Integrated design under uncertainty for pharmaceutical processes

in pharmaceutical process development there is frequently a large element of process uncertainty since knowledge of the mechanisms of production and separation is often limited. The overall objective of this thesis is the development of a general methodology which combines process modelling with uncertainty techniques to support the process development of complete integrated sequences. In a structured approach the uncertainty can be managed and improved process performance may be obtained. The major concept of this work is the integration of stochastic methods into a general framework for batch and continuous process models, consisting of two main parts. The first combines systematic modelling procedures with Hammersley sampling based Uncertainty Analysis and a range of sample-based Sensitivity Analysis techniques, used to quantify predicted performance uncertainty and identify key uncertainty contributions. In the second, a stochastic optimisation approach is employed to solve different problems under uncertainty. The methodology was implemented on two case studies. The first study investigated a batch reactor process. Some undesirable performance characteristics were observed when the published nominal optimal isothermal operating policy was implemented in the uncertain system. It was found that a robust operating policy significantly improved the total process time characteristic but not the impurity content and an alternative non-isothermal policy strategy would be a better option. The second study investigated a complete process sequence. As models developed with incoming data, uncertainty in the reaction and crystallisation parameters were critical to the endpoint quality criteria. Expected performance was improved by considering the propagation of uncertainty in the complete process. Four different flowsheets were compared, considering profitability and control tolerance criteria under uncertainty. The case study results indicate the importance in considering uncertainty systematically and quantitatively when conventional modelling techniques are employed. The methodology showed the opportunity to improve process performance potential and provide more realistic information to support pharmaceutical process development

A light-in-flight single-pixel camera for use in the visible and short-wave infrared

This is the final version. Available on open access from the Optical Society of America via the DOI in this recordSingle-pixel cameras reconstruct images from a stream of spatial projection measurements recorded with a single-element detector, which itself has no spatial resolution. This enables the creation of imaging systems that can take advantage of the ultra-fast response times of single-element detectors. Here we present a single-pixel camera with a temporal resolution of 200 ps in the visible and short-wave infrared wavelengths, used here to study the transit time of distinct spatial modes transmitted through few-mode and orbital angular momentum mode conserving optical fiber. Our technique represents a way to study the spatial and temporal characteristics of light propagation in multimode optical fibers, which may find use in optical fiber design and communications.Engineering and Physical Sciences Research Council (EPSRC)European Union Horizon 2020Office of Naval Research (ONR)National Science Foundation (NSF

Cassini observations of the thermal plasma in the vicinity of Saturn's main rings and the F and G rings

The ion mass spectrometer on Cassini detected enhanced ion flux near Saturn's main rings that is consistent with the presence of atomic and molecular oxygen ions in the thermal plasma. The ring "atmosphere'' and "ionosphere'' are likely produced by UV photosputtering of the icy rings and subsequent photoionization of O-2. The identification of the O+ and O-2(+) ions is made using time-of-flight analysis and densities and temperatures are derived from the ion counting data. The ion temperatures over the main rings are a minimum near synchronous orbit and increase with radial distance from Saturn as expected from ion pick up in Saturn's magnetic field. The O-2(+) temperatures provide an estimate of the neutral O-2 temperature over the main rings. The ion mass spectrometer also detected significant O-2(+) outside of the main rings, near the F ring. It is concluded that between the F and G rings, the heavy ion population most likely consists of an admixture of O-2(+) and water group ions O+, OH+, and H2O+

Compressibility of titanosilicate melts

The effect of composition on the relaxed adiabatic bulk modulus (K0) of a range of alkali- and alkaline earth-titanosilicate [X 2 n/n+ TiSiO5 (X=Li, Na, K, Rb, Cs, Ca, Sr, Ba)] melts has been investigated. The relaxed bulk moduli of these melts have been measured using ultrasonic interferometric methods at frequencies of 3, 5 and 7 MHz in the temperature range of 950 to 1600°C (0.02 Pa s < s < 5 Pa s). The bulk moduli of these melts decrease with increasing cation size from Li to Cs and Ca to Ba, and with increasing temperature. The bulk moduli of the Li-, Na-, Ca- and Ba-bearing metasilicate melts decrease with the addition of both TiO2 and SiO2 whereas those of the K-, Rb- and Cs-bearing melts increase. Linear fits to the bulk modulus versus volume fraction of TiO2 do not converge to a common compressibility of the TiO2 component, indicating that the structural role of TiO2 in these melts is dependent on the identity of the cation. This proposition is supported by a number of other property data for these and related melt compositions including heat capacity and density, as well as structural inferences from X-ray absorption spectroscopy (XANES). The compositional dependence of the compressibility of the TiO2 component in these melts explains the difficulty incurred in previous attempts to incorporate TiO2 in calculation schemes for melt compressibility. The empirical relationship KV-4/3 for isostructural materials has been used to evaluate the compressibility-related structural changes occurring in these melts. The alkali metasilicate and disilicate melts are isostructural, independent of the cation. The addition of Ti to the metasilicate composition (i.e. X2TiSiO5), however, results in a series of melts which are not isostructural. The alkaline-earth metasilicate and disilicate compositions are not isostructural, but the addition of Ti to the metasilicate compositions (i.e. XTiSiO5) would appear, on the basis of modulus-volume systematics, to result in the melts becoming isostructural with respect to compressibility

Coping strategies and social support are associated with post-traumatic stress disorder symptoms in Saudi paramedics

Purpose Three main objectives of this study were as follows: (1) To estimate the prevalence rate of post-traumatic stress disordered (PTSD) symptoms among Saudi paramedics, (2) To investigate which types of coping strategies were associated with PTSD symptoms among Saudi paramedics, (3) To explore which sources of social support were associated with PTSD symptoms among Saudi paramedics. Design/methodology/approach Data were collected from 217 paramedics working in the Saudi Red Crescent Authority from September to December 2019. Participants completed questionnaires measuring PTSD symptoms (the Screen of Post-Traumatic Stress Disorders; SPTSD), passive and active coping strategies (Brief COPE Scale; BC), and three forms of social support: support from friends, family and organizational support. Associations between coping strategies, social support and PTSD symptoms were investigated using correlational analyses, hierarchical linear regression and binary logistic regression. Findings 46% of participants experienced one or more PTSD symptom, 28.6% scored above the cut-off for partial PTSD and 17.5% scored above the cut-off for full PTSD. PTSD symptoms were significantly positively correlated with passive coping and negatively associated with both family and friends support. Passive coping was positively associated with a greater risk of meeting criteria for PTSD. Originality/value The current findings suggest that interventions to help reduce PTSD in Saudi paramedics should include strategies to reduce passive coping. Future research is urgently required to help understand the psychological, social and work-related factors that contribute to these high levels of PTSD

Some considerations for the communication of results of air pollution health effects tracking

Communicating effectively and efficiently on air quality and its health impacts is an important but difficult and complex task. It requires careful consideration of the audience one wants to reach, the messages one is trying to present, the venue through which the message will be delivered. The audience, context, technique, and content factors may affect how well it is heard and how appropriately it is interpreted. In this short paper, I describe many of these concerns and provide some suggestions for how best to address them. However, since every audience differs in goals, characteristics, and nature, what is most important is implementing an effective communications program. This program should include frequent two-way communication, repeated and on-going evaluation of how well the audience understands the messages, and consideration of how to improve the delivery

How UK surgeons experience burnout and the link between burnout and patient care: A qualitative investigation

Background and Aims Poor well-being affects the performance of all kinds of workers, including surgeons. This study aimed to answer two questions: (1) how does burnout affect surgeons personally, and what is their burnout experience like? (2) How does burnout affect the care that surgeons provide in the United Kingdom (UK)? Method This study conducted thematic analysis of semi-structured interviews with 14 surgeons recruited from the UK National Health Service (NHS). Result The study found three themes in surgeons’ experiences of burnout: first, burnout is common but frequently not recognised nor understood; second, burnout is a personal crisis; and third, burnout creates vulnerability at work. The study also revealed four themes related to burnout's effect on patient care: first, burnout reduces the quality of surgeon-patient relationships; second, burnout affects patient safety; third, burnout impairs staff relationships; and fourth, burnout makes surgeons less motivated to improve. Conclusion Burnout is common but not well recognised in surgeons. Improving understanding and treatment of burnout could have benefits for both surgeons themselves and the care they provide to patients

Death, dying and informatics: misrepresenting religion on MedLine

BACKGROUND: The globalization of medical science carries for doctors worldwide a correlative duty to deepen their understanding of patients' cultural contexts and religious backgrounds, in order to satisfy each as a unique individual. To become better informed, practitioners may turn to MedLine, but it is unclear whether the information found there is an accurate representation of culture and religion. To test MedLine's representation of this field, we chose the topic of death and dying in the three major monotheistic religions. METHODS: We searched MedLine using PubMed in order to retrieve and thematically analyze full-length scholarly journal papers or case reports dealing with religious traditions and end-of-life care. Our search consisted of a string of words that included the most common denominations of the three religions, the standard heading terms used by the National Reference Center for Bioethics Literature (NRCBL), and the Medical Subject Headings (MeSH) used by the National Library of Medicine. Eligible articles were limited to English-language papers with an abstract. RESULTS: We found that while a bibliographic search in MedLine on this topic produced instant results and some valuable literature, the aggregate reflected a selection bias. American writers were over-represented given the global prevalence of these religious traditions. Denominationally affiliated authors predominated in representing the Christian traditions. The Islamic tradition was under-represented. CONCLUSION: MedLine's capability to identify the most current, reliable and accurate information about purely scientific topics should not be assumed to be the same case when considering the interface of religion, culture and end-of-life care

Sequential Effects in Judgements of Attractiveness: The Influences of Face Race and Sex

In perceptual decision-making, a person’s response on a given trial is influenced by their response on the immediately preceding trial. This sequential effect was initially demonstrated in psychophysical tasks, but has now been found in more complex, real-world judgements. The similarity of the current and previous stimuli determines the nature of the effect, with more similar items producing assimilation in judgements, while less similarity can cause a contrast effect. Previous research found assimilation in ratings of facial attractiveness, and here, we investigated whether this effect is influenced by the social categories of the faces presented. Over three experiments, participants rated the attractiveness of own- (White) and other-race (Chinese) faces of both sexes that appeared successively. Through blocking trials by race (Experiment 1), sex (Experiment 2), or both dimensions (Experiment 3), we could examine how sequential judgements were altered by the salience of different social categories in face sequences. For sequences that varied in sex alone, own-race faces showed significantly less opposite-sex assimilation (male and female faces perceived as dissimilar), while other-race faces showed equal assimilation for opposite- and same-sex sequences (male and female faces were not differentiated). For sequences that varied in race alone, categorisation by race resulted in no opposite-race assimilation for either sex of face (White and Chinese faces perceived as dissimilar). For sequences that varied in both race and sex, same-category assimilation was significantly greater than opposite-category. Our results suggest that the race of a face represents a superordinate category relative to sex. These findings demonstrate the importance of social categories when considering sequential judgements of faces, and also highlight a novel approach for investigating how multiple social dimensions interact during decision-making