Developing an efficient and reliable dry powder inhaler for pulmonary drug delivery : a review for multidisciplinary researchers

Pulmonary drug delivery is the focus of much research and development because of its great potential to produce maximum therapeutic benefit. Among the available options the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse number of diseases. However, as drug delivery from a DPI involves a complicated set of physical processes and the integration of drug formulations, device design and patient usage, the engineering development of this medical technology is proving to be a great challenge. Currently there is large range of devices that are either available on the market or under development, however, none exhibit superior clinical efficacy. A major concern is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs. The extent of variability depends on the drug formulation, the device design and the patient’s inhalation profile. This article reviews recent advances in DPI technology and presents the key factors which motivate and constrain the successful engineering of a universal, patient-independent DPI that is capable of efficient, reliable and repeatable drug delivery. A strong emphasis is placed on the physical processes of drug powder aerosolisation, deagglomeration, and dispersion and on the engineering of formulations and inhalers that can optimise these processes.

A hybrid model for studying spatial aspects of infectious diseases

We consider a hybrid model, created by coupling a continuum and an agent-based model of infectious disease. The framework of the hybrid model provides a mechanism to study the spread of infection at both the individual and population levels. This approach captures the stochastic spatial heterogeneity at the individual level, which is directly related to deterministic population level properties. This facilitates the study of spatial aspects of the epidemic process. A spatial analysis, involving counting the number of infectious agents in equally sized bins, reveals when the spatial domain is nonhomogeneous.

Managing distraction and attention in diverse cohorts : 21st century challenges to law student engagement

It is imperative that we consider the use of current and emerging technologies in terms of the nature of our learners, the physical environment of the lecture theatre, and how technology may help to support appropriate pedagogies that facilitate the capturing of student attention in active engaging learning experiences. It is argued that a re-evaluation of pedagogy is required to address the tech-savy traits of the 21st century learner and the extent to which their mobile devices are capable of not only distracting them from learning but also enhancing face-to-face learning experiences.

Taxing charities : reform without reason?

The proposal to tax the unrelated business income of charitable organisations was announced in the 2011 budget, but the course of events has overtaken the stated policy rationale. We identify and discuss the policy for the imposition of the new tax and demonstrate that the measure is unnecessary given a recent judgement by the High Court, establishment of a new charity regulator and a better understanding of the applicable tax theory.

Tactically-driven nonmonotone travelling waves

Models of cell invasion incorporating directed cell movement up a gradient of an external substance and carrying capacity-limited proliferation give rise to travelling wave solutions. Travelling wave profiles with various shapes, including smooth monotonically decreasing, shock-fronted monotonically decreasing and shock-fronted nonmonotone shapes, have been reported previously in the literature. The existence of tacticallydriven shock-fronted nonmonotone travelling wave solutions is analysed for the first time. We develop a necessary condition for nonmonotone shock-fronted solutions. This condition shows that some of the previously reported shock-fronted nonmonotone solutions are genuine while others are a consequence of numerical error. Our results demonstrate that, for certain conditions, travelling wave solutions can be either smooth and monotone, smooth and nonmonotone or discontinuous and nonmonotone. These different shapes correspond to different invasion speeds. A necessary and sufficient condition for the travelling wave with minimum wave speed to be nonmonotone is presented. Several common forms of the tactic sensitivity function have the potential to satisfy the newly developed condition for nonmonotone shock-fronted solutions developed in this work.

β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice

Objective The spondylarthritides (SpA), including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of the large peripheral and axial joints, eyes, skin, ileum, and colon. Genetic studies reveal common candidate genes for AS, PsA, and Crohn's disease, including IL23R, IL12B, STAT3, and CARD9, all of which are associated with interleukin-23 (IL-23) signaling downstream of the dectin 1 β-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17–dependent inflammatory arthritis developed after dectin 1–mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-β-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process. Methods SKG mice and control BALB/c mice were injected once with curdlan or mannan. Arthritis was scored weekly, and organs were assessed for pathologic features. Anti–IL-23 monoclonal antibodies were injected into curdlan-treated SKG mice. CD4+ T cells were transferred from curdlan-treated mice to SCID mice, and sera were analyzed for autoantibodies. Results After systemic injection of curdlan, SKG mice developed enthesitis, wrist, ankle, and sacroiliac joint arthritis, dactylitis, plantar fasciitis, vertebral inflammation, ileitis resembling Crohn's disease, and unilateral uveitis. Mannan triggered spondylitis and arthritis. Arthritis and spondylitis were T cell– and IL-23–dependent and were transferable to SCID recipients with CD4+ T cells. SpA was associated with collagen- and proteoglycan-specific autoantibodies. Conclusion Our findings indicate that the SKG ZAP-70W163C mutation predisposes BALB/c mice to SpA, resulting from innate and adaptive autoimmunity, after systemic β-glucan or mannan exposure.

The Socratic classroom : reflective thinking through collaborative inquiry

This book was written to serve two functions. First it is an exploration of what I have called Socratic pedagogy, a collaborative inquiry-based approach to teaching and learning suitable not only to formal educational settings such as the school classroom but to all educational settings. The term is intended to capture a variety of philosophical approaches to classroom practice that could broadly be described Socratic in form. The term ‘philosophy in schools’ is ambiguous and could refer to teaching university style philosophy to high school students or to the teaching of philosophy and logic or critical reasoning in senior years of high school. It is also used to describe the teaching of philosophy in schools generally. In the early and middle phases of schooling the term philosophy for children is often used. But this too is ambiguous as the name was adopted from Matthew Lipman’s Philosophy for Children curriculum that he and his colleagues at the Institute for the Advancement of Philosophy for Children developed. In Britain the term ‘philosophy with children’ is sometimes employed to mark two methods of teaching that have Socratic roots but have distinct differences, namely Philosophy for Children and Socratic Dialogue developed by Leonard Nelson. The use of the term Socratic pedagogy and its companion term Socratic classroom (to refer to the kind of classroom that employs Socratic teaching) avoids the problem of distinguishing between various approaches to philosophical inquiry in the Socratic tradition but also separates it from the ‘study of philosophy’, such as university style philosophy or other approaches which place little or no emphasis on collaborative inquiry based teaching and learning. The second function builds from the first. It is to develop an effective framework for understanding the relationship between what I call the generative, evaluative and connective aspects of communal dialogue, which I think are necessary to the Socratic notion of inquiry. In doing so it is hoped that this book offers some way to show how philosophy as inquiry can contribute to educational theory and practice, while also demonstrating how it can be an effective way to approach teaching and learning. This has meant striking a balance between speaking to philosophers and to teachers and educators together, with the view that both see the virtues of such a project. In the strictest sense this book is not philosophy of education, insofar as its chief focus is not on the analysis of concepts or formulation of definitions specific to education with the aim of formulating directives that guide educational practice. It relinquishes the role of philosopher as ‘spectator’, to one of philosopher ‘immersed in matter’ – in this case philosophical issues in education, specifically those related to philosophical inquiry, pedagogy and classroom practice. Put another way, it is a book about philosophical education.

Upwave cities, creative cities : the case of London

The saddest book on cities I have read in a long time is The Lost City of Stoke-on-Trent by Matthew Rice (2010). Rice, who is married to the pottery owner Emma Bridgewater, charts the long decline of the potteries since the 1970s, when many brands closed local potteries to move overseas to Indonesia. There are now only a dozen or so potteries left in Stoke and many jobs that once were there have simply vanished. Yet at one time, Stoke was a place of great wealth creation, innovation and industriousness. The lesson is that once a local economy loses its dynamism, the place itself stagnates and may even die. Stoke is to the UK what Detroit is to the USA. Rice also shows that successive attempts at urban renewal have largely failed to make any impact in reversing Stoke’s declining fortunes. Economic stagnation and decline occurs in real places, leaving multiple economic, social and cultural problems in its wake. Over a period of years, local communities and residents gradually grow poorer, as wealth leaks away to other places.

Revision total hip replacement using the cement-in-cement technique for the acetabular component : technique and results for 60 hips

The technique of femoral cement-in-cement revision is well established, but there are no previous series reporting its use on the acetabular side at the time of revision total hip arthroplasty. We describe the surgical technique and report the outcome of 60 consecutive cement-in-cement revisions of the acetabular component at a mean follow-up of 8.5 years (range 5-12 years). All had a radiologically and clinically well fixed acetabular cement mantle at the time of revision. 29 patients died. No case was lost to follow-up. The 2 most common indications for acetabular revision were recurrent dislocation (77%) and to compliment a femoral revision (20%). There were 2 cases of aseptic cup loosening (3.3%) requiring re-revision. No other hip was clinically or radiologically loose (96.7%) at latest follow-up. One case was re-revised for infection, 4 for recurrent dislocation and 1 for disarticulation of a constrained component. At 5 years, the Kaplan-Meier survival rate was 100% for aseptic loosening and 92.2% (95% CI; 84.8-99.6%) with revision for all causes as the endpoint. These results support the use of the cement-in-cement revision technique in appropriate cases on the acetabular side. Theoretical advantages include preservation of bone stock, reduced operating time, reduced risk of complications and durable fixation.

Preface to special issue on digital human modelling for vehicle design and manufacturing

The automotive industry has been the focus of digital human modeling (DHM) research and application for many years. In the highly competitive marketplace for personal transportation, the desire to improve the customer’s experience has driven extensive research in both the physical and cognitive interaction between the vehicle and its occupants. Human models provide vehicle designers with tools to view and analyze product interactions before the first prototypes are built, potentially improving the design while reducing cost and development time. The focus of DHM research and applications began with prediction and representation of static postures for purposes of driver workstation layout, including assessments of seat adjustment ranges and exterior vision. Now DHMs are used for seat design and assessment of driver reach and ingress/egress. DHMs and related simulation tools are expanding into the cognitive domain, with computational models of perception and motion, and into the dynamic domain with models of physical responses to ride and vibration. Moreover, DHMs are now widely used to analyze the ergonomics of vehicle assembly tasks. In this case, the analysis aims to determine whether workers can be expected to complete the tasks safely and with good quality. This preface provides a review of the literature to provide context for the nine new papers presented in this special issue.

Analysis of Cone-Beam CT using prior information

Treatment plans for conformal radiotherapy are based on an initial CT scan. The aim is to deliver the prescribed dose to the tumour, while minimising exposure to nearby organs. Recent advances make it possible to also obtain a Cone-Beam CT (CBCT) scan, once the patient has been positioned for treatment. A statistical model will be developed to compare these CBCT scans with the initial CT scan. Changes in the size, shape and position of the tumour and organs will be detected and quantified. Some progress has already been made in segmentation of prostate CBCT scans [1],[2],[3]. However, none of the existing approaches have taken full advantage of the prior information that is available. The planning CT scan is expertly annotated with contours of the tumour and nearby sensitive objects. This data is specific to the individual patient and can be viewed as a snapshot of spatial information at a point in time. There is an abundance of studies in the radiotherapy literature that describe the amount of variation in the relevant organs between treatments. The findings from these studies can form a basis for estimating the degree of uncertainty. All of this information can be incorporated as an informative prior into a Bayesian statistical model. This model will be developed using scans of CT phantoms, which are objects with known geometry. Thus, the accuracy of the model can be evaluated objectively. This will also enable comparison between alternative models.

Velocity jump processes with proliferation

Cell invasion involves a population of cells that migrate along a substrate and proliferate to a carrying capacity density. These two processes, combined, lead to invasion fronts that move into unoccupied tissues. Traditional modelling approaches based on reaction–diffusion equations cannot incorporate individual–level observations of cell velocity, as information propagates with infinite velocity according to these parabolic models. In contrast, velocity jump processes allow us to explicitly incorporate individual–level observations of cell velocity, thus providing an alternative framework for modelling cell invasion. Here, we introduce proliferation into a standard velocity–jump process and show that the standard model does not support invasion fronts. Instead, we find that crowding effects must be explicitly incorporated into a proliferative velocity–jump process before invasion fronts can be observed. Our observations are supported by numerical and analytical solutions of a novel coupled system of partial differential equations, including travelling wave solutions, and associated random walk simulations.

GLBTI police liaison services : a critical analysis of existing literature

GLBTI (gay, lesbian, bisexual, transgender, intersex) police liaison programs have been an important part of policing these communities for a number of decades now. In fact, this model appears to dominate approaches as the preferred way to manage relationships between GLBTI communities and police. Interestingly, while this model dominates, research on the effectiveness of this model, and the services that align with it, is limited. To date, only few studies have asked critical questions about the effectiveness of GLBTI police liaison services. For instance, we know that over 70% of GLBTI communities are aware of police liaison services, but only 4% of those victimised access them (Berman & Robinson, 2010). This paper critically examines existing literature about GLBTI police liaison services to demonstrate key themes and omissions. It argues that police liaison services as a preferred model has been taken for granted as the correct way of engaging with GLBTI communities in ways that may exclude other forms of engagement, and suggests that further research into these liaison programs is necessary if the relationships between GLBTI communities and the police are to be strengthened.