Approaches to Understanding the Milling Outcomes of Pharmaceutical Polymorphs, Salts and Cocrystals. The Effect of Different Milling Techniques (Ball and Jet) on the Physical Nature and Surface Energetics of Different Forms of Indomethacin and Sulfathiazole to Include Computational Insights.

The process of milling drugs to obtain samples with a desirable particle size range has been widely used in the pharmaceutical industry, especially for the production of drugs for inhalation. However by subjecting materials to milling techniques surfaces may become thermodynamically activated which may in turn lead to formation of amorphous material. Polymorphic conversions have also been noted after milling of certain materials. Salt and cocrystal formation is a good way of enhancing the properties of an API but little or no work has been published which investigates the stability of these entities when subjected to milling. Different milling techniques (ball and jet) and temperatures (ambient and cryogenic) were used to investigate the milling behaviour of polymorphs, salts and cocrystals. All materials were analysed by XRPD and DSC to investigate any physical changes, i.e. changes in melting point and by inverse gas chromatography (IGC) to investigate whether any changes in the surface energetics occurred as a result of milling. Another aim of this thesis was to see if it was possible to predict the milling behaviour of polymorphs by calculating the attachment energies of the different crystal facets using Materials Studio 4.0. These results were compared to the IGC data to see if the predicted surface changes had occurred. The data collected in this study showed that different milling techniques can have a different effect on the same material. For example ball milling at ambient temperature and jet micronisation of the SFZ tosylate salt caused a notable increase in the melting point of the material whereas ball milling at cryogenic temperatures did not cause this to happen. The IGC data collected for this form also showed a contrast between cryomilling and the other two techniques. The study also showed that the formation of salts and cocrystals does not necessarily offer any increased stability in terms of physical properties or surface energetics. Changes in melting point were observed for the SFZ tosylate salt and the IMC:Benzamide cocrystal. Changes in the specific surface energies were also observed indicating that the nature of the surfaces was also changing. The materials which appeared to be affected the least were the two stable polymorphs, gamma IMC and SFZ III. The computational approach used has many limitations. The software does not allow for conversion to the amorphous form or polymorphic conversions. Such conversions were seen to occur, particularly for the metastable polymorphs used, meaning that this computational approach may only be suitable for stable polymorphs

‘Shifting between the internal and external’: Psychoanalytic ways of working with children in local authority care

This thesis seeks to explore psychoanalytic ways of working with children in local authority care. Despite evidence suggesting psychoanalytic psychotherapy is used widely in routine clinical practice in the UK and may be helpful for children who experienced early attachment trauma, there is little research examining its use with these children. Study 1 aimed to identify current models of working with looked after and adopted children amongst UK psychoanalytic child psychotherapists. A survey of child psychotherapists (n=215) examined a range of activities, including assessment, therapy, work with foster carers/adoptive parents, and consultation to the professional network. Respondents placed emphasis on work with professionals and foster carers, seeing this as an area of development for services. Study 2 aimed to explore how child psychotherapists understood their work as consultant to the professional network, and what they saw as particular to the psychoanalytic approach. Thematic analysis of in-depth interviews (n=9) identified that participants experienced various tensions they held within themselves in their role, particularly around wanting to offer a network-led approach, when professionals often asked them to provide therapy. Study 3 aimed to understand how child psychotherapists function within a specialist children’s social care setting, including how they positioned themselves in a multi-disciplinary Child and Adolescent Mental Health Service (CAMHS) and a multi-agency setting. Grounded theory analysis of an ethnographic case study identified that the child psychotherapists balanced three elements of their professional identity in this role: a discipline-specific identity; CAMHS team identity; and professional network member identity. To be effective in their role, the child psychotherapists needed to integrate the elements of their professional identity. Collectively, the findings have implications for understanding the role of UK child psychotherapists working with children in local authority care; particularly the significance, but also complexity, of work with the professional network around the child

Analysing trade-offs and synergies between SDGs for urban development, food security and poverty alleviation in rapidly changing peri-urban areas: a tool to support inclusive urban planning

Transitional peri-urban contexts are frontiers for sustainable development where land-use change involves negotiation and contestation between diverse interest groups. Multiple, complex trade-offs between outcomes emerge which have both negative and positive impacts on progress towards achieving Sustainable Development Goals (SDGs). These trade-offs are often overlooked in policy and planning processes which depend on top-down expert perspectives and rely on course grain aggregate data which does not reflect complex peri-urban dynamics or the rapid pace of change. Tools are required to address this gap, integrate data from diverse perspectives and inform more inclusive planning processes. In this paper, we draw on a reinterpretation of empirical data concerned with land-use change and multiple dimensions of food security from the city of Wuhan in China to illustrate some of the complex trade-offs between SDG goals that tend to be overlooked with current planning approaches. We then describe the development of an interactive web-based tool that implements deep learning methods for fine-grained land-use classification of high-resolution remote sensing imagery and integrates this with a flexible method for rapid trade-off analysis of land-use change scenarios. The development and potential use of the tool are illustrated using data from the Wuhan case study example. This tool has the potential to support participatory planning processes by providing a platform for multiple stakeholders to explore the implications of planning decisions and land-use policies. Used alongside other planning, engagement and ecosystem service mapping tools it can help to reveal invisible trade-offs and foreground the perspectives of diverse stakeholders. This is vital for building approaches which recognise how trade-offs between the achievement of SDGs can be influenced by development interventions

