Predicting pMDI formulation thermophysical properties using activity coefficient models

The Kigali amendment to Montreal protocol sets the timetable for phasing out of pMDI propellants HFA134a and HFA227ea, creating a requirement for green propellants to take their place. To assist this transition, accurate prediction of thermophysical properties that control aerosol generation of new formulations is crucial. A relevant challenge is how to predict property data such as saturated vapour pressure, surface tension and viscosity of propellant/excipient/drug mixtures using the smallest possible programme of physical testing. It is proposed to use a thermodynamic framework based on activity coefficients to model intermolecular forces between constituents, which are known to control multi-component thermophysical property behaviour. It is proposed to use the UNIFAC method, which is based on detailed physical understanding of molecular functional groups and their interactions, with the ability to capture azeotropic behaviour. Surface tension, viscosity and vapour pressure measurements of mixtures of HFA134a with ethanol at 20°C have been studied to validate the technique. Utilizing UNIFAC parameter fitting to the experimental dataset with non-linear least-squares optimization, a root mean square deviation (RMSD) of 7% in predicted surface tension, 6% in predicted viscosity and 2% in predicted vapour pressure was obtained. Previously unavailable UNIFAC interaction parameters for HFA-alcohol mixtures were created. The capability is highly versatile, accepting various thermophysical property data and giving good agreement with measured values for existing formulation mixtures. The framework can be readily applied to mixtures of green propellants such as HFA152a to extend experimental data when available and support insights into thermophysical properties and aerosol generation

The year in cardiology: arrhythmias and pacing.

During this last year, there has been much progress with regard to anticoagulant and ablation therapy for atrial fibrillation (AF). Apart from recently issued European Society of Cardiology Guidelines for the management of patients with supraventricular arrhythmias, there has been little progress in research in this field. Ventricular arrhythmias and device therapy have seen modest progress

A thermodynamic framework to predict thermophysical properties that control pMDI aerosol generation

Activity coefficient models are introduced to provide a thermodynamic framework for simultaneously predicting multiple thermophysical properties of relevance to pressurized metered dose inhaler (pMDI) aerosol formation. The UNIFAC and UNIQUAC models are discussed in the context of calculation of saturated vapor pressure, surface tension and liquid viscosity using molecule and functional group interaction parameters. New interaction parameters are generated and presented for HFA134a/ethanol mixtures using experimental data for saturated vapor pressure, surface tension and viscosity. The UNIFAC model is shown to give adequate predictivity and can be used when no experimental data is available. Better predictions were obtained with the UNIQUAC model, which is most useful when high-quality measurement data are obtained. The use of these models for flexible thermophysical property prediction of low-global warming potential (GWP) formulations is discussed, with potential developments to improve model fits and better utilize the experimental data

Validity in market research Practice: `New' is not always `improved'

Market research suppliers want to provide a differentiated product or service offering to their clients. However, the frequent need to appear 'new' results in adaptation of research to different contexts. This has consequences for validity. In this paper we make the case for tempering the existing enthusiasm for constant 'innovation' in market research methodologies. In particular, we argue that unfettered adaptation can lead to the generation of invalid findings. We demonstrate some methods of how invalid results can develop. Finally we explain current concepts of 'validity' and provide an innovative way of showing the relationship between the dozen or more varieties of validity that are commonly used in the literature(s). This paper aims to remind practitioners and academics alike, that concepts of validity are important and that there is no point in having a perfectly reliable, but completely invalid, measurement tool

Building a full-size glider

The building and flying of a glider is possible for anyone who can use a few basic tools. This report presents some plans and techniques for building your own glider

Managing Engineering Talent: Unique Challenges to Optimize the Best and Brightest

Most engineers are bright, hard-working, reliable, and prefer to avoid conflict. An engineering curriculum tends to self-select these characteristics. By most standards, you would expect workers exhibiting these traits to require minimal supervision. But is this true? Is this how most current engineering managers lead? Looking at some current theories on leadership combined with personal anecdotes, this presentation will look at some common misconceptions about leading engineers

The Programming Power of the Placenta.

Size at birth is a critical determinant of life expectancy, and is dependent primarily on the placental supply of nutrients. However, the placenta is not just a passive organ for the materno-fetal transfer of nutrients and oxygen. Studies show that the placenta can adapt morphologically and functionally to optimize substrate supply, and thus fetal growth, under adverse intrauterine conditions. These adaptations help meet the fetal drive for growth, and their effectiveness will determine the amount and relative proportions of specific metabolic substrates supplied to the fetus at different stages of development. This flow of nutrients will ultimately program physiological systems at the gene, cell, tissue, organ, and system levels, and inadequacies can cause permanent structural and functional changes that lead to overt disease, particularly with increasing age. This review examines the environmental regulation of the placental phenotype with particular emphasis on the impact of maternal nutritional challenges and oxygen scarcity in mice, rats and guinea pigs. It also focuses on the effects of such conditions on fetal growth and the developmental programming of disease postnatally. A challenge for future research is to link placental structure and function with clinical phenotypes in the offspring.This is the final version of the article. It first appeared from Frontiers via https://doi.org/10.3389/fphys.2016.0003

Near to One's Heart: The Intimate Relationship Between the Placenta and Fetal Heart.

The development of the fetal heart is exquisitely controlled by a multitude of factors, ranging from humoral to mechanical forces. The gatekeeper regulating many of these factors is the placenta, an external fetal organ. As such, resistance within the placental vascular bed has a direct influence on the fetal circulation and therefore, the developing heart. In addition, the placenta serves as the interface between the mother and fetus, controlling substrate exchange and release of hormones into both circulations. The intricate relationship between the placenta and fetal heart is appreciated in instances of clinical placental pathology. Abnormal umbilical cord insertion is associated with congenital heart defects. Likewise, twin-to-twin transfusion syndrome, where monochorionic twins have unequal sharing of their placenta due to inter-twin vascular anastomoses, can result in cardiac remodeling and dysfunction in both fetuses. Moreover, epidemiological studies have suggested a link between placental phenotypic traits and increased risk of cardiovascular disease in adult life. To date, the mechanistic basis of the relationships between the placenta, fetal heart development and later risk of cardiac dysfunction have not been fully elucidated. However, studies using environmental exposures and gene manipulations in experimental animals are providing insights into the pathways involved. Likewise, surgical instrumentation of the maternal and fetal circulations in large animal species has enabled the manipulation of specific humoral and mechanical factors to investigate their roles in fetal cardiac development. This review will focus on such studies and what is known to date about the link between the placenta and heart development

Long-range gravitational-like interaction in a neutral atomic cold gas

A quasi-resonant laser induces a long-range attractive force within a cloud of cold atoms. We take advantage of this force to build in the laboratory a system of particles with a one-dimensional gravitational-like interaction, at a fluid level of modeling. We give experimental evidences of such an interaction in a cold Strontium gas, studying the density profile of the cloud, its size as a function of the number of atoms, and its breathing oscillations.Comment: 4 pages, 4 figures. Published in PRA 87, 013401 (2013