A model-based approach towards accelerated process development: A case study on chromatography

Process development is typically associated with lengthy wet-lab experiments for the identification of good candidate setups and operating conditions. In this paper, we present the key features of a model-based approach for the identification and assessment of process design space (DSp), integrating the analysis of process performance and flexibility. The presented approach comprises three main steps: (1) model development & problem formulation, (2) DSp identification, and (3) DSp analysis. We demonstrate how such an approach can be used for the identification of acceptable operating spaces that enable the assessment of different operating points and quantification of process flexibility. The above steps are demonstrated on Protein A chromatographic purification of antibody-based therapeutics used in biopharmaceutical manufacturing.Comment: Pre-print paper under revie

Advanced computational tools to enhance continuous monoclonal antibody production

Leading pharmaceutical companies invest high percentage of their revenue in the improvement of existing technologies used for the production of monoclonal antibodies (mAbs). Recently, there has been a paradigm shift towards the development of continuous/quasi-continuous purification operations, aiming to reduce capital and operational costs [1]. At the moment, however, there are no standardized methods and/or tools that can be used for global control and monitoring of integrated processes. Mathematical models and advanced computational tools can be the key for the development of robust, integrated processes, as they can provide valuable insight in the process dynamics and ensure optimal operation [2]. However, such processes are usually characterized by complex mathematical models and periodic operation profiles that result into computationally expensive solutions and challenge the development of global control methods and tools. In this work, we are presenting a novel approach for the development of advanced controllers towards the intensification of mAb production, considering the fed-batch culturing of GS-NS0 cells and the semi-continuous Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) process [3]. The controller development is realized via the application of a generic framework for the development of advanced control strategies (PAROC) [4] that involves: (i) development of a high-fidelity process model, (ii) approximation of the complex, process model, (iii) design of the multi-parametric controller, (iv) ‘closed-loop’, in-silico validation of the controller against the process model. The development of the control policies is based on multi-parametric Model Predictive Control (mp-MPC) policies that reduce the online, computational force of the controller by deriving the control inputs as a set of explicit functions of the system states and can be implemented on embedded devices [5]. One of the main advantages of the proposed framework is the ability to test the controllers ‘in-silico’, against the high-fidelity process model and evaluate their performance before operating them online. The results from this study indicate that optimal operation, under maximum purity and productivity yield can be ensured with the development of advanced computational tools. The control policies are applied both in the upstream and the downstream processing; yielding therefore a fertile ground towards the development of a global control strategy that can ensure continuous operation

Operability-economics trade-offs in adsorption-based CO2_2 capture process

Low-carbon dispatchable power underpins a sustainable energy system, providing load balancing complementing wide-scale deployment of intermittent renewable power. In this new context, fossil fuel-fired power plants must be coupled with a post-combustion carbon capture (PCC) process capable of highly transient operation. To tackle design and operational challenges simultaneously, we have developed a computational framework that integrates process design with techno-economic assessment. The backbone of this is a high-fidelity PCC mathematical model of a pressure-vacuum swing adsorption process. We demonstrate that the cost-optimal design has limited process flexibility, challenging reactiveness to disturbances, such as those in the flue gas feed conditions. The results illustrate that flexibility can be introduced by relaxing the CO$_2$ recovery constraint on the operation, albeit at the expense of the capture efficiency of the process. We discover that adsorption-based processes can accommodate for significant flexibility and improved performance with respect to the operational constraints on CO$_2$ recovery and purity. The results herein demonstrate a trade-off between process economics and process operability, which must be effectively rationalised to integrate CO$_2$ capture units in the design of low-carbon energy systems.Comment: Pre-print paper currently under review. 32 pages, 6 figures. The first two authors contributed equally to this wor

Empowering young people who experienced domestic violence and abuse: The development of a group therapy intervention

This article describes the development of a group-based therapeutic intervention for young people (YP) who have lived with domestic violence and abuse. The intervention was informed by interviews with 107 YP, focused on their experiences of coping, resilience and agency. The intervention draws on resources from systemic, creative and narrative approaches to group work, and aims to facilitate YP's expression of distress in a way that recognizes that it is embodied, contextual and relational. The intervention also explores YP's existing strategies for coping and maintaining a sense of agency, and works to harness, enhance and further develop those skills. We report on the pilot of this intervention, and its development and application across four European countries (the United Kingdom, Greece, Italy and Spain). We outline the goals, strengths and limitations of this group intervention, as well as the main challenges, hindrances and ethical dilemmas experienced by the research and intervention team. Implications for therapeutic practice and training are addressed

Evaluation of MMP1 and MMP3 gene polymorphisms in exfoliation syndrome and exfoliation glaucoma

Purpose: To investigate possible genetic associations of matrix metalloproteinase-1 (MMP1) and MMP3 gene polymorphisms with exfoliation syndrome (XFS) with (XFS/+G) and without (XFS/-G) glaucoma in a cohort of Greek patients. Methods: A total of 182 unrelated Greek patients with XFS, including 92 patients with XFS/+G, and 214 unrelated age- and gender-matched controls were enrolled in the study. MMP1-1607 1G/2G (rs1799750) and MMP3-1171 5A/6A (rs3025058) polymorphisms were determined using standard PCR/restriction fragment length polymorphism methods. Differences in allele and genotype distributions were analyzed using logistic regression. Results: The distribution of genotypes and alleles in MMP1 and MMP3 polymorphisms was not significantly different between cases with exfoliation syndrome, with or without glaucoma, and controls. However, the allele contrast for the MMP1 variant showed a trend for a significant association with XFS/-G (Odds Ratio=1.47 [1.03-2.10]), since after correction for multiple comparisons, this association was no longer statistically significant. Conclusions: Our study provided some evidence of a possible role of the MMP1 variant in the development of exfoliation syndrome in Greek patients

Quality of life after stroke: Evaluation of the Greek SAQOL-39g

Background/Aims: Stroke and aphasia rehabilitation aims to improve people’s quality of life. Yet, scales for measuring health-related quality of life in stroke typically exclude people with aphasia. They are also primarily available in English. An exception is the Stroke and Aphasia Quality of Life scale (SAQOL-39g). This scale has been tested with people with aphasia; it has been adapted for use in many countries including Greece. The aim of this study was to examine the psychometric properties of the Greek SAQOL-39g. Methods: An interview-based psychometric study was carried out. Participants completed: receptive sub-tests of Frenchay Aphasia Screening Test, Greek SAQOL-39g, General Health Questionnaire-12, Frenchay Activities Index, Montreal Cognitive Assessment and Barthel Index. Results: 86 people took part; 26 provided test-retest reliability data. The Greek SAQOL-39g demonstrated excellent acceptability (minimal missing data; no floor/ceiling effects), test-retest reliability (ICC= 0.96 scale, 0.83-0.99 domains) and internal consistency (Cronbach’s alpha 0.96 scale, 0.92-0.96 domains). There was strong evidence for convergent (r=0.53-0.80 scale; 0.54-0.89 domains) and discriminant validity (r=0.52 scale; 0.04-0.48 domains). Conclusion: The Greek SAQOL-39g is a valid and reliable scale. It is a promising measure for use in stroke and aphasia treatment prioritization, outcome measurement and service evaluation

The SAGEX Review on Scattering Amplitudes

This is an introduction to, and invitation to read, a series of review articles on scattering amplitudes in gauge theory, gravity, and superstring theory. Our aim is to provide an overview of the field, from basic aspects to a selection of current (2022) research and developments.Comment: 15 pages, overview articl