Online randomised controlled trial to evaluate the clinical and cost-effectiveness of a web-based peer-supported self-management intervention for relatives of people with psychosis or bipolar disorder: Relatives’ Education And Coping Toolkit (REACT)

Background Relatives caring for people with severe mental health problems find information and emotional support hard to access. Online support for self-management offers a potential solution. Objective To determine the clinical and cost-effectiveness of an online supported self-management tool for relatives, the Relatives’ Education And Coping Toolkit (REACT). Design A primarily online, single-blind, randomised controlled trial, comparing REACT plus a resource directory (RD) and treatment as usual (TAU), against the RD and TAU only, by measuring user distress and other wellbeing measures at start, 12 and 24 weeks. Participants 800 relatives across UK, aged 16 or over, with high levels of distress, access to Internet, and actively seeking help. Intervention REACT comprised 12 psychoeducation modules, peer support through a group forum, confidential messaging, and a comprehensive RD of national support. Trained relatives moderated the forum and responded to messages. Main outcome measure Participants’ distress, measured by the General Health Questionnaire (GHQ-28). Results Recruitment was via study website. Various online and offline strategies including social media directed potential participants to the site. Participants were randomised into two groups: REACT plus RD (n=399) or RD only (n=401). Retention at 24 weeks was 75% (REACT n=292; RD-only n=307). Mean GHQ-28 scores fell substantially across both groups over 24 weeks, from mean 40.2, standard deviation (SD) 14.3 to mean 30.5, SD 15.6, with no significant difference between groups (-1.39, 95% CI -3.60–0.83, p=0.22). At 12 weeks GHQ-28 scores were lower in the REACT arm than in RD-only (-2.08, 95% CI -4.14– -0.03, p=0.027), but of likely limited clinical significance. Accounting for missing data, which was associated with higher distress in the REACT arm (0.33, 95% CI -0.27–0.93, p=0.279), in a longitudinal model, there was no significant difference between groups over 24 weeks (-0.56, 95% CI–2.34–1.22, p=0.51). iv REACT cost £142.95 per participant to design and deliver (£62.27 delivery only) against £0.84 for RD-only. Health economic analysis of NHS, health and personal social services outcomes found REACT to have higher costs of £286.77, slightly better GHQ scores (incremental GHQ adjusted for baseline, age and gender: -1.152, 95% CI -3.370–1.065), and slightly lower QALYs than RD-only; none of these differences was statistically significant. Median time spent online was 50.8 minutes for REACT (IQR 12.4–172.1) with no significant association against outcome. Participants reported finding REACT a safe, confidential environment (96%), and feeling supported by the forum (89%) and REACT supporters (86%). No serious adverse events reported. Limitations Predominantly white British female sample; 25% lost to follow-up; dropout in the REACT group was not random. Conclusions An online self-management support toolkit with moderated group forum is acceptable to relatives and, compared to face-to-face programmes, offers inexpensive, safe delivery of NICE-recommended support to engage relatives as peers in care delivery. However, currently, REACT plus RD is no more effective in reducing relatives’ distress than RD-only. Future work Further research in improving the effectiveness of online carer support interventions. Study registration ISRCTN72019945 Funding source NIHR Health Technology Assessment programme (14/49/34)

A multi-source feature-level fusion approach for predicting strip breakage in cold rolling

As an undesired and instantaneous failure in the production of cold-rolled strip products, strip breakage results in yield loss, reduced work speed and further equipment damage. Typically, studies have investigated this failure in a retrospective way focused on root cause analyses, and these causes are proven to be multi-faceted. In order to model the onset of this failure in a predictive manner, an integrated multi-source feature-level approach is proposed in this work. Firstly, by harnessing heterogeneous data across the breakage-relevant processes, blocks of data from different sources are collected to improve the breadth of breakage-centric information and are pre-processed according to its granularity. Afterwards, feature extraction or selection is applied to each block of data separately according to the domain knowledge. Matrices of selected features are concatenated in either flattened or expanded manner for comparison. Finally, fused features are used as inputs for strip breakage prediction using recurrent neural networks (RNNs). An experimental study using real-world data instantaneouseffectiveness of the proposed approach