Slow Release Drug Dissolution Profile Prediction in Pharmaceutical Manufacturing: a Multivariate and Machine Learning Approach

Slow release drugs must be manufactured to meet target specifications with respect to dissolution curve profiles. In this paper we consider the problem of identifying the drivers of dissolution curve variability of a drug from historical manufacturing data. Several data sources are considered: raw material parameters, coating data, loss on drying and pellet size statistics. The methodology employed is to develop predictive models using LASSO, a powerful machine learning algorithm for regression with high-dimensional datasets. LASSO provides sparse solutions facilitating the identification of the most important causes of variability in the drug fabrication process. The proposed methodology is illustrated using manufacturing data for a slow release drug.

Thermodynamics of trajectories of a quantum harmonic oscillator coupled to N baths

We undertake a thorough analysis of the thermodynamics of the trajectories followed by a quantum harmonic oscillator coupled to $N$ dissipative baths by using a new approach to large-deviation theory inspired by phase-space quantum optics. As an illustrative example, we study the archetypal case of a harmonic oscillator coupled to two thermal baths, allowing for a comparison with the analogous classical result. In the low-temperature limit, we find a significant quantum suppression in the rate of work exchanged between the system and each bath. We further show how the presented method is capable of giving analytical results even for the case of a driven harmonic oscillator. Based on that result, we analyse the laser cooling of the motion of a trapped ion or optomechanical system, illustrating how the emission statistics can be controllably altered by the driving force.

Seismic damage detection for a steel braced frame structure

A new approach for global detection of seismic damage in a single-storey steel concentrically braced frame (CBF) structure is presented. The filtered lateral in-plane acceleration response of the CBF structure is integrated twice to provide the lateral in-plane displacement which is used to infer buckling and yielding damage. The level of interstorey drift of the CBF during a seismic excitation allows the yield and buckling of the bracing members to be identified and indirectly detects damage based on exceedance of calculated lateral in-plane displacement limits. A band-pass filter removes noise from the acceleration signal followed by baseline correction being used to reduce the drift in velocity and displacement during numerical integration. This pre-processing results in reliable numerical integration of the frame acceleration that predicts the displacement response accurately when compared to the measured lateral displacement of the CBF structure. Importantly, the structural damage is not assumed through removal of bracing members, rather damage is induced through actual seismic loading. The buckling and yielding displacement threshold limits used to identify damage are demonstrated to accurately identify the initiation of buckling and yielding.

Finding a way: Long term care homes to support dementia

An ageing demographic has increased the number of people with dementia. Although dementia is commonly associated with memory loss, other early symptoms include difficulty with wayfinding. Dementia alters visuo-spatial perception and the processes used to interpret the physical environment. The role of the design of the physical environment for people with dementia has gained increased recognition. Despite this, design for dementia is often overlooked, focusing on issues relating to physical impairment. This paper presents the results of a PhD study and aims to examine the role of the design of the physical environment in supporting wayfinding for people with dementia living in long-term care settings in Northern Ireland. Mixed methods combined the observation of wayfinding walks and conversational style interviews to elicit perspectives and experiences of residents with dementia. The findings aim to promote well-being for those with dementia living in long-term care settings.

Simulating reinforced concrete members. Part 2: displacement-based analyses

A companion paper described the partial-interaction localised properties that require the development of pseudo properties. If the quantification through experimental testing of these pseudo properties could be removed by the use of mechanics-based models, which is the subject of this paper, then this would: (a) substantially reduce the cost of developing new reinforced concrete products by reducing the amount of testing; (b) increase the accuracy of designing existing and novel reinforced concrete members and structures, bearing in mind that experimentally derived pseudo properties are only applicable within the range of the testing from which they were derived; and (c) reduce the cost and increase the accuracy of developing reinforced concrete design rules. This paper deals with the development of pseudo properties and behaviours directly through mechanics, as opposed to experimental testing, and their incorporation into member global simulations. It also addresses the need for a fundamental shift to displacement-based analyses as opposed to strain-based analyses.

Simulating reinforced concrete members. Part 1: partial interaction properties

Reinforced concrete members are extremely complex under loading because of localised deformations in the concrete (cracks, sliding planes) and between the reinforcement and concrete (slip). An ideal model for simulating behaviour of reinforced concrete members should incorporate both global behaviour and the localised behaviours that are seen and measured in practice; these localised behaviours directly affect the global behaviour. Most commonly used models do not directly simulate these localised behaviours that can be seen or measured in real members; instead, they overcome these limitations by using empirically or semi-empirically derived strain-based pseudo properties such as the use of effective flexural rigidities for deflection; plastic hinge lengths for strength and ductility; and energy-based approaches for both concrete softening in compression and concrete softening after tensile cracking to allow for tension stiffening. Most reinforced concrete member experimental testing is associated with deriving these pseudo properties for use in design and analysis, and this component of development is thus costly. The aim of the present research is to reduce this cost substantially. In this paper, localised material behaviours and the mechanisms they induce are described. Their incorporation into reinforced concrete member behaviour without the need for empirically derived pseudo properties is described in a companion paper.

Recycling of demolition waste in Merseyside

There have been considerable developments in Merseyside over the last fifteen years with regards to the commercialisation of recycled demolition aggregate. Liverpool is an urban region that at the time was undergoing regeneration. This required the demolition of old infrastructure. Subsequent reconstruction required new construction materials. A project started in 2001 to investigate the economics, practicalities and technicalities of using recycled demolition aggregates in concrete precast products. It was estimated that if all six demolition contractors around Liverpool worked round the clock (i.e. assuming there was enough feed material) they would still have found it difficult to maintain the required supplies for a single precast factory. Investment in equipment was therefore required to guarantee supply and improve the quality of the recycled demolition aggregate. The market forces and the incentives/drivers for construction companies to adopt sustainable practises have encouraged investment of several million pounds to be made in new recycling plants and has resulted in ‘urban quarries’. This paper describes the developments in recycling of construction and demolition waste over the last decade in Merseyside and shows that recycling is not only sustainable but also profitable.

Landauer’s Principle in Multipartite Open Quantum System Dynamics

We investigate the link between information and thermodynamics embodied by Landauer’s principle in the open dynamics of a multipartite quantum system. Such irreversible dynamics is described in terms of a collisional model with a finite temperature reservoir. We demonstrate that Landauer’s principle holds, for such a configuration, in a form that involves the flow of heat dissipated into the environment and the rate of change of the entropy of the system. Quite remarkably, such a principle for heat and entropy power can be explicitly linked to the rate of creation of correlations among the elements of the multipartite system and, in turn, the non-Markovian nature of their reduced evolution. Such features are illustrated in two exemplary cases.

Energy and environmental forensic analysis for public buildings.

This paper outlines a forensic method for analysing the energy, environmental and comfort performance of a building. The method has been applied to a recently developed event space in an Irish public building, which was evaluated using on-site field studies, data analysis, building simulation and occupant surveying. The method allows for consideration of both the technological and anthropological aspects of the building in use and for the identification of unsustainable operational practice and emerging problems. The forensic analysis identified energy savings of up to 50%, enabling a more sustainable, lower-energy operational future for the building. The building forensic analysis method presented in this paper is now planned for use in other public and commercial buildings.

Stochastic analysis of seepage under water-retaining structures

This paper investigated the problem of confined flow under dams and water retaining structuresusing stochastic modelling. The approach advocated in the study combined a finite elementsmethod based on the equation governing the dynamics of incompressible fluid flow through aporous medium with a random field generator that generates random hydraulic conductivity basedon lognormal probability distribution. The resulting model was then used to analyse confined flowunder a hydraulic structure. Cases for a structure provided with cutoff wall and when the wall didnot exist were both tested. Various statistical parameters that reflected different degrees ofheterogeneity were examined and the changes in the mean seepage flow, the mean uplift forceand the mean exit gradient observed under the structure were analysed. Results reveal that underheterogeneous conditions, the reduction made by the sheetpile in the uplift force and exit hydraulicgradient may be underestimated when deterministic solutions are used.

Locations of peculiar supernovae as a diagnostic of their origins

We put constraints on the properties of the progenitors of peculiar calcium-rich transients using the distribution of locations within their host galaxies. We confirm that this class of transients do not follow the galaxy stellar mass profile and are more likely to be found in remote locations of their apparent hosts. We test the hypothesis that these transients are from low-metallicity progenitors by comparing their spatial distributions with the predictions of self-consistent cosmological simulations that include star formation and chemical enrichment. We find that while metal-poor stars and our transient sample show a consistent preference for large offsets, metallicity alone cannot explain the extreme cases. Invoking a lower age limit on the progenitor helps to improve the match, indicating these events may result from a very old metal-poor population. We also investigate the radial distribution of globular cluster systems, and show that they too are consistent with the class of calcium-rich transients. Because photometric upper limits exist for globular clusters for some members of the class, a production mechanism related to the dense environment of globular clusters is not favoured for the calcium-rich events. However, the methods developed in this paper may be used in the future to constrain the effects of low metallicity on radially distant core-collapse events or help establish a correlation with globular clusters for other classes of peculiar explosions.

Supervised Aggregative Feature Extraction for Big Data Time Series Regression

In many applications, and especially those where batch processes are involved, a target scalar output of interest is often dependent on one or more time series of data. With the exponential growth in data logging in modern industries such time series are increasingly available for statistical modeling in soft sensing applications. In order to exploit time series data for predictive modelling, it is necessary to summarise the information they contain as a set of features to use as model regressors. Typically this is done in an unsupervised fashion using simple techniques such as computing statistical moments, principal components or wavelet decompositions, often leading to significant information loss and hence suboptimal predictive models. In this paper, a functional learning paradigm is exploited in a supervised fashion to derive continuous, smooth estimates of time series data (yielding aggregated local information), while simultaneously estimating a continuous shape function yielding optimal predictions. The proposed Supervised Aggregative Feature Extraction (SAFE) methodology can be extended to support nonlinear predictive models by embedding the functional learning framework in a Reproducing Kernel Hilbert Spaces setting. SAFE has a number of attractive features including closed form solution and the ability to explicitly incorporate first and second order derivative information. Using simulation studies and a practical semiconductor manufacturing case study we highlight the strengths of the new methodology with respect to standard unsupervised feature extraction approaches.

Thermodynamics of trajectories and local fluctuation theorems for harmonic quantum networks

We present a general method to undertake a thorough analysis of the thermodynamics of the quantum jump trajectories followed by an arbitrary quantum harmonic network undergoing linear and bilinear dynamics. The approach is based on the phase-space representation of the state of a harmonic network. The large deviation function associated with this system encodes the full counting statistics of exchange and also allows one to deduce for fluctuation theorems obeyed by the dynamics. We illustrate the method showing the validity of a local fluctuation theorem about the exchange of excitations between a restricted part of the environment (i.e., a local bath) and a harmonic network coupled with different schemes.