked with highly erodible surface features, such as wadis or dunes. We also hypothesize that upslope flow and flow separation over such features enhance the dust flux by transporting large particles out of the saltation layer. The tendency to locate surface flux measurements in open, flat terrain means these favored dust sources have been neglected in previous studies.

Methods to assess the effectiveness of naturally ventilated classrooms in Gauteng, South Africa

There is a tendency to reduce ventilation rates and natural or hybrid ventilation systems to ensure the conservation of energy in school buildings. However, high indoor pollutant concentration, due to natural or hybrid ventilation systems may have a significant adverse impact on the health and academic performance of pupils and students. Reviewed evidence shows that this can be detrimental to health and wellbeing in schools because of the learner density within a small area, eventually indicating that CO2 concentrations can rise to very high levels (about 4000 ppm) in classrooms during occupancy periods. In South Africa’s naturally ventilated classrooms, it is not clear whether the environmental conditions are conducive for learning. In addition, natural ventilation will be minimized given the fact that in cold, wet or windy weather, doors and windows will commonly remain closed. Evidence from literature based studies indicates that the significance of ventilation techniques is not understood satisfactorily and additional information concerning naturally ventilated schools has to be provided for better design and policy formulation. To develop a thorough understanding of the environments in classrooms, many other parameters have to be considered as well, such as outdoor air quality, CO2 concentrations, temperature and relative humidity and safety issues that may be important drawbacks for naturally ventilated schools. The aim of this paper is to develop a conceptual understanding of methods that can be implemented to assess the effectiveness of naturally ventilated classrooms in Gauteng, South Africa. A theoretical concept with an embedded practical methodology have been proposed for the research programme to investigate the relationship between ventilation rates and learning in schools in Gauteng , a province in South Africa. It is important that existing and future school buildings must include adequate outdoor ventilation, control of moisture, and avoidance of indoor exposures to microbiologic and chemical substances considered likely to have adverse effects in South Africa. Adequate ventilation in classrooms is necessary to reduce and/or eradicate the transmission of indoor pollutants.

Knowledge and perception of Ghanaian cocoa farmers on mirid control and their willingness to use forecasting systems

Annual losses of cocoa in Ghana to mirids are significant. Therefore, accurate timing of insecticide application is critical to enhance yields. However, cocoa farmers often lack information on the expected mirid population for each season to enable them to optimise pesticide use. This study assessed farmers’ knowledge and perceptions of mirid control and their willingness to use forecasting systems informing them of expected mirid peaks and time of application of pesticides. A total of 280 farmers were interviewed in the Eastern and Ashanti regions of Ghana with a structured open and closed ended questionnaire. Most farmers (87%) considered mirids as the most important insect pest on cocoa with 47% of them attributing 30-40% annual crop loss to mirid damage. There was wide variation in the timing of insecticide application as a result of farmers using different sources of information to guide the start of application. The majority of farmers (56%) do not have access to information on the type, frequency and timing of insecticides to use. However, respondents who are members of farmer groups had better access to such information. Extension officers were the preferred channel for information transfer to farmers with 72% of farmers preferring them to other available methods of communication. Almost all the respondents (99%) saw the need for a comprehensive forecasting system to help farmers manage cocoa mirids. The importance of accurate timing for mirid control based on forecasted information to farmer groups and extension officers was discussed.