Chord length distribution based modeling and adaptive model predictive control of batch crystallization processes using high fidelity full population balance models

The control of batch crystallizers is an intensively investigated topic as suitable crystallizer operation can reduce considerably the downstream operation costs and produce crystals of desired properties (size, shape, purity, etc.). Nevertheless, the control of crystallizers is still challenging. In this work the development of a fixed batch time full population balance model based adaptive predictive control system for cooling batch crystallizers is presented. The model equations are solved by the high resolution finite volume algorithm involving fine discretization, which provides a high fidelity, accurate solution. A physically relevant crystal size distribution (CSD) to chord length distribution (CLD) transformation is also developed making possible the direct, real-time application of the focused beam reflectance measurement (FBRM) probe in the control system. The measured CLD and concentration values are processed by the growing horizon estimator (GHE), whose roles are to estimate the unmeasurable system states (CSD) and to readjust the kinetic parameters, providing an adaptive feature for the control system. A repeated sequential optimization algorithm is developed for the nonlinear model predictive control (NMPC) optimization, enabling the reduction of sampling time to the order of minutes for the one-day long batch. According to the simulation results, the strategy is highly robust to parametric plant-model mismatch and significant concentration measurement noise, providing very good control of the desired CLD

Dynamic modelling and nonlinear model predictive control of a fluid catalytic cracking unit

The paper presents the application of two nonlinear model predictive control (NMPC) approaches: quasi-infinite-horizon nonlinear MPC (QIHNMPC) and moving horizon estimator nonlinear MPC (MHE-NMPC) to the Fluid Catalytic Cracking Unit (FCCU). A complex dynamic model of the reactor–regenerator–fractionator system is developed and subsequently used in the controller. The novelty of the model consists in that besides the complex dynamics of the reactor–regenerator system, it also includes the dynamic model of the fractionator, as well as a five lumps kinetic model for the riser. Tight control is achieved using the QIHNMPC approach. The MHE-NMPC considers important features of a real-time control algorithm, resulting in a framework for practical NMPC implementation, such as: state and parameter estimation and efficient solution of the optimisation problem. In the NMPC approach, only measurements available in practice are considered, whereas the rest of the states are estimated together with uncertain model parameters, via MHE technique. Using an efficient numerical implementation based on the multiple shooting algorithm real-time feasibility of the approach is achieved. The incentives of the proposed approaches are assessed on the simulated industrial FCCU

Real time image processing based on-line feedback control system for cooling batch crystallization

The direct nucleation control (DNC) is a process analytical technique (PAT) based model free feedback control strategy for batch and continuous crystallization processes, which has been successfully applied in numerous cases. The basic principle of DNC is the use of controlled dissolution cycles to control a measurement directly related to the particle number in the system. During the DNC, in the case of cooling crystallization fines are dissolved by repeated heating-cooling loops. In this context, the controlled variable is the (relative) particle number, which is manipulated using a feedback control approach through the temperature. The particle number is traditionally measured with focused beam reflectance measurement (FBRM), however other PAT tools can also be employed in a similar feedback control setup. Often crystallization processes are also monitored by real-time imaging systems. In the current work a novel DNC setup is proposed in which microscopy images are captured and processed by the means of image analysis in real time. The images are used to extract the relative particle number, which is controlled using the DNC framework. The robustness of the new image analysis based direct nucleation control (IA-DNC) is presented via three case studies with materials having different crystallization properties. The IA-DNC approach uses a Particle Vision probe although other in situ or in line imaging systems can also be used in the framework. The systems are monitored with FBRM for comparison purposes. The setup achieved stable, converged control in most cases and is demonstrated that the IA-DNC has several advantages over the classical FBRM based DNC. The IA-DNC can also be used for real time feedback control of crystal shape

Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database

BACKGROUND: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression. METHODS: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient's lifetime. RESULTS: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p <  0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p <  0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p <  0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc. CONCLUSIONS: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Objective: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. / Methods: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering. / Results: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. / Conclusion: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis