Microbicide Vaginal Rings: Technological Challenges and Clinical Development

Vaginal rings (VRs) are flexible, torus-shaped, polymeric devices designed to sustain delivery of pharmaceutical drugs to the vagina for clinical benefit. Following first report in a 1970 patent application, several steroid-releasing VR products have since been marketed for use in hormone replacement therapy and contraception. Since 2002, there has been growing interest in the use of VR technology for delivery of drugs that can reduce the risk of sexual acquisition of human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Although no vaginally-administered product has yet been approved for HIV reduction/prevention, extensive research efforts are continuing and a number of VR devices offering sustained release of so-called ‘HIV microbicide’ compounds are currently being evaluated in late-stage clinical studies. This review article provides an overview of the published scientific literature within this important field of research, focusing primarily on articles published within peer-reviewed journal publications. Many important aspects of microbicide-releasing VR technology are discussed, with a particular emphasis on the technological, manufacturing and clinical challenges that have emerged in recent years.

Sustainable non-automotive vehicles: The simulation challenges

Simulation is a well-established and effective approach to the development of fuel-efficient and low-emissions vehicles in both on-highway and off-highway applications.

The simulation of on-highway automotive vehicles is widely reported in literature, whereas research relating to non-automotive and off-highway vehicles is relatively sparse. This review paper focuses on the challenges of simulating such vehicles and discusses the differences in the approach to drive cycle testing and experimental validation of vehicle simulations. In particular, an inner-city diesel-electric hybrid bus and an ICE (Internal Combustion Engine) powered forklift truck will be used as case studies.

Computer prediction of fuel consumption and emissions of automotive vehicles on standardised drive cycles is well-established and commercial software packages such as AVL CRUISE have been specifically developed for this purpose. The vehicles considered in this review paper present new challenges from both the simulation and drive-cycle testing perspectives. For example, in the case of the forklift truck, the drive cycles involve reversing elements, variable mass, lifting operations, and do not specify a precise velocity-time profile. In particular, the difficulties associated with the prediction of productivity, i.e. the maximum rate of completing a series of defined operations, are discussed. In the case of the hybrid bus, the standardised drive cycles are unrepresentative of real-life use and alternative approaches are required in the development of efficient and low-emission vehicles.

Two simulation approaches are reviewed: the adaptation of a standard automotive vehicle simulation package, and the development of bespoke models using packages such as MATLAB/Simulink.

Handbook of Disabled Children's Childhoods: Building Understandings: Child, Youth, Family and Disability. Palgrave Macmillan:Disabled Children in Out-of-Home Care: Issues and Challenges for Practice Kelly, B., Sandra, D. & Winter, K. 2016

This chapter provides an overview of some of the key findings from a large mixed methods study regarding disabled children in care in Northern Ireland

The OpenPMU Project: Challenges and perspectives:Challenges and Perspectives

The OpenPMU project is a platform for the development of Synchrophasor measurement technology, Phasor Measurement Units (PMU), in an open source manner. The project has now been operating for a number of years and has seen increased adoption at Universities and interest from electrical utilities. The OpenPMU device has recently been tested against the IEEE C37.118 standard and shown to operate within the specification. This paper discusses the OpenPMU project from the perspective of the past two years of experience and evaluates successes and opportunities for improvements in both the OpenPMU device and the philosophy of the design.

Minimising harm from alcohol misuse: Challenges to the development of effective policy

Successive substance misuse strategies in Northern Ireland and elsewhere have
been underpinned by the goal of minimising the harm accruing from the use of alcohol and other drugs. However, what it means for a person’s alcohol use to cause harm is an evolving concept. As the understanding of harm changes, the type of evidence needed to estimate the scale of harm and to evaluate the success of a given initiative changes also.
This paper does three things. We first highlight a recent model by Laslett and
colleagues for estimating the harm of one individual’s alcohol use to other individuals, the centrepiece of a report to the Alcohol Education and Research Foundation (AERF) in 2010. This model has been hugely influential in identifying areas where harms from alcohol use accrue and in attempting to quantify those harms (e.g. the cost of injuries inflicted during intoxication). We suggest three ways in which this model could be improved by accounting for: (a) the influence of one individual’s drinking on the drinking behaviour of their peers; (b) the level of use which triggers a given harm; and (c) the degree of time-lag in each of
the domains of harm.
Secondly, we explore specific challenges to developing effective policy on
adolescents’ drinking behaviours, drawing on research which specifically elicits the perspectives of young people on why they drink.
Thirdly, we examine the relative harms of allowing moderate levels of drinking
among mid-adolescents versus promoting zero use up until late adolescence.

Challenges in mercury speciation and fractionation in soil and sediment

This investigation focused on the development, test and validation of methodologies for mercury fractionation and speciation in soil and sediment. After an exhaustive review of the literature, several methods were chosen and tested in well characterised soil and sediment samples. Sequential extraction procedures that divide mercury fractions according to their mobility and potential availability in the environment were investigated. The efficiency of different solvents for fractionation of mercury was evaluated, as well as the adequacy of different analytical instruments for quantification of mercury in the extracts. Kinetic experiments to establish the equilibrium time for mercury release from soil or sediment were also performed. It was found that in the studied areas, only a very small percentage of mercury is present as mobile species and that mobility is associated to higher aluminium and manganese contents, and that high contents of organic matter and sulfur result in mercury tightly bound to the matrix. Sandy soils tend to release mercury faster that clayey soils, and therefore, texture of soil or sediment has a strong influence on the mobility of mercury. It was also understood that analytical techniques for quantification of mercury need to be further developed, with lower quantification limits, particularly for mercury quantification of less concentrated fractions: water-soluble e exchangeable. Although the results provided a better understanding of the distribution of mercury in the sample, the complexity of the procedure limits its applicability and robustness. A proficiency-testing scheme targeting total mercury determination in soil, sediment, fish and human hair was organised in order to evaluate the consistency of results obtained by different laboratories, applying their routine methods to the same test samples. Additionally, single extractions by 1 mol L-1 ammonium acetate solution, 0.1 mol L-1 HCl and 0.1 mol L-1 CaCl2, as well as extraction of the organometallic fraction were proposed for soil; the last was also suggested for sediment and fish. This study was important to update the knowledge on analytical techniques that are being used for mercury quantification, the associated problems and sources of error, and to improve and standardize mercury extraction techniques, as well as to implement effective strategies for quality control in mercury determination. A different, “non chemical-like” method for mercury species identification was developed, optimised and validated, based on the thermo-desorption of the different mercury species. Compared to conventional extraction procedures, this method has advantages: it requires little to no sample treatment; a complete identification of species present is obtained in less than two hours; mercury losses are almost neglectable; can be considered “clean”, as no residues are produced; the worldwide comparison of results obtained is easier and reliable, an important step towards the validation of the method. Therefore, the main deliverables of this PhD thesis are an improved knowledge on analytical procedures for identification and quantification of mercury species in soils and sediments, as well as a better understanding of the factors controlling the behaviour of mercury in these matrices.

Dealing with uncertainty: challenges and possibilities for the early childhood profession

In many countries, strategies to further develop services and institutions for the education and care of young children are linked to a discourse on professionalism. Ambitious policy goals, it is argued, can only be achieved by a skilled and qualified workforce whose practice is guided by a professional body of knowledge. This article argues that the prevailing conceptualisation of the early childhood professional is constructed out of a particular, hierarchical mode of producing and applying expert knowledge that is not necessarily appropriate to professional practice in the field of early childhood education. However, it is highly effective and contributes to forming a professional habitus that contradicts the relational core of early childhood practice. Drawing on the conceptual framework of hermeneutics, the article explores an alternative paradigm of a relational, systemic professionalism that embraces openness and uncertainty, and encourages co‐construction of professional knowledges and practices. Research, in this frame of thinking, is understood as a dialogic activity of asking critical questions and creating understandings across differences, rather than producing evidence to direct practice